Glycolysis-dependent sulfur metabolism orchestrates morphological plasticity and virulence in fungi

Growing extra arms or tentacles, changing skin colour or texture – what sounds like the premise of a horror story is actually a common occurrence in nature. Many microscopic fungi can modify their shape to infect hosts and evade their immune defences. These organisms do not simply grow – they can alter their physical form depending on their environment. One moment, they are harmless, yeast-like cells, quietly living in the human gut; the next, they transform into long, thread-like filaments called hyphae that penetrate tissues and cause infections in animals and crops. Scientists call this extraordinary shape-shifting ability ‘fungal morphogenesis’.

While scientists have identified the genes involved in this process, the role of cellular metabolism has been less well established. Previous research suggests that the presence of glucose is important for fungal morphogenesis. But how this sugar influences this shape-shifting behaviour was not completely understood. Understanding what truly controls this process could uncover new ways to prevent harmful fungi from causing diseases in plants and animals.

To determine whether glucose merely supports fungal morphogenesis or truly drives this change, Shah et al. used baker’s yeast and a pathogenic yeast that causes thrush in humans. Both yeast species were grown under nitrogen-limited conditions, a known factor to trigger fungal morphogenesis. When glycolysis - the process that breaks down sugar molecules into energy - was blocked, neither species could shape-shift.

More detailed experiments showed that this was due to the need for glycolysis to produce sulfur-containing building blocks, such as amino acids, that support this transition. When these sulfur-containing building blocks were supplied from the outside, the fungi regained their ability to change shape – even under conditions compromising their ability to perform glycolysis.

This effect was observed in both yeast species, highlighting that this process must be conserved in potentially many yeast species. Blocking glycolysis disarms the pathogen, compromising its morphogenesis and rendering it vulnerable to host defence. This metabolic interference paves the way for a new class of precision antimicrobials that are both more potent in combating infections and less toxic to the infected host. Moreover, fungal morphogenesis has been implicated in causing resistance to existing antifungals. Therefore, targeting glycolysis will support the development of effective therapeutic strategies to increase the efficacy of existing antifungals.

In response to changes in their environment, fungi exhibit remarkable morphological plasticity, allowing them to reversibly transition between specialized cell states. This inherent ability to rapidly adapt to the changes in their environment is essential for their survival and allows them to colonize diverse ecological niches, including various host organisms (Gow et al., 2002; Lin et al., 2015; Naranjo-Ortiz and Gabaldón, 2019). This conserved phenomenon of fungal morphogenesis encompasses a plethora of morphological forms, including pseudohyphae, hyphae, appressoria, and fruiting bodies to name a few (Lin et al., 2015; Riquelme et al., 2018). Importantly, these morphological transitions in various pathogenic fungal species significantly influence their interaction with the respective host, impacting their overall ability to cause persistent infections (Min et al., 2020; Wang and Lin, 2012). Fungal morphogenesis is conserved across a plethora of fungal species and has profound implications with respect to fungal ecology, anti-fungal drug resistance, and pathogenicity across a spectrum of hosts (Christensen, 1989; Puumala et al., 2024; Sexton and Howlett, 2006). Consequently, it has been a central focus of intense scientific investigation over the last several years (Lin et al., 2015; Riquelme et al., 2018). During dimorphic transitions in fungi, changes in cell shape is accompanied by changes in cell polarity, cell size, and cell-cell adhesion, and these changes are regulated by two major signaling pathways: the cAMP-PKA pathway and MAP kinase (MAPK) pathways. Both pathways are crucial for morphogenesis in fungal model systems, including Saccharomyces cerevisiae and Candida albicans. In S. cerevisiae, the cAMP-PKA pathway is a critical regulatory cascade that controls cellular differentiation, such as pseudohyphal growth, in response to glucose availability. The glucose signal is transduced through two parallel mechanisms: the G-protein-coupled receptor (GPCR) Gpr1-Gpa2 system and the intracellular Ras system. The activation of Ras is triggered by high glycolytic flux, which is directly controlled by the Hxt (Hexose Transporter) family dictating the precise rate of glucose import into the cell. Both the Gpr1-Gpa2 and Ras pathways activate the adenylate cyclase (Cyr1), leading to elevated intracellular cAMP levels. This cAMP binds to the regulatory subunit Bcy1, releasing and activating the catalytic Tpk subunits of Protein Kinase A (PKA). This PKA activation, driven primarily by Tpk2, promotes the shift to a filamentous morphology by inducing the expression of necessary genes required for pseudohyphal differentiation (Colombo et al., 1998; Lorenz et al., 2000; Xue et al., 1998). Similarly, this pathway drives the essential yeast to hyphal transition in C. albicans, often via the regulator Efg1 (Maidan et al., 2005). Concurrently, the MAPK (Mitogen-Activated Protein Kinase) pathway operates in parallel to the cAMP-PKA cascade and coordinates fungal morphogenesis in response to extracellular stress and nutrient signals. In S. cerevisiae, the Kss1 cascade is the key effector that drives pseudohyphal growth, predominantly activating under nitrogen-limiting conditions (Lorenz and Heitman, 1998). In the opportunistic fungal pathogen C. albicans, the homologous Cek1 pathway is indispensable for coordinating the complex hyphal development. Cek1 acts as a multifaceted sensor, by processing external morphogenetic cues and often engaging directly with the cell wall integrity system to ensure structural stability during the rapid yeast to hyphal transition. This pathway is a critical determinant of virulence, as its activation promotes the expression of adherence factors and ensures the formation of biofilms, enabling the fungus to colonize host tissues and resist immune response (Csank et al., 1998). The cAMP-PKA and MAPK pathways function in a parallel manner, engaging in significant crosstalk to integrate diverse environmental signals and coordinate a precise morphological response (Biswas et al., 2007; Kumar, 2021). While significant progress has been made in elucidating the intricate gene regulatory networks that govern these morphological transitions (e.g. Genetic networks that orchestrate yeast to pseudohyphal differentiation in S. cerevisiae and yeast to hyphal differentiation in C. albicans have been well characterized [Nantel et al., 2002; Ryan et al., 2012]), a critical knowledge gap persists regarding the underlying metabolic determinants of fungal morphogenesis. Despite the recognized influence of nutrient availability on fungal morphogenesis (Broach, 2012; Fleck et al., 2011; Kumar, 2021), our understanding of the specific metabolic networks and their regulatory influence on morphogenetic switching in fungi remains incompletely characterized.

In this study, we employed S. cerevisiae and the human fungal pathogen, C. albicans, to dissect the metabolic underpinnings of fungal morphogenesis under nitrogen-limiting conditions, a known trigger for morphogenetic switching in these fungi (Csank et al., 1998; Gimeno et al., 1992). Our findings reveal a critical role for central carbon metabolism, particularly glycolysis, in facilitating the yeast to pseudohyphal transition in S. cerevisiae in a cAMP-PKA-independent manner and the yeast to hyphal transition in C. albicans, both of which have been shown to be crucial for their nutrient foraging ability in diverse niches and the ability of C. albicans to successfully infect a host (Palková and Váchová, 2006; Thompson et al., 2011). Comparative transcriptomic analysis identified a conserved metabolic network crucial for these morphogenetic switching events under nitrogen-limiting conditions. Importantly, we observed that perturbations in glycolytic flux using pharmacological and genetic means negatively impact the expression of genes involved in sulfur metabolism. Furthermore, our functional studies demonstrated that supplementation with sulfur-containing amino acids (cysteine or methionine) effectively rescued the morphogenetic defects resulting from glycolytic impairment, establishing a novel metabolic axis linking glycolysis and sulfur metabolism in the regulation of fungal morphogenesis. Finally, we investigated the implications of this glycolysis-dependent sulfur metabolism on the virulence of C. albicans. Our data demonstrate that a C. albicans mutant lacking genes that encode for a crucial glycolytic enzyme, phosphofructokinase-1 (Pfk1), exhibits reduced survival within macrophages and severely attenuated virulence in an in vivo murine model of systemic candidiasis, which is rescued in response to sulfur supplementation to the host.

Collectively, our research, for the first time, identifies a previously uncharacterized metabolic axis linking glycolysis and sulfur metabolism under conditions that induce fungal morphogenesis and underscores the importance of this metabolic network in regulating fungal morphogenesis across two key fungal species and the ability of the human fungal pathogen, C. albicans, to establish infection in a host. These findings address a fundamental knowledge gap in the field and contribute significantly to our understanding of a broadly conserved phenomenon that exists across a plethora of fungal species.

Our findings provide compelling evidence for a conserved metabolic network that intricately links central carbon metabolism (particularly glycolysis), sulfur amino acid biosynthesis, and fungal morphogenesis in both Saccharomyces cerevisiae and Candida albicans. While nitrogen limitation is a well-established and essential trigger for the yeast to pseudohyphae transition in S. cerevisiae, the specific influence of carbon sources on this process has not been completely understood. Studies have shown that fermentable carbon sources are critical for inducing pseudohyphal differentiation under nitrogen-limiting conditions (Van de Velde and Thevelein, 2008). Conversely, when these fermentable sugars are replaced with non-fermentable carbon sources, a significant reduction in pseudohyphal differentiation is observed (Strudwick et al., 2010). These findings collectively suggest that the presence of fermentable carbon sources, and by extension their metabolism, is a critical requirement for inducing fungal morphogenesis in S. cerevisiae. Glucose in the extracellular environment can be sensed by S. cerevisiae using multiple proteins. One such protein is the well-characterized G-protein-coupled receptor (GPCR), Gpr1. Binding of glucose to Gpr1 activates a downstream signalling cascade, resulting in the production of cAMP which activates Protein Kinase A (PKA) (Kraakman et al., 1999; Yun et al., 1997). This glucose-dependent cAMP-PKA pathway has been shown to be essential for pseudohyphal differentiation under nitrogen-limiting conditions (Lorenz et al., 2000). Additionally, a key glycolytic intermediate, fructose-1,6-bisphosphate (FBP), is also known to activate the cAMP-PKA pathway via activation of Ras proteins, further linking glucose metabolism to this crucial signalling cascade (Peeters et al., 2017). However, the role of glucose as a metabolite in the context of pseudohyphal differentiation is not known. Building upon previous data that fermentable carbon sources that are metabolized via glycolysis are able to induce fungal morphogenesis, we asked whether the ability of these cells to undergo active glycolysis is critical for fungal morphogenesis. We took a two-pronged approach which involved pharmacological or genetic perturbation of glycolysis to address this question. Our findings clearly demonstrated that active glycolysis is essential for fungal morphogenesis under nitrogen-limiting conditions. To understand whether the pseudohyphal differentiation defects we observed due to glycolysis perturbation were solely due to the inability of glucose to activate glucose-dependent cAMP-PKA pathway, we performed cAMP add-back assays and interestingly, exogenous supplementation of cAMP failed to rescue pseudohyphal differentiation defects caused by the perturbation of glycolysis (through inhibitors (2DG and NaCi) or through genetic knockout strains (∆∆pfk1 and ∆∆adh1)). Our results clearly demonstrate that the ability of S. cerevisiae to efficiently metabolize glucose via glycolysis is critical for pseudohyphal differentiation under nitrogen-limiting conditions, in a cAMP-PKA-independent manner. This implies that glycolysis may be parallelly regulating other cellular mechanisms essential for this morphological transition. It is plausible that the glycolytic flux, or a yet-to-be-identified downstream intermediate, acts as a distinct metabolic signal that is parallelly important for pseudohyphal differentiation along with the cAMP-PKA pathway. This uncovers a previously unrecognized layer of regulatory complexity in the interplay between central carbon metabolism and fungal morphogenesis.

To gain deeper insights underlying the glycolysis-mediated regulation of fungal morphogenesis in a cAMP-PKA-independent manner, we performed comparative transcriptomics on S. cerevisiae wild-type cells grown under nitrogen-limiting conditions with and without the glycolysis inhibitor, 2DG (which had the strongest inhibitory effect on pseudohyphal differentiation). As anticipated, genes involved in amino acid biosynthesis and transport were upregulated in the 2DG-treated cells, consistent with a feedback response that cells exhibit when glycolysis is perturbed under nitrogen-limiting conditions, as various intermediates of glycolysis are known to serve as precursors for the biosynthesis of several amino acids under these conditions (Dikicioglu et al., 2011; Martíez-Force and Benítez, 1992). Remarkably, we observed a striking and unexpected downregulation of multiple genes specifically involved in the biosynthesis and transport of sulfur-containing amino acids, cysteine and methionine, in the 2DG-treated cells at both early and late time points of pseudohyphal development. This transcriptional downregulation was further validated at the protein level for key proteins involved in the sulfur assimilation pathway (Met4, Met32, Met16, Met10, Cys4, and Cys3), clearly demonstrating the dependence of sulfur metabolism on active glycolysis during fungal morphogenesis. This unexpected link between central carbon metabolism and sulfur metabolism is not restricted to conditions that induce fungal morphogenesis, i.e., in surface-attached colonies grown in nitrogen-limiting conditions, since even in liquid cultures that have limiting levels of nitrogen, wherein S. cerevisiae cells do not undergo pseudohyphal differentiation (Gancedo, 2001; Gimeno et al., 1992), perturbation of glycolysis with 2DG results in significantly reduced expression of proteins involved in the sulfur assimilation pathway (Met32, Met16, Met10, and Cys3).

Given that multiple genes that encode for proteins involved in de novo biosynthesis of sulfur-containing amino acids were downregulated in the presence of 2DG, which strongly inhibits fungal morphogenesis, we wanted to explore the possibility that perturbation of sulfur metabolism is causal for the attenuation of fungal morphogenesis in the presence of 2DG. We tested the functional relevance of this glycolysis-dependent regulation of sulfur metabolism in fungal morphogenesis directly through exogenous supplementation of sulfur sources. Interestingly, cysteine specifically rescued the pseudohyphal differentiation defect exhibited by S. cerevisiae in the presence of 2DG. However, methionine was unable to rescue the pseudohyphal differentiation defect in the presence of 2DG even at various different concentrations (50 µM, 100 µM, 200 µM, and 500 µM). The observed differential rescue effects of cysteine and methionine could be due to the distinct amino acid transport systems used by S. cerevisiae to transport these amino acids. S. cerevisiae primarily uses multiple, low-affinity permeases (Gap1, Bap2, Bap3, Tat1, Tat2, Agp1, Gnp1, and Yct1) for cysteine transport, while relying on a limited set of high-affinity transporters (like Mup1) for methionine transport, with the added complexity that its methionine transporters can also transport cysteine (Düring-Olsen et al., 1999; Huang et al., 2017; Kosugi et al., 2001; Menant et al., 2006). Hence, it is likely that cysteine uptake could be happening at a higher efficiency in S. cerevisiae compared to methionine uptake. Therefore, to achieve a comparable functional rescue by exogenous supplementation of methionine, it is necessary to use a higher concentration of methionine. When we performed our rescue experiments using higher concentrations of methionine, we did not see any rescue of pseudohyphal differentiation in the presence of 2DG, and in fact, we noticed that, at higher concentrations of methionine, the wild-type strain failed to undergo pseudohyphal differentiation even in the absence of 2DG. This is likely due to the fact that increasing the methionine concentration raises the overall nitrogen content of the medium, thereby making the medium less nitrogen-starved. This presents a major experimental constraint, as pseudohyphal differentiation is strictly dependent on nitrogen limitation, and the elevated nitrogen resulting from the higher methionine concentration can inhibit pseudohyphal differentiation. Similarly, gene expression analysis using RT-qPCR revealed a significant downregulation of multiple genes involved in the biosynthesis of sulfur-containing amino acids (met32, met3, met5, and met17) in ∆∆pfk1 and ∆∆adh1 strains and the pseudohyphal differentiation defects observed in these strains were completely rescued by the addition of cysteine or methionine. These findings strongly implicate that de novo biosynthesis of sulfur-containing amino acids is a critical downstream effector of glycolytic activity in promoting pseudohyphal differentiation under nitrogen limitation. To directly assess the role of sulfur metabolism in fungal morphogenesis, we generated and characterized the met32 deletion strain. This particular strain was critical for our investigation because, unlike other MET gene deletions, met32 deletion does not result in auxotrophy for methionine or cysteine. This unique characteristic is attributed to the functional redundancy provided by its paralog, met31 (Blaiseau et al., 1997). The deletion of met32 resulted in substantial defects in pseudohyphal differentiation under nitrogen-limiting conditions, directly implicating the role of sulfur metabolism in regulating fungal morphogenesis. Our sulfur add-back experiments demonstrated that cysteine or methionine rescued the morphogenetic defects exhibited by the met32 knockout strain, further solidifying the direct involvement of sulfur metabolism in this morphogenetic switching process. How active sulfur metabolism contributes towards fungal morphogenesis is not yet understood, but given its critical requirement during this phenomenon, it would be an important question to explore and will further our overall understanding of this important biological phenomenon.

It is interesting to note that the expression of Met4, the principal transcriptional regulator of the de novo biosynthesis of sulfur-containing amino acids in S. cerevisiae, along with Met32, one of its cognate DNA-binding cofactors (Blaiseau et al., 1997), are significantly downregulated when glycolysis is perturbed. Given the obligate requirement of Met4 interaction with DNA-binding proteins, such as Met28, Met32, or Met31, to elicit transcriptional activation of the genes involved in the de novo biosynthesis of sulfur-containing amino acids (Blaiseau and Thomas, 1998), the observed downregulation in both Met4 and Met32 levels likely compromises the overall biosynthesis of sulfur-containing amino acids. This concurrent downregulation could explain the attenuated expression of downstream genes involved in the synthesis of methionine and cysteine. This suggests a novel regulatory mechanism wherein the expression of Met4/Met32 is coupled to glycolytic activity under nitrogen-limiting conditions. Given that sulfur metabolism is coupled to glycolysis in C. albicans as well and contributes towards fungal morphogenesis, it is likely that this conserved regulatory axis might be critical for fungal morphogenesis in a broad range of fungal species. Interestingly, Met4 regulation is directly dependent on Met30 (Rouillon et al., 2000). Met30 functions as a molecular switch for Met4, the master regulator of the MET gene network. Under sulfur-replete conditions, Met30 ensures that Met4 remains inactive through ubiquitination and proteasomal degradation. Conversely, a reduction in sulfur availability diminishes Met30 activity, thereby de-repressing Met4 and allowing it to induce the expression of genes necessary for sulfur amino acid biosynthesis (Rouillon et al., 2000; Smothers et al., 2000; Thomas and Surdin-Kerjan, 1997). Given this regulatory mechanism, we investigated the expression of proteins involved in the sulfur assimilation pathway (Met4, Met32, Met16, and Cys3), in a viable Δmet30 deletion strain, under conditions where glycolysis was perturbed using 2DG. We observed no difference in protein levels of Met4, Met32, Met16, and Cys3, between 2DG-treated and untreated cells. This indicates that, in the heterozygous deletion strain of met30 (∆met30), Met4 is not degraded even when glycolysis is perturbed, supporting the hypothesis that perturbing active glycolysis with inhibitors like 2DG increases Met30 activity, which in turn leads to the increased degradation of Met4, which would then negatively affect MET gene transcription, subsequently attenuating pseudohyphal differentiation. However, a surprising finding emerged when we examined Met30 levels in the presence of 2DG. There was no increase in the levels of Met30 in 2DG-treated cells compared to untreated cells. This suggests that glycolysis influences Met30 activity through a post-translational mechanism, rather than by altering its protein abundance. Studies have shown that under cadmium stress, Met4 activity is upregulated by reducing the activity of Met30 through post-translational events, specifically by inducing the dissociation of Met30 from the core SCF (Skp1/Cullin1/F-box) complex without affecting Met30 protein levels (Lauinger et al., 2024; Yen et al., 2005). This well-established paradigm provides a compelling framework for our observation, suggesting that active glycolytic flux, similar to cadmium stress, might rapidly modulate the activity of Met30 by decreasing its association with the SCF complex to control Met4 activity, rather than through changes in protein synthesis or degradation. Future studies will be needed to delineate the precise post-translational modifications or regulatory interactions that modulate Met30 activity in response to glycolytic flux.

Intriguingly, our work extended these findings to the pathogenic fungus C. albicans, revealing a conserved role for glycolysis-mediated sulfur metabolism in hyphal differentiation, a key virulence attribute in this species (Gow et al., 2011; Moyes et al., 2016; Wilson et al., 2016). Similar to our observations in S. cerevisiae, C. albicans exhibited glycolysis-dependent hyphal formation under nitrogen limitation in a cAMP-PKA-independent manner. Perturbation of glycolysis (either by 2DG addition or the deletion of pfk1) resulted in the significant downregulation of genes involved in de novo biosynthesis of sulfur-containing amino acids (met32, met3, met5 (ecm17), met10 and met17 (met15)) and the hyphal differentiation defects that occur in response to glycolysis perturbation could be rescued by the exogenous supplementation of cysteine or methionine, whereas the exogenous addition of cAMP failed to rescue the hyphal defects caused by the addition of 2DG or the deletion of pfk1. These results clearly demonstrate that de novo biosynthesis of sulfur-containing amino acids is a critical downstream effector of glycolytic activity in promoting hyphal differentiation under nitrogen-limiting conditions in C. albicans as well. Given that central carbon metabolic pathways like glycolysis and sulfur assimilation pathway are broadly conserved metabolic processes across a plethora of fungal species, it is possible that this novel regulatory axis might play a crucial role in modulating fungal morphogenesis in multiple fungal species, and further studies are warranted to explore this. Finally, given the established link between hyphal differentiation and C. albicans virulence, we explored the impact of glycolytic perturbation on the pathogenicity of this fungus. Interestingly, RT-qPCR analysis revealed a significant downregulation of genes involved in hyphal differentiation and virulence (als3, ece1, hwp1, hyr1, ihd1, rbt1, and sap6) upon 2DG treatment and in the ∆∆pfk1 strain. Interestingly, deletions of sugar kinases or transcription factors regulating the expression of glycolysis genes or adh1 in C. albicans leads to filamentation defects and downregulation of filamentation/virulence-specific genes (Askew et al., 2009; Laurian et al., 2019; Song et al., 2019). Our data, showing transcriptional downregulation of hyphal differentiation and virulence genes following glycolytic perturbation via the deletion of pfk1, strongly corroborate these previous findings. This collectively positions glycolysis as a central metabolic nexus, rather than merely a catabolic process, profoundly influencing the pathogenic ability of C. albicans by intricately linking cellular metabolism, morphogenetic transitions, and the expression of its virulence factors. Furthermore, the ∆∆pfk1 strain displayed significantly reduced survival within murine macrophages and attenuated virulence in a murine model of systemic candidiasis, as evidenced by increased host survival, lower kidney fungal burden, and reduced tissue colonization. Remarkably, exogenous sulfur supplementation (N-acetyl cysteine (NAC)) to mice rescued the attenuated virulence exhibited by ΔΔpfk1. It is important to note that, in the context of certain bacterial pathogens, NAC has been reported to augment cellular respiration, subsequently increasing reactive oxygen species (ROS) generation, which contributes to pathogen clearance (Shee et al., 2022). Interestingly, in our study, NAC supplementation to the mice was given prior to the infection and maintained continuously throughout the duration of the experiment. This continuous supply of NAC likely contributes to the rescue of virulence defects exhibited by the ∆∆pfk1 strain. Essentially, NAC likely allows the mutant to fully activate its essential virulence strategies (including morphological switching) to cause a successful infection in the host. These findings underscore the critical role of glycolysis, and by extension, glycolysis-dependent sulfur metabolism, in the virulence of C. albicans.

In conclusion, our study unveils a conserved metabolic network that orchestrates fungal morphogenesis in response to nutrient availability. We demonstrate that active glycolysis, fueled by fermentable carbon sources in a cAMP-PKA-independent manner, plays a crucial role in regulating the de novo biosynthesis of sulfur-containing amino acids in Met30-dependent manner, which in turn are essential for the morphological transitions in both S. cerevisiae and C. albicans (Figure 6). The attenuation of C. albicans virulence upon disruption of this pathway highlights the potential of targeting specific fungal metabolic networks as a novel antifungal strategy. Future research in our laboratory will focus on elucidating the precise molecular mechanisms by which glycolytic intermediates or downstream signals regulate the expression of sulfur metabolism pathway and how sulfur-containing amino acids contribute to the cellular processes underlying fungal morphogenesis.

Figure 6

Download asset Open asset

All relevant data are within the paper and its supporting information files, except for RNA-Seq data and the Whole Genome Sequencing data. RNA-Seq data and the Whole Genome Sequencing data are deposited in NCBI's SRA database and are accessible through BioProject accession number PRJNA1263201. (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1263201).

1. 1. Shah et al.

   (2025) NCBI BioProject

   ID PRJNA1263201. Glycolysis-dependent Sulfur Metabolism Orchestrates Morphological Plasticity and Virulence in Fungi (RNA-Seq and Whole Genome Sequencing).

   https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1263201

1. 1. Askew C
   2. Sellam A
   3. Epp E
   4. Hogues H
   5. Mullick A
   6. Nantel A
   7. Whiteway M

   (2009) Transcriptional regulation of carbohydrate metabolism in the human pathogen Candida albicans

   PLOS Pathogens 5:e1000612.

   https://doi.org/10.1371/journal.ppat.1000612

   • PubMed
   • Google Scholar
2. 1. Bailey DA
   2. Feldmann PJ
   3. Bovey M
   4. Gow NA
   5. Brown AJ

   (1996) The Candida albicans HYR1 gene, which is activated in response to hyphal development, belongs to a gene family encoding yeast cell wall proteins

   Journal of Bacteriology 178:5353–5360.

   https://doi.org/10.1128/jb.178.18.5353-5360.1996

   • PubMed
   • Google Scholar
3. 1. Barford JP
   2. Hall RJ

   (1979) An examination of the Crabtree effect in Saccharomyces cerevisiae: the role of respiratory adaptation

   Journal of General Microbiology 114:267–275.

   https://doi.org/10.1099/00221287-114-2-267

   • Google Scholar
4. 1. Bennetzen JL
   2. Hall BD

   (1982) The primary structure of the Saccharomyces cerevisiae gene for alcohol dehydrogenase

   The Journal of Biological Chemistry 257:3018–3025.

   https://doi.org/10.1016/S0021-9258(19)81067-0

   • PubMed
   • Google Scholar
5. 1. Biswas S
   2. Van Dijck P
   3. Datta A

   (2007) Environmental sensing and signal transduction pathways regulating morphopathogenic determinants of Candida albicans

   Microbiology and Molecular Biology Reviews 71:348–376.

   https://doi.org/10.1128/MMBR.00009-06

   • PubMed
   • Google Scholar
6. 1. Blaiseau PL
   2. Isnard AD
   3. Surdin-Kerjan Y
   4. Thomas D

   (1997) Met31p and Met32p, two related zinc finger proteins, are involved in transcriptional regulation of yeast sulfur amino acid metabolism

   Molecular and Cellular Biology 17:3640–3648.

   https://doi.org/10.1128/MCB.17.7.3640

   • PubMed
   • Google Scholar
7. 1. Blaiseau PL
   2. Thomas D

   (1998) Multiple transcriptional activation complexes tether the yeast activator Met4 to DNA

   The EMBO Journal 17:6327–6336.

   https://doi.org/10.1093/emboj/17.21.6327

   • PubMed
   • Google Scholar
8. 1. Broach JR

   (2012) Nutritional control of growth and development in yeast

   Genetics 192:73–105.

   https://doi.org/10.1534/genetics.111.135731

   • PubMed
   • Google Scholar
9. 1. Chandarlapaty S
   2. Errede B

   (1998) Ash1, a daughter cell-specific protein, is required for pseudohyphal growth of Saccharomyces cerevisiae

   Molecular and Cellular Biology 18:2884–2891.

   https://doi.org/10.1128/MCB.18.5.2884

   • PubMed
   • Google Scholar
10. 1. Chebaro Y
    2. Lorenz M
    3. Fa A
    4. Zheng R
    5. Gustin M

    (2017) Adaptation of Candida albicans to reactive sulfur species

    Genetics 206:151–162.

    https://doi.org/10.1534/genetics.116.199679

    • PubMed
    • Google Scholar
11. 1. Christensen M

    (1989) A view of fungal ecology

    Mycologia 81:1–19.

    https://doi.org/10.1080/00275514.1989.12025620

    • Google Scholar
12. 1. Colombo S
    2. Ma P
    3. Cauwenberg L
    4. Winderickx J
    5. Crauwels M
    6. Teunissen A
    7. Nauwelaers D
    8. de Winde JH
    9. Gorwa MF
    10. Colavizza D
    11. Thevelein JM

    (1998) Involvement of distinct G-proteins, Gpa2 and Ras, in glucose- and intracellular acidification-induced cAMP signalling in the yeast Saccharomyces cerevisiae

    The EMBO Journal 17:3326–3341.

    https://doi.org/10.1093/emboj/17.12.3326

    • PubMed
    • Google Scholar
13. 1. Cramer FB
    2. Woodward GE

    (1952) 2-Desoxy-D-glucose as an antagonist of glucose in yeast fermentation

    Journal of the Franklin Institute 253:354–360.

    https://doi.org/10.1016/0016-0032(52)90852-1

    • Google Scholar
14. 1. Csank C
    2. Schröppel K
    3. Leberer E
    4. Harcus D
    5. Mohamed O
    6. Meloche S
    7. Thomas DY
    8. Whiteway M

    (1998) Roles of the Candida albicans mitogen-activated protein kinase homolog, Cek1p, in hyphal development and systemic candidiasis

    Infection and Immunity 66:2713–2721.

    https://doi.org/10.1128/IAI.66.6.2713-2721.1998

    • Google Scholar
15. 1. De Deken RH

    (1966) The Crabtree effect: a regulatory system in yeast

    Journal of General Microbiology 44:149–156.

    https://doi.org/10.1099/00221287-44-2-149

    • PubMed
    • Google Scholar
16. 1. Deorukhkar SC
    2. Roushani S

    (2017) Virulence traits contributing to pathogenicity of candida species

    Journal of Microbiology & Experimentation 5:e00140.

    https://doi.org/10.15406/jmen.2017.05.00140

    • Google Scholar
17. 1. Dickinson JR
    2. Salgado LEJ
    3. Hewlins MJE

    (2003) The catabolism of amino acids to long chain and complex alcohols in Saccharomyces cerevisiae

    The Journal of Biological Chemistry 278:8028–8034.

    https://doi.org/10.1074/jbc.M211914200

    • PubMed
    • Google Scholar
18. 1. Dikicioglu D
    2. Karabekmez E
    3. Rash B
    4. Pir P
    5. Kirdar B
    6. Oliver SG

    (2011) How yeast re-programmes its transcriptional profile in response to different nutrient impulses

    BMC Systems Biology 5:148.

    https://doi.org/10.1186/1752-0509-5-148

    • PubMed
    • Google Scholar
19. 1. Düring-Olsen L
    2. Regenberg B
    3. Gjermansen C
    4. Kielland-Brandt MC
    5. Hansen J

    (1999) Cysteine uptake by Saccharomyces cerevisiae is accomplished by multiple permeases

    Current Genetics 35:609–617.

    https://doi.org/10.1007/s002940050459

    • PubMed
    • Google Scholar
20. 1. Evans CT
    2. Ratledge C

    (1985) Partial purification and properties of pyruvate kinase and its regulatory role during lipid accumulation by the oleaginous yeast Rhodosporidium toruloides CBS 14

    Canadian Journal of Microbiology 31:479–484.

    https://doi.org/10.1139/m85-089

    • Google Scholar
21. 1. Fleck CB
    2. Schöbel F
    3. Brock M

    (2011) Nutrient acquisition by pathogenic fungi: nutrient availability, pathway regulation, and differences in substrate utilization

    International Journal of Medical Microbiology 301:400–407.

    https://doi.org/10.1016/j.ijmm.2011.04.007

    • PubMed
    • Google Scholar
22. 1. Foy JJ
    2. Bhattacharjee JK

    (1978) Biosynthesis and regulation of fructose-1,6-bisphosphatase and phosphofructokinase in Saccharomyces cerevisiae grown in the presence of glucose and gluconeogenic carbon sources

    Journal of Bacteriology 136:647–656.

    https://doi.org/10.1128/jb.136.2.647-656.1978

    • PubMed
    • Google Scholar
23. 1. Gancedo JM

    (2001) Control of pseudohyphae formation in Saccharomyces cerevisiae

    FEMS Microbiology Reviews 25:107–123.

    https://doi.org/10.1111/j.1574-6976.2001.tb00573.x

    • PubMed
    • Google Scholar
24. 1. Gimeno CJ
    2. Ljungdahl PO
    3. Styles CA
    4. Fink GR

    (1992) Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: regulation by starvation and RAS

    Cell 68:1077–1090.

    https://doi.org/10.1016/0092-8674(92)90079-r

    • PubMed
    • Google Scholar
25. 1. González B
    2. Mas A
    3. Beltran G
    4. Cullen PJ
    5. Torija MJ

    (2017) Role of mitochondrial retrograde pathway in regulating ethanol-inducible filamentous growth in yeast

    Frontiers in Physiology 8:148.

    https://doi.org/10.3389/fphys.2017.00148

    • PubMed
    • Google Scholar
26. 1. Gow NAR
    2. Brown AJP
    3. Odds FC

    (2002) Fungal morphogenesis and host invasion

    Current Opinion in Microbiology 5:366–371.

    https://doi.org/10.1016/s1369-5274(02)00338-7

    • PubMed
    • Google Scholar
27. 1. Gow NAR
    2. van de Veerdonk FL
    3. Brown AJP
    4. Netea MG

    (2011) Candida albicans morphogenesis and host defence: discriminating invasion from colonization

    Nature Reviews. Microbiology 10:112–122.

    https://doi.org/10.1038/nrmicro2711

    • PubMed
    • Google Scholar
28. 1. Harashima T
    2. Heitman J

    (2002) The Galpha protein Gpa2 controls yeast differentiation by interacting with kelch repeat proteins that mimic Gbeta subunits

    Molecular Cell 10:163–173.

    https://doi.org/10.1016/s1097-2765(02)00569-5

    • PubMed
    • Google Scholar
29. 1. Heinisch J

    (1986) Construction and physiological characterization of mutants disrupted in the phosphofructokinase genes of Saccharomyces cerevisiae

    Current Genetics 11:227–234.

    https://doi.org/10.1007/BF00420611

    • PubMed
    • Google Scholar
30. 1. Hirayama T
    2. Miyazaki T
    3. Ito Y
    4. Wakayama M
    5. Shibuya K
    6. Yamashita K
    7. Takazono T
    8. Saijo T
    9. Shimamura S
    10. Yamamoto K
    11. Imamura Y
    12. Izumikawa K
    13. Yanagihara K
    14. Kohno S
    15. Mukae H

    (2020) Virulence assessment of six major pathogenic Candida species in the mouse model of invasive candidiasis caused by fungal translocation

    Scientific Reports 10:3814.

    https://doi.org/10.1038/s41598-020-60792-y

    • PubMed
    • Google Scholar
31. 1. Huang G

    (2012) Regulation of phenotypic transitions in the fungal pathogen Candida albicans

    Virulence 3:251–261.

    https://doi.org/10.4161/viru.20010

    • PubMed
    • Google Scholar
32. 1. Huang CW
    2. Walker ME
    3. Fedrizzi B
    4. Gardner RC
    5. Jiranek V

    (2017) Yeast genes involved in regulating cysteine uptake affect production of hydrogen sulfide from cysteine during fermentation

    FEMS Yeast Research 17:e046.

    https://doi.org/10.1093/femsyr/fox046

    • PubMed
    • Google Scholar
33. 1. Jiménez-López C
    2. Lorenz MC

    (2013) Fungal immune evasion in a model host-pathogen interaction: Candida albicans versus macrophages

    PLOS Pathogens 9:e1003741.

    https://doi.org/10.1371/journal.ppat.1003741

    • PubMed
    • Google Scholar
34. 1. Kaiser P
    2. Sia RAL
    3. Bardes EGS
    4. Lew DJ
    5. Reed SI

    (1998) Cdc34 and the F-box protein Met30 are required for degradation of the Cdk-inhibitory kinase Swe1

    Genes & Development 12:2587–2597.

    https://doi.org/10.1101/gad.12.16.2587

    • Google Scholar
35. 1. Kosugi A
    2. Koizumi Y
    3. Yanagida F
    4. Udaka S

    (2001) MUP1, high affinity methionine permease, is involved in cysteine uptake by Saccharomyces cerevisiae

    Bioscience, Biotechnology, and Biochemistry 65:728–731.

    https://doi.org/10.1271/bbb.65.728

    • PubMed
    • Google Scholar
36. 1. Kraakman L
    2. Lemaire K
    3. Ma P
    4. Teunissen AW
    5. Donaton MC
    6. Van Dijck P
    7. Winderickx J
    8. de Winde JH
    9. Thevelein JM

    (1999) A Saccharomyces cerevisiae G-protein coupled receptor, Gpr1, is specifically required for glucose activation of the cAMP pathway during the transition to growth on glucose

    Molecular Microbiology 32:1002–1012.

    https://doi.org/10.1046/j.1365-2958.1999.01413.x

    • PubMed
    • Google Scholar
37. 1. Kumar A

    (2021) The complex genetic basis and multilayered regulatory control of yeast pseudohyphal growth

    Annual Review of Genetics 55:1–21.

    https://doi.org/10.1146/annurev-genet-071719-020249

    • PubMed
    • Google Scholar
38. 1. Lauinger L
    2. Andronicos A
    3. Flick K
    4. Yu C
    5. Durairaj G
    6. Huang L
    7. Kaiser P

    (2024) Cadmium binding by the F-box domain induces p97-mediated SCF complex disassembly to activate stress response programs

    Nature Communications 15:3894.

    https://doi.org/10.1038/s41467-024-48184-6

    • PubMed
    • Google Scholar
39. 1. Laurian R
    2. Dementhon K
    3. Doumèche B
    4. Soulard A
    5. Noel T
    6. Lemaire M
    7. Cotton P

    (2019) Hexokinase and glucokinases are essential for fitness and virulence in the pathogenic yeast Candida albicans

    Frontiers in Microbiology 10:327.

    https://doi.org/10.3389/fmicb.2019.00327

    • PubMed
    • Google Scholar
40. 1. Laxman S
    2. Tu BP

    (2011) Multiple TORC1-associated proteins regulate nitrogen starvation-dependent cellular differentiation in Saccharomyces cerevisiae

    PLOS ONE 6:e26081.

    https://doi.org/10.1371/journal.pone.0026081

    • PubMed
    • Google Scholar
41. 1. Li DD
    2. Wang Y
    3. Dai BD
    4. Li XX
    5. Zhao LX
    6. Cao YB
    7. Yan L
    8. Jiang YY

    (2013) ECM17-dependent methionine/cysteine biosynthesis contributes to biofilm formation in Candida albicans

    Fungal Genetics and Biology 51:50–59.

    https://doi.org/10.1016/j.fgb.2012.11.010

    • PubMed
    • Google Scholar
42. 1. Lin X
    2. Alspaugh JA
    3. Liu H
    4. Harris S

    (2015) Fungal Morphogenesis

    Cold Spring Harbor Perspectives in Medicine 5:a019679.

    https://doi.org/10.1101/cshperspect.a019679

    • Google Scholar
43. 1. Lionakis MS
    2. Lim JK
    3. Lee CCR
    4. Murphy PM

    (2011) Organ-specific innate immune responses in a mouse model of invasive candidiasis

    Journal of Innate Immunity 3:180–199.

    https://doi.org/10.1159/000321157

    • PubMed
    • Google Scholar
44. 1. Liu Y
    2. Filler SG

    (2011) Candida albicans Als3, a multifunctional adhesin and invasin

    Eukaryotic Cell 10:168–173.

    https://doi.org/10.1128/EC.00279-10

    • PubMed
    • Google Scholar
45. 1. Lobo Z
    2. Maitra PK

    (1983) Phosphofructokinase mutants of yeast

    Biochemistry and Genetics. The Journal of Biological Chemistry 258:1444–1449.

    https://doi.org/10.1016/S0021-9258(18)33006-0

    • PubMed
    • Google Scholar
46. 1. Lorenz MC
    2. Heitman J

    (1997) Yeast pseudohyphal growth is regulated by GPA2, a G protein alpha homolog

    The EMBO Journal 16:7008–7018.

    https://doi.org/10.1093/emboj/16.23.7008

    • PubMed
    • Google Scholar
47. 1. Lorenz MC
    2. Heitman J

    (1998) Regulators of pseudohyphal differentiation in Saccharomyces cerevisiae identified through multicopy suppressor analysis in ammonium permease mutant strains

    Genetics 150:1443–1457.

    https://doi.org/10.1093/genetics/150.4.1443

    • PubMed
    • Google Scholar
48. 1. Lorenz MC
    2. Pan X
    3. Harashima T
    4. Cardenas ME
    5. Xue Y
    6. Hirsch JP
    7. Heitman J

    (2000) The G protein-coupled receptor gpr1 is a nutrient sensor that regulates pseudohyphal differentiation in Saccharomyces cerevisiae

    Genetics 154:609–622.

    https://doi.org/10.1093/genetics/154.2.609

    • PubMed
    • Google Scholar
49. 1. Maidan MM
    2. De Rop L
    3. Serneels J
    4. Exler S
    5. Rupp S
    6. Tournu H
    7. Thevelein JM
    8. Van Dijck P

    (2005) The G protein-coupled receptor Gpr1 and the Galpha protein Gpa2 act through the cAMP-protein kinase A pathway to induce morphogenesis in Candida albicans

    Molecular Biology of the Cell 16:1971–1986.

    https://doi.org/10.1091/mbc.e04-09-0780

    • PubMed
    • Google Scholar
50. 1. Majer O
    2. Bourgeois C
    3. Zwolanek F
    4. Lassnig C
    5. Kerjaschki D
    6. Mack M
    7. Müller M
    8. Kuchler K

    (2012) Type I interferons promote fatal immunopathology by regulating inflammatory monocytes and neutrophils during Candida infections

    PLOS Pathogens 8:e1002811.

    https://doi.org/10.1371/journal.ppat.1002811

    • PubMed
    • Google Scholar
51. 1. Martíez-Force E
    2. Benítez T

    (1992) Changes in yeast amino acid pool with respiratory versus fermentative metabolism

    Biotechnology and Bioengineering 40:643–649.

    https://doi.org/10.1002/bit.260400602

    • PubMed
    • Google Scholar
52. 1. Martin R
    2. Albrecht-Eckardt D
    3. Brunke S
    4. Hube B
    5. Hünniger K
    6. Kurzai O

    (2013) A core filamentation response network in Candida albicans is restricted to eight genes

    PLOS ONE 8:e58613.

    https://doi.org/10.1371/journal.pone.0058613

    • PubMed
    • Google Scholar
53. 1. Masselot M
    2. Robichon-Szulmajster H

    (1975) Methionine biosynthesis in Saccharomyces cerevisiae. I. Genetical analysis of auxotrophic mutants

    Molecular & General Genetics: MGG 139:121–132.

    https://doi.org/10.1007/BF00264692

    • Google Scholar
54. 1. May RC
    2. Casadevall A

    (2018) In fungal intracellular pathogenesis, form determines fate

    mBio 9:e02092-18.

    https://doi.org/10.1128/mBio.02092-18

    • PubMed
    • Google Scholar
55. 1. Menant A
    2. Barbey R
    3. Thomas D

    (2006) Substrate-mediated remodeling of methionine transport by multiple ubiquitin-dependent mechanisms in yeast cells

    The EMBO Journal 25:4436–4447.

    https://doi.org/10.1038/sj.emboj.7601330

    • PubMed
    • Google Scholar
56. 1. Min K
    2. Neiman AM
    3. Konopka JB

    (2020) Fungal Pathogens: Shape-Shifting Invaders

    Trends in Microbiology 28:922–933.

    https://doi.org/10.1016/j.tim.2020.05.001

    • Google Scholar
57. 1. Monniot C
    2. Boisramé A
    3. Da Costa G
    4. Chauvel M
    5. Sautour M
    6. Bougnoux M-E
    7. Bellon-Fontaine M-N
    8. Dalle F
    9. d’Enfert C
    10. Richard ML

    (2013) Rbt1 protein domains analysis in candida albicans brings insights into hyphal surface modifications and rbt1 potential role during adhesion and biofilm formation

    PLOS ONE 8:e82395.

    https://doi.org/10.1371/journal.pone.0082395

    • Google Scholar
58. 1. Moyes DL
    2. Wilson D
    3. Richardson JP
    4. Mogavero S
    5. Tang SX
    6. Wernecke J
    7. Höfs S
    8. Gratacap RL
    9. Robbins J
    10. Runglall M
    11. Murciano C
    12. Blagojevic M
    13. Thavaraj S
    14. Förster TM
    15. Hebecker B
    16. Kasper L
    17. Vizcay G
    18. Iancu SI
    19. Kichik N
    20. Häder A
    21. Kurzai O
    22. Luo T
    23. Krüger T
    24. Kniemeyer O
    25. Cota E
    26. Bader O
    27. Wheeler RT
    28. Gutsmann T
    29. Hube B
    30. Naglik JR

    (2016) Candidalysin is a fungal peptide toxin critical for mucosal infection

    Nature 532:64–68.

    https://doi.org/10.1038/nature17625

    • Google Scholar
59. 1. Nantel A
    2. Dignard D
    3. Bachewich C
    4. Harcus D
    5. Marcil A
    6. Bouin A-P
    7. Sensen CW
    8. Hogues H
    9. van het Hoog M
    10. Gordon P
    11. Rigby T
    12. Benoit F
    13. Tessier DC
    14. Thomas DY
    15. Whiteway M

    (2002) Transcription profiling of Candida albicans cells undergoing the yeast-to-hyphal transition

    Molecular Biology of the Cell 13:3452–3465.

    https://doi.org/10.1091/mbc.e02-05-0272

    • PubMed
    • Google Scholar
60. 1. Naranjo-Ortiz MA
    2. Gabaldón T

    (2019) Fungal evolution: major ecological adaptations and evolutionary transitions

    Biological Reviews of the Cambridge Philosophical Society 94:1443–1476.

    https://doi.org/10.1111/brv.12510

    • PubMed
    • Google Scholar
61. 1. Netea MG
    2. Van Der Graaf CAA
    3. Vonk AG
    4. Verschueren I
    5. Van Der Meer JWM
    6. Kullberg BJ

    (2002) The role of toll-like receptor (TLR) 2 and TLR4 in the host defense against disseminated candidiasis

    The Journal of Infectious Diseases 185:1483–1489.

    https://doi.org/10.1086/340511

    • PubMed
    • Google Scholar
62. 1. Newcomb LL
    2. Diderich JA
    3. Slattery MG
    4. Heideman W

    (2003) Glucose regulation of Saccharomyces cerevisiae cell cycle genes

    Eukaryotic Cell 2:143–149.

    https://doi.org/10.1128/EC.2.1.143-149.2003

    • PubMed
    • Google Scholar
63. 1. Palková Z
    2. Váchová L

    (2006) Life within a community: benefit to yeast long-term survival

    FEMS Microbiology Reviews 30:806–824.

    https://doi.org/10.1111/j.1574-6976.2006.00034.x

    • PubMed
    • Google Scholar
64. 1. Pan X
    2. Harashima T
    3. Heitman J

    (2000) Signal transduction cascades regulating pseudohyphal differentiation of Saccharomyces cerevisiae

    Current Opinion in Microbiology 3:567–572.

    https://doi.org/10.1016/s1369-5274(00)00142-9

    • PubMed
    • Google Scholar
65. 1. Pappas PG
    2. Lionakis MS
    3. Arendrup MC
    4. Ostrosky-Zeichner L
    5. Kullberg BJ

    (2018) Invasive candidiasis

    Nature Reviews. Disease Primers 4:18026.

    https://doi.org/10.1038/nrdp.2018.26

    • PubMed
    • Google Scholar
66. 1. Peeters K
    2. Van Leemputte F
    3. Fischer B
    4. Bonini BM
    5. Quezada H
    6. Tsytlonok M
    7. Haesen D
    8. Vanthienen W
    9. Bernardes N
    10. Gonzalez-Blas CB
    11. Janssens V
    12. Tompa P
    13. Versées W
    14. Thevelein JM

    (2017) Fructose-1,6-bisphosphate couples glycolytic flux to activation of Ras

    Nature Communications 8:922.

    https://doi.org/10.1038/s41467-017-01019-z

    • PubMed
    • Google Scholar
67. 1. Pradhan B
    2. Guha D
    3. Ray P
    4. Das D
    5. Aich P

    (2016) Comparative analysis of the effects of two probiotic bacterial strains on metabolism and innate immunity in the RAW 264.7 murine macrophage cell line

    Probiotics and Antimicrobial Proteins 8:73–84.

    https://doi.org/10.1007/s12602-016-9211-4

    • PubMed
    • Google Scholar
68. 1. Puumala E
    2. Fallah S
    3. Robbins N
    4. Cowen LE

    (2024) Advancements and challenges in antifungal therapeutic development

    Clinical Microbiology Reviews 37:e0014223.

    https://doi.org/10.1128/cmr.00142-23

    • PubMed
    • Google Scholar
69. 1. Reuss O
    2. Vik A
    3. Kolter R
    4. Morschhäuser J

    (2004) The SAT1 flipper, an optimized tool for gene disruption in Candida albicans

    Gene 341:119–127.

    https://doi.org/10.1016/j.gene.2004.06.021

    • PubMed
    • Google Scholar
70. 1. Richardson JP
    2. Mogavero S
    3. Moyes DL
    4. Blagojevic M
    5. Krüger T
    6. Verma AH
    7. Coleman BM
    8. De La Cruz Diaz J
    9. Schulz D
    10. Ponde NO
    11. Carrano G
    12. Kniemeyer O
    13. Wilson D
    14. Bader O
    15. Enoiu SI
    16. Ho J
    17. Kichik N
    18. Gaffen SL
    19. Hube B
    20. Naglik JR

    (2018) Processing of Candida albicans Ece1p Is critical for candidalysin maturation and fungal virulence

    mBio 9:e02178-17.

    https://doi.org/10.1128/mBio.02178-17

    • PubMed
    • Google Scholar
71. 1. Riquelme M
    2. Aguirre J
    3. Bartnicki-García S
    4. Braus GH
    5. Feldbrügge M
    6. Fleig U
    7. Hansberg W
    8. Herrera-Estrella A
    9. Kämper J
    10. Kück U
    11. Mouriño-Pérez RR
    12. Takeshita N
    13. Fischer R

    (2018) Fungal morphogenesis, from the polarized growth of hyphae to complex reproduction and infection structures

    Microbiology and Molecular Biology Reviews 82:e00068.

    https://doi.org/10.1128/MMBR.00068-17

    • PubMed
    • Google Scholar
72. 1. Rolland F
    2. De Winde JH
    3. Lemaire K
    4. Boles E
    5. Thevelein JM
    6. Winderickx J

    (2000) Glucose-induced cAMP signalling in yeast requires both a G-protein coupled receptor system for extracellular glucose detection and a separable hexose kinase-dependent sensing process

    Molecular Microbiology 38:348–358.

    https://doi.org/10.1046/j.1365-2958.2000.02125.x

    • PubMed
    • Google Scholar
73. 1. Rouillon A
    2. Barbey R
    3. Patton EE
    4. Tyers M
    5. Thomas D

    (2000) Feedback-regulated degradation of the transcriptional activator Met4 is triggered by the SCF(Met30 )complex

    The EMBO Journal 19:282–294.

    https://doi.org/10.1093/emboj/19.2.282

    • PubMed
    • Google Scholar
74. 1. Ryan O
    2. Shapiro RS
    3. Kurat CF
    4. Mayhew D
    5. Baryshnikova A
    6. Chin B
    7. Lin ZY
    8. Cox MJ
    9. Vizeacoumar F
    10. Cheung D
    11. Bahr S
    12. Tsui K
    13. Tebbji F
    14. Sellam A
    15. Istel F
    16. Schwarzmüller T
    17. Reynolds TB
    18. Kuchler K
    19. Gifford DK
    20. Whiteway M
    21. Giaever G
    22. Nislow C
    23. Costanzo M
    24. Gingras AC
    25. Mitra RD
    26. Andrews B
    27. Fink GR
    28. Cowen LE
    29. Boone C

    (2012) Global gene deletion analysis exploring yeast filamentous growth

    Science 337:1353–1356.

    https://doi.org/10.1126/science.1224339

    • PubMed
    • Google Scholar
75. 1. Sánchez-Martínez C
    2. Pérez-Martín J

    (2002) Gpa2, a G-protein alpha subunit required for hyphal development in Candida albicans

    Eukaryotic Cell 1:865–874.

    https://doi.org/10.1128/EC.1.6.865-874.2002

    • PubMed
    • Google Scholar
76. 1. Schiestl RH
    2. Gietz RD

    (1989) High efficiency transformation of intact yeast cells using single stranded nucleic acids as a carrier

    Current Genetics 16:339–346.

    https://doi.org/10.1007/BF00340712

    • Google Scholar
77. 1. Schröder M
    2. Chang JS
    3. Kaufman RJ

    (2000) The unfolded protein response represses nitrogen-starvation induced developmental differentiation in yeast

    Genes & Development 14:2962–2975.

    https://doi.org/10.1101/gad.852300

    • Google Scholar
78. 1. Segal E
    2. Frenkel M

    (2018) Experimental in vivo models of candidiasis

    Journal of Fungi 4:21.

    https://doi.org/10.3390/jof4010021

    • PubMed
    • Google Scholar
79. 1. Sexton AC
    2. Howlett BJ

    (2006) Parallels in fungal pathogenesis on plant and animal hosts

    Eukaryotic Cell 5:1941–1949.

    https://doi.org/10.1128/EC.00277-06

    • PubMed
    • Google Scholar
80. 1. Sharkey LL
    2. McNemar MD
    3. Saporito-Irwin SM
    4. Sypherd PS
    5. Fonzi WA

    (1999) HWP1 functions in the morphological development of Candida albicans downstream of EFG1, TUP1, and RBF1

    Journal of Bacteriology 181:5273–5279.

    https://doi.org/10.1128/JB.181.17.5273-5279.1999

    • PubMed
    • Google Scholar
81. 1. Shee S
    2. Singh S
    3. Tripathi A
    4. Thakur C
    5. Kumar T A
    6. Das M
    7. Yadav V
    8. Kohli S
    9. Rajmani RS
    10. Chandra N
    11. Chakrapani H
    12. Drlica K
    13. Singh A

    (2022) Moxifloxacin-mediated killing of Mycobacterium tuberculosis involves respiratory downshift, reductive stress, and accumulation of reactive oxygen species

    Antimicrobial Agents and Chemotherapy 66:e0059222.

    https://doi.org/10.1128/aac.00592-22

    • Google Scholar
82. 1. Shrivastava M
    2. Feng J
    3. Coles M
    4. Clark B
    5. Islam A
    6. Dumeaux V
    7. Whiteway M

    (2021) Modulation of the complex regulatory network for methionine biosynthesis in fungi

    Genetics 217:iyaa049.

    https://doi.org/10.1093/genetics/iyaa049

    • PubMed
    • Google Scholar
83. 1. Smith MG
    2. Des Etages SG
    3. Snyder M

    (2004) Microbial synergy via an ethanol-triggered pathway

    Molecular and Cellular Biology 24:3874–3884.

    https://doi.org/10.1128/MCB.24.9.3874-3884.2004

    • PubMed
    • Google Scholar
84. 1. Smothers DB
    2. Kozubowski L
    3. Dixon C
    4. Goebl MG
    5. Mathias N

    (2000) The abundance of Met30p limits SCF(Met30p) complex activity and is regulated by methionine availability

    Molecular and Cellular Biology 20:7845–7852.

    https://doi.org/10.1128/MCB.20.21.7845-7852.2000

    • PubMed
    • Google Scholar
85. 1. Song Y
    2. Li S
    3. Zhao Y
    4. Zhang Y
    5. Lv Y
    6. Jiang Y
    7. Wang Y
    8. Li D
    9. Zhang H

    (2019) ADH1 promotes Candida albicans pathogenicity by stimulating oxidative phosphorylation

    International Journal of Medical Microbiology 309:151330.

    https://doi.org/10.1016/j.ijmm.2019.151330

    • PubMed
    • Google Scholar
86. 1. Strudwick N
    2. Brown M
    3. Parmar VM
    4. Schröder M

    (2010) Ime1 and Ime2 are required for pseudohyphal growth of Saccharomyces cerevisiae on nonfermentable carbon sources

    Molecular and Cellular Biology 30:5514–5530.

    https://doi.org/10.1128/MCB.00390-10

    • PubMed
    • Google Scholar
87. 1. Su NY
    2. Ouni I
    3. Papagiannis CV
    4. Kaiser P

    (2008) A dominant suppressor mutation of the met30 cell cycle defect suggests regulation of the Saccharomyces cerevisiae Met4-Cbf1 transcription complex by Met32

    The Journal of Biological Chemistry 283:11615–11624.

    https://doi.org/10.1074/jbc.M708230200

    • PubMed
    • Google Scholar
88. 1. Su C
    2. Yu J
    3. Sun Q
    4. Liu Q
    5. Lu Y

    (2018) Hyphal induction under the condition without inoculation in Candida albicans is triggered by Brg1-mediated removal of NRG1 inhibition

    Molecular Microbiology 108:410–423.

    https://doi.org/10.1111/mmi.13944

    • PubMed
    • Google Scholar
89. 1. Thomas D
    2. Surdin-Kerjan Y

    (1997) Metabolism of sulfur amino acids in Saccharomyces cerevisiae

    Microbiology and Molecular Biology Reviews 61:503–532.

    https://doi.org/10.1128/.61.4.503-532.1997

    • Google Scholar
90. 1. Thompson DS
    2. Carlisle PL
    3. Kadosh D

    (2011) Coevolution of morphology and virulence in Candida species

    Eukaryotic Cell 10:1173–1182.

    https://doi.org/10.1128/EC.05085-11

    • PubMed
    • Google Scholar
91. 1. Uwamahoro N
    2. Verma-Gaur J
    3. Shen HH
    4. Qu Y
    5. Lewis R
    6. Lu J
    7. Bambery K
    8. Masters SL
    9. Vince JE
    10. Naderer T
    11. Traven A

    (2014) The pathogen Candida albicans hijacks pyroptosis for escape from macrophages

    mBio 5:e00003-14.

    https://doi.org/10.1128/mBio.00003-14

    • PubMed
    • Google Scholar
92. 1. Van de Velde S
    2. Thevelein JM

    (2008) Cyclic AMP-protein kinase A and Snf1 signaling mechanisms underlie the superior potency of sucrose for induction of filamentation in Saccharomyces cerevisiae

    Eukaryotic Cell 7:286–293.

    https://doi.org/10.1128/EC.00276-07

    • PubMed
    • Google Scholar
93. 1. Wang L
    2. Lin X

    (2012) Morphogenesis in fungal pathogenicity: shape, size, and surface

    PLOS Pathogens 8:e1003027.

    https://doi.org/10.1371/journal.ppat.1003027

    • PubMed
    • Google Scholar
94. 1. Wilson D
    2. Naglik JR
    3. Hube B

    (2016) The missing link between candida albicans hyphal morphogenesis and host cell damage

    PLOS Pathogens 12:e1005867.

    https://doi.org/10.1371/journal.ppat.1005867

    • PubMed
    • Google Scholar
95. 1. Winer J
    2. Jung CK
    3. Shackel I
    4. Williams PM

    (1999) Development and validation of real-time quantitative reverse transcriptase-polymerase chain reaction for monitoring gene expression in cardiac myocytes in vitro

    Analytical Biochemistry 270:41–49.

    https://doi.org/10.1006/abio.1999.4085

    • PubMed
    • Google Scholar
96. 1. Wu J
    2. Zhang N
    3. Hayes A
    4. Panoutsopoulou K
    5. Oliver SG

    (2004) Global analysis of nutrient control of gene expression in Saccharomyces cerevisiae during growth and starvation

    PNAS 101:3148–3153.

    https://doi.org/10.1073/pnas.0308321100

    • Google Scholar
97. 1. Wu Y
    2. Zhang S
    3. Gong X
    4. Yu Q
    5. Zhang Y
    6. Luo M
    7. Zhang X
    8. Workman JL
    9. Yu X
    10. Li S

    (2019) Glycolysis regulates gene expression by promoting the crosstalk between H3K4 trimethylation and H3K14 acetylation in Saccharomyces cerevisiae

    Journal of Genetics and Genomics 46:561–574.

    https://doi.org/10.1016/j.jgg.2019.11.007

    • PubMed
    • Google Scholar
98. 1. Xue Y
    2. Batlle M
    3. Hirsch JP

    (1998) GPR1 encodes a putative G protein-coupled receptor that associates with the Gpa2p Galpha subunit and functions in a Ras-independent pathway

    The EMBO Journal 17:1996–2007.

    https://doi.org/10.1093/emboj/17.7.1996

    • PubMed
    • Google Scholar
99. 1. Yen JL
    2. Su NY
    3. Kaiser P

    (2005) The yeast ubiquitin ligase SCFMet30 regulates heavy metal response

    Molecular Biology of the Cell 16:1872–1882.

    https://doi.org/10.1091/mbc.e04-12-1130

    • PubMed
    • Google Scholar
100. 1. Yoshino M
     2. Murakami K

     (1982) AMP deaminase as a control system of glycolysis in yeast: Mechanism of the inhibition of glycolysis by fatty acid and citrate

     The Journal of Biological Chemistry 257:10644–10649.

     https://doi.org/10.1016/S0021-9258(18)33871-7

     • PubMed
     • Google Scholar
101. 1. Yun CW
     2. Tamaki H
     3. Nakayama R
     4. Yamamoto K
     5. Kumagai H

     (1997) G-protein coupled receptor from yeast Saccharomyces cerevisiae

     Biochemical and Biophysical Research Communications 240:287–292.

     https://doi.org/10.1006/bbrc.1997.7649

     • PubMed
     • Google Scholar

Author details

1. Dhrumi Shah

   1. CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India
   2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India

   Contribution

   Conceptualization, Formal analysis, Investigation, Visualization, Writing – original draft

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0009-0005-9108-3933

2. Nikita Rewatkar

   CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India

   Contribution

   Investigation

   Competing interests

   No competing interests declared

3. Adishree M

   CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India

   Contribution

   Investigation

   Competing interests

   No competing interests declared

4. Siddhi Gupta

   1. CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India
   2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India

   Contribution

   Investigation

   Competing interests

   No competing interests declared

5. Sudharsan Mathivathanan

   CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India

   Contribution

   Investigation

   Competing interests

   No competing interests declared

6. Sayantani Biswas

   CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India

   Contribution

   Investigation

   Competing interests

   No competing interests declared

7. Sriram Varahan

   CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India

   Contribution

   Conceptualization, Formal analysis, Supervision, Funding acquisition, Investigation, Visualization, Writing – original draft, Writing – review and editing

   For correspondence

   sriram.ccmb@csir.res.in

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-3609-4032

• 679

  views

• 31

  downloads

• 0

  citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.