Yeast are microscopic fungi that are found on many plants, in the soil and in other environments around the world. But, when given the chance, some yeasts are also good at infecting human and other animals and causing disease.

It has been proposed that some opportunistic microbes may have dual-use traits that evolved for one purpose in their natural environment but also incidentally allow them to infect animals. For example, a toxin that helps the opportunistic microbe compete against neighboring microbes may also weaken an animal. Or the ability of many individual microbe cells to clump together into structures known as biofilms on solid surfaces, or floating mats called flors on liquids, helps them to survive in harsh environments, whether in the soil or in the body of an animal.

To investigate this possibility, Ekdahl, Salcedo et al. examined whether artificially selecting yeast with a specific trait – the ability to stick to plastic beads – in the absence of any host animals would inadvertently also select for yeast that were good at causing disease. This trait was selected because it has not been previously linked to opportunistic yeast infections.

The team grew the yeast for 400 generations in tubes that each contained a plastic bead. At every generation, only yeast that stuck to the plastic bead were transferred to a fresh tube to grow the next generation. The experiments found that, not only did the ability of the yeast to stick to the plastic increase over time, but the yeast also evolved the ability to form biofilms and flors. Furthermore, the sticky yeast killed an insect host known as wax moth larvae more quickly than non-sticky yeast.

Together, these findings demonstrate that when microbes evolve in an environment that is devoid of any host animals, selection can inadvertently favor dual-use traits that also help the yeast to infect animals. Opportunistic yeast infections are of increasing concern in human patients, particularly those with weakened immune systems. Understanding which yeast traits are dual-use will help guide future efforts in combatting yeast and other opportunistic microbes.

The study of infectious disease often focuses on pathogenic microbes that either specialize in exploiting animal hosts or act as commensals that switch to pathogenesis when the delicate balance between host and microbe is perturbed. These microbes are presumed to have co-evolved complex adaptations that allow survival and reproduction in and on hosts. However, there exists a broad range of microbial organisms that live in the open environment (i.e. soil, vegetation, aquatic habitats) that are capable of causing disease when the opportunity presents itself (Brown et al., 2012). Such microbes also have adaptations that allow host exploitation, but the origin of these adaptations is unclear, as growth and survival in a host is not a required part of the lifecycle (Casadevall and Pirofski, 2007). For example, the soil-associated bacteria Pseudomonas aeruginosa (Selezska et al., 2012) and Burkholderia cepacia (Mahenthiralingam et al., 2008) can infect the lungs of cystic fibrosis patients.

The existence of virulence traits in environmentally-derived opportunistic pathogens may be due to selection favoring the traits for other uses in the non-host environment, which challenges the idea that co-evolution is a requirement of microbial pathogenesis and virulence. This hypothesis, first proposed and explored in the bacterial literature, is known as ‘coincidental selection’ (Levin and Svanborg Edén, 1990). Much of the research testing the coincidental selection hypothesis has focused on the biotic environment as a selective pressure, specifically the role of predatory bacteriophages and protists (reviewed in [Sun et al., 2018; Davies et al., 2016; Erken et al., 2013]). The relationship between virulence, bacteria, and their predators is complex (Brüssow, 2007). For example, a positive relationship between amoeba predation and virulence was shown in Escherichia coli (Adiba et al., 2010), while selection by amoeba predation led to a decrease virulence in P. aeruginosa (Leong et al., 2022). In the same bacterial species, an evolution experiment with both protist and phage predators showed that phage could mitigate the decrease in virulence associated with protist predation (Friman and Buckling, 2014). Despite the complexity, it is clear that selection from the biotic environment can strongly influence bacterial virulence.

A hypothesis similar to coincidental selection, known as ‘accidental virulence’, has been proposed (Casadevall and Pirofski, 2007) and explored in parallel in the eukaryotic microbial literature, also with a focus on the biotic environment (reviewed in Siscar-Lewin et al., 2022; Casadevall et al., 2019). For example, in the fungus Cryptococcus neoformans, traits that protect from predatory amoeba also play a role in human infection (Steenbergen et al., 2001), and selection by amoeba can increase the prevalence of such traits (Fu et al., 2021; Steenbergen et al., 2003). Similarly, co-culturing Paracoccidioides fungi with amoeba can lead to increased virulence (Albuquerque et al., 2019).

In both the bacterial and eukaryotic literature, there has been less focus on the role of selection imposed by the abiotic environment, although temperature is increasingly a consideration, as thermotolerance and halotolerance may make colonization in and on humans more likely (Casadevall, 2020; Garcia-Solache and Casadevall, 2010). For example, the emerging opportunistic yeast Candida auris, which is found in warm and salty coastal wetlands, can cause severe systemic infection (Arora et al., 2021). There is also experimental evidence that increased temperature can select for virulence in P. aeruginosa (Friman et al., 2011).

The dual-use virulence traits that can be under ‘coincidental selection’ and lead to ‘accidental virulence’ are numerous and range from toxin production, such as the production of gliotoxin in the soil-dwelling filamentous fungus Aspergillus fumigatus (Hillmann et al., 2015; Gupta et al., 2021), to protective structures, such as capsule formation in C. neoformans (Casadevall et al., 2003). Another type of trait, which is the focus of the research presented here, is adherence. Adherence is important for many microbial behaviors required for survival (e.g., biofilm formation) (West et al., 2007), but can also play a role in pathogenicity and virulence (Douglas, 2003; Hall-Stoodley et al., 2004). The ability to adhere to and invade tissues, as well as form communities resistant to anti-microbials, can be key to successful pathogenicity. In the soil-associated yeast, Blastomyces dermatitidis (Baumgardner and Laundre, 2001), which can cause lung infections, the deletion of a single adhesin gene abolishes pathogenesis (Klein, 2000).

The function of microbial traits in both the open environment and the host is crucial evidence for the coincidental selection-accidental virulence hypothesis. However, experimental evolution allows the idea to be tested directly; thus far, most evolution experiments have focused on co-culturing opportunistic microbes with predators (e.g., [Leong et al., 2022; Friman and Buckling, 2014; Fu et al., 2021; Steenbergen et al., 2003; Albuquerque et al., 2019; Friman et al., 2011; Mikonranta et al., 2012; Hosseinidoust et al., 2013]). In the research presented here, rather than altering the biotic or abiotic environment and determining the effect on virulence, we apply direct selection to a specific trait hypothesized to be dual-use in the biomedical model yeast Saccharomyces cerevisiae.

Aside from serving as a model for genetics and cell biology, and being found in a myriad of ecological niches around the globe (Peter et al., 2018), S. cerevisiae is also an opportunistic pathogen capable of infecting immunocompromised individuals, with reports of infections increasing (Aucott et al., 1990; Muñoz et al., 2005; Llopis et al., 2014; Enache-Angoulvant and Hennequin, 2005; Hennequin et al., 2000; Pérez-Torrado and Querol, 2015). As such, it has been a model for fungal pathogenesis-related traits (Clemons et al., 1994; Fraser et al., 2012; McCusker et al., 1994a; Phadke et al., 2018). Some environmentally derived strains are capable of adhering to surfaces and expressing associated aggregative phenotypes (Verstrepen and Klis, 2006). These range from biofilms on solid and semi-solid agar, to pseudohyphal growth and agar invasion, to floating mats on liquid surfaces (flors). Of these multicellular phenotypes, only invasive and pseudohyphal growth have been linked to pathogenicity in S. cerevisiae (McCusker et al., 1994a; Phadke et al., 2018; Palecek et al., 2002), although biofilm formation has been linked to pathogenicity in other fungi (Fanning and Mitchell, 2012). Not all strains are capable of expressing these phenotypes. And while some strains express multiple multicellular traits (Casalone et al., 2005; Zara et al., 2009), there does not appear to be a correlation among the numerous adherence phenotypes (Hope and Dunham, 2014). Despite overlap in conserved signaling and regulatory networks governing the traits, the ability of a strain to express multicellularity in one form does not necessarily suggest the ability to express it in another (Cullen and Sprague, 2012). This is not entirely surprising, since different environmental conditions likely favor different multicellular phenotypes.

Here, yeast populations were artificially selected for adherence ability in one context, in order to determine whether it led to an increase in virulence in another. Specifically, yeast were evolved to adhere to a plastic bead (Poltak and Cooper, 2011), then tested against wax moth larvae to estimate virulence. In replicate populations of two genetic backgrounds, the yeast increased in their ability to express multicellularity in numerous forms. Not all multicellular phenotypes responded in the same way, with pseudohyphal growth appearing to evolve independently from plastic adherence, biofilm formation, and flor formation. This phenotypic evolution demonstrates the complexity of the interacting genetic networks underlying yeast multicellularity. Along with these correlated effects of selection, the yeast also became more virulent. Our results experimentally demonstrate that selection on dual-use traits outside of a host environment can inadvertently favor pre-adaptations for virulence.

The evolution experiment was conducted in two genetic backgrounds. While most S. cerevisiae strains can be pathogenic against wax moth larvae if administered with a high enough inoculum (Phadke et al., 2018), we chose two strains isolated from clinical settings, and therefore, had a known tendency toward human pathogenicity as well. These strains were highly heterozygous, with tens of thousands of SNPs in each genome (Magwene et al., 2011); thus, the strains contained standing genetic variation on which selection could act. The first strain, YJM311, was isolated from the bile tube of a patient in San Francisco in 1981 (McCusker et al., 1994b); its recombinant offspring vary in at least one form of filamentous growth (Lenhart et al., 2019). The second strain, YJM128, was isolated from the lung of a patient in Missouri in the 1980s (Tawfik et al., 1989). Both strains were engineered to constitutively express mCherry, then sporulated, digested, and germinated. Each pool of recombinant offspring was used to inoculate replicate populations.

From each ancestral strain, 10 replicate populations were evolved via serial transfer for 350–400 mitotic generations, half punctuated with sexual cycles every 40 generations, and two without beads as controls. YJM311 was evolved for 8 sexual cycles, while YJM128 was evolved for 9. Populations were grown in limiting medium in glass tubes in the presence of a plastic bead (Figure 1A–B). After growth, beads were washed, suspended in water, and sonicated to detach cells. The cell suspension was transferred to the next tube for growth (Figure 1—figure supplement 1). In YJM128, the sexual control failed to propagate after the first cycle. Therefore, a full complement of controls (three asexual and three sexual) were subsequently initiated and evolved in the same manner.

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Figure 1—source data 1

Counts of cells that adhered to plastic beads grown with replicate populations at different timepoints from YJM311/HMY7-derived populations.

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Figure 1—source data 2

Counts of cells that adhered to plastic beads grown with replicate populations at different timepoints from YJM128/HMY355-derived populations.

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The number of cells attaching to the bead increased over time in the experimental populations (Figure 1; Supplementary file 1c). The data were analyzed with a linear mixed-effect model (LMM); coefficients for the treatment x cycle interaction estimate the effect a given treatment had over time on the number of cells adhering to a bead, as measured by hemocytometer counts. In both genetic backgrounds, the interaction coefficients were positive and sexual populations showed a larger effect than the asexual (YJM311, asexual*cycle = 0.054 (confidence interval ± 0.048), sexual*cycle = 0.184 (±0.048); YJM128, asexual*cycle = 0.47 (±0.242), sexual*cycle = 0.598 (±0.254)). Hence, as has been demonstrated in other evolution experiments in microorganisms (Zeyl and Bell, 1997; Goddard et al., 2005; McDonald et al., 2016; Kosheleva and Desai, 2018; Kaltz and Bell, 2002; Lachapelle and Bell, 2012), sexual populations showed increased adaptation in comparison to asexual populations.

In order to interrogate other effects of adherence selection, at the end of the experiment, ten individual clones were isolated from each population from four timepoints (for YJM311, cycles 2, 4, 6, 8, and for YJM128, cycles 1, 3, 6, 9). For each genetic background, over 400 clones, along with 20 ancestral recombinant offspring, were arrayed in a 96-well plate format for analysis of multicellular phenotypes.

Plastic adherence ability

The panel of clones was first assayed for plastic adherence ability (Figure 2A with Figure 2—figure supplements 1 and 2). Plastic adherence was measured with a microplate reader that detected the fluorescence signal of cells remaining attached to a well in which culture was grown to saturation and gently rinsed. As expected, plastic adherence increased over time in the clones from experimental populations (YJM311: control*cycle = 0.008 (±0.056), asexual*cycle = 0.040 (±0.040), sexual*cycle = 0.100 (±0.040); YJM128: control*cycle = 0.016 (±0.076), asexual*cycle = 0.012 (±0.102); sexual*cycle = 0.187 (±0.114); Supplementary file 1d). Fluorescent signal could have evolved over the course of the experiment; indeed, from the beginning, YJM128 produced a brighter fluorescent signal than YJM311, suggesting the existence of genetic variants that could influence fluorescence expression. Despite the potential for noise in the measurement, the signal of increased adherence throughout the experiment was apparent in both genetic backgrounds. These clonal data support the results of the whole-population adherence measurement (Figure 1), in which cells attaching to a plastic bead were counted manually with a hemocytometer.

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Plastic adherence, biofilm, flor, and PSH measurements for ancestor and evolved clones from the YJM311/HMY7-derived replicate populations.

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Plastic adherence, biofilm, flor, and PSH measurements for ancestor and evolved clones from the YJM/128HMY355-derived replicate populations.

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We next measured the ability of the clonal panel to express three other seemingly different multicellular phenotypes.

Hyper-multicellularity

To understand the phenotypic landscape of the evolved populations and to determine whether the different forms of multicellularity evolved in concert in individual clones, the clonal phenotype data were combined in a principal components analysis (PCA) (Figure 3 with supplements 1 and 2). In YJM311, the loadings of the first two components, which explain 78% of the variation, show that evolved clones with the most extreme values of plastic adherence and flor formation do not tend to also excel at PSH. There were clones, however, that evolved to excel in all of the phenotypes, while not obtaining the most extreme values of the individual traits. In YJM128, the first two loadings explain 70% of the variation, and again, PSH appeared separated from the other multicellular phenotypes. Individual correlations between traits bear out this interpretation (Figure 3—figure supplements 3 and 4). When grouped by experimental treatments, clones from control, asexual, and sexual populations tended to occupy their own, somewhat overlapping, phenotypic space.

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Survival data for wax moth larvae injected with strains from YJM311/HMY7-derived populations.

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Survival data for wax moth larvae injected with strains from YJM128/HMY355-derived populations.

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In both backgrounds, as the populations evolved, there were individual clones that increased in all abilities, and became ‘hyper-multicellular’. Thus, a simple process of selection for plastic adherence led to correlated effects in multiple multicellular traits. These correlated effects were apparent both at the population-level, with mean phenotypes increasing in populations over the generations, but also at the individual-level with the evolution of hyper-multicellularity.

FLO11 length variation

One possible explanation for the increase in multiple forms of multicellularity is a change in a genetic element common to all four phenotypes. A genome-wide investigation into the genetic basis of three multicellular phenotypes (biofilm formation, PSH, and invasive growth) in a lab strain of S. cerevisiae found that each phenotype appeared to have its own set of hundreds of genes underlying its expression, but also some overlap in select transcription factors and signaling pathways (Ryan et al., 2012). Notably, the one element that all of the traits had in common, as do other aggregative phenotypes, is the requirement of the cell adhesin, Flo11p (Reynolds and Fink, 2001; Zara et al., 2005; Lo and Dranginis, 1998), which allows yeast cells to adhere to surfaces and other cells (Dranginis et al., 2007).

Flo11p is a cell surface protein with three domains: a C-terminal that facilitates attachment to the cell wall, an exposed N-terminal immunoglobulin-like domain that mediates cell adhesion (Kraushaar et al., 2015), and a low-complexity, serine-threonine rich B-domain of variable length that extends the adhesion domain away from the cell (Dranginis et al., 2007). The tandem repeats in the B-domain have been shown to be unstable (Fidalgo et al., 2006; Fidalgo et al., 2008) and to vary in length naturally (Zara et al., 2009; Oppler et al., 2019; David-Vaizant and Alexandre, 2018; Verstrepen et al., 2005). Differences in the length of this repetitive region have been shown to affect the strength of multicellular phenotypes in some genetic backgrounds (Zara et al., 2009; Fidalgo et al., 2008).

To determine whether FLO11 length changed throughout the experiment, amplicons of the gene were analyzed with electrophoresis in a subset of clones from the final timepoint (Figure 4). In the YJM311 populations, five out of eight experimental populations ended with an approximate 1000 bp length increase in some or all clones, while none of the control clones showed an increase in length. It is unknown whether the change in length was due to independent de novo mutations or selection favoring an existing allele. The similar allelic length in multiple replicate populations favors the latter explanation. It is possible that during the generation of the starting recombinant pool, there was a mutation that was not detected in the subset of ancestral clones later chosen for analysis. In this genetic background, FLO11 length is not correlated with the strength of plastic adherence, nor with the other three multicellular phenotypes (Figure 4—figure supplement 1).

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In YJM128, the ancestral pool likely had two alleles separated by a few hundred basepairs. The ending asexual populations appeared to have these alleles, with one much longer allele in a clone in one replicate. The ending sexual populations contained the ancestral alleles, as well as other variants both longer and shorter. Clones from one replicate could not be amplified (Sa), suggesting the possibility of a mutation in the region where the primers anneal. Again, FLO11 length was not correlated with the strength of plastic adherence, nor with the other three multicellular phenotypes (Figure 4—figure supplement 2).

Thus, while FLO11 length evolved during the experiment, it does not appear to be the cause of the correlated response to selection on adherence. However, this does not rule out the possibility that FLO11 plays a role. It is possible that expression of the gene, through its complex regulatory network (Rupp et al., 1999; Octavio et al., 2009; Bumgarner et al., 2009), is related to the phenotypic response to adherence selection.

Virulence

To test the coincidental selection-accidental virulence hypothesis, we sought to determine if the evolved changes had an effect on virulence, and were particularly interested in the unexpected evolution of hyper-multicellular clones. Virulence was measured using larvae of the greater wax moth, Galleria mellonella, an invertebrate model used to study microbial pathogenesis and virulence (Pereira et al., 2018), including in S. cerevisiae (Phadke et al., 2018). Using the phenotyping data and the PCA results as a guide, for each genetic background, we identified six hyper-multicellular clones and six non-multicellular clones (Figure 5, Supplementary file 1a, b). We attempted to identify evolved clones that excelled in all measured aggregative traits; therefore, not all were from the final time point, but all were from late in the experiment. In choosing the non-multicellular strains, clones were taken from a variety of time points, including the ancestor, control, and experimental populations at different time points. This allowed us to verify that it was the evolved hyper-multicellular phenotype and not just long-term growth in the evolution medium.

Figure 5

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Strains were grown in the medium in which they were evolved, then washed, adjusted for density, and injected into larvae. Larval survival and pupation were monitored for the next 7 days. Different batches of larvae can be variable in their response to microbial insult; therefore, to ensure reproducibility of results, the experiment was repeated multiple times with numerous batches of larvae, with each batch being challenged by all strains from a genetic background. For the clones derived from YM311, of the 2400 larvae injected with yeast, 1809 did not survive through day 7. Larvae injected with a hyper-multicellular strain were 1.28 times more likely to die than those injected with a non-multicellular strain (mixed effects Cox model: coefficient = 0.249, coeff. s.e. = 0.068, p<0.001) (Figure 5). For the clones derived from YM128, of the 2160 larvae injected with yeast, 1113 did not survive through day 7. Larvae injected with a hyper-multicellular strain were 1.29 times more likely to die than those injected with a non-multicellular strain (coefficient = 0.251, coeff. s.e. = 0.117, p=0.032) (Figure 5). When considering the survival curves of individual strains, non-multicellular strains were less virulent regardless of whether they were from ancestral, control or experimental populations.

Thus, the evolutionary changes brought about by selection for adherence to a plastic bead, led to the incidental evolution of increased virulence.

Our results demonstrate that selection on one yeast trait can generate a correlated response in other traits— a common feature of organismal evolution (Price and Langen, 1992)— but here, the correlated traits may have included those associated with virulence. In this experiment, favoring the ability to adhere to plastic, a surface that is common in industrial, medical, and domestic settings (Geyer et al., 2017), led to a suite of aggregative phenotypes and increased virulence.

The coincidental selection-accidental virulence hypothesis proposes that selection for survival in harsh conditions may lead to traits that predispose microbes to virulence. However, harsh environmental conditions can also favor traits that favor the collective, or multicellular phenotypes (Tong et al., 2022), so it is perhaps not surprising that other forms of multicellularity increased throughout this experiment. Furthermore, in its long evolutionary history, S. cerevisiae has evolved the genetic capability to express multiple different multicellular phenotypes, most of which are induced in nutrient limiting conditions; the experiment presented here was performed in such conditions (glucose limited medium). Other experiments with yeast growing in nutrient limiting conditions have resulted in the unintended evolution of single aggregative behaviors (Hope et al., 2017). In this light, the correlated phenotypic response in this experiment is not entirely unexpected. However, the evolution of multiple multicellular phenotypes in two independent genetic backgrounds was not anticipated. Furthermore, nutrient limiting conditions may have affected PSH in our experiment, but it was not the main driver of the other multicellular phenotypes; rather, it was adherence selection that led to the evolution of hyper-multicellularity.

Previous research on a panel of environmental isolates found no correlation between the phenotypes assayed here (Hope and Dunham, 2014), and in a tractable lab strain capable of aggregative behaviors, each phenotype was associated with its own set of genes (Ryan et al., 2012). However, there is overlap in the requirement of FLO11 and its regulators. Despite the phenotypes being induced by different nutrient signals, there are numerous conserved signaling pathways contributing to filamentous, multicellular growth of all forms (e.g. cAMP-PKA, TOR, filamentous MAPK, Rim101) (Cullen and Sprague, 2012; Granek et al., 2011). It is well known that genetic background and genetic architecture can have strong effects on the expression and correlation of traits (Gasch et al., 2016). In the case of the filamentous phenotypes assayed here, a genetic background that contains variants in the main signaling pathways may lead to a correlation of the phenotypes, while variants expressed later in the development of the phenotype, that are specific to a single trait, may not lead to such a correlation. The effect of the different types of genetic variants suggests that some strains and genetic backgrounds are more likely to evolve virulence from selection in the open environment.

The strains used in this experiment each contain ~50,000 heterozygous sites and differ from each other by ~25,000 SNPs. It is possible that they contained genetic variation in canonical signaling pathways, allowing for the evolution of hyper-multicellular strains. Interestingly, in both backgrounds, pseudohyphal growth appeared to evolve independently of the other phenotypes. Future research will investigate the sorting of the genetic variation, as well as the new mutations, that led to the observed phenotypic evolution in these populations.

Understanding the processes that lead to the emergence of opportunistic fungal pathogens is of increasing importance. In 2022, the World Health Organization issued its first-ever report prioritizing 19 fungal pathogens for research and public health awareness (World Health Organization, 2022); of these, 11 are known to live in the environment (i.e. soil, wood, etc.), including three in the highest priority group (Cryptococcus neoformans, Candida auris, Aspergillus fumigatus). In our experiment, it is unclear which trait was associated with increased virulence: plastic adherence, a different multicellular trait, or general hyper-multicellularity. Regardless of the specific trait causing increased virulence, the experiment demonstrated that selection for a dual-use trait in an environment that is entirely devoid of host organisms can still inadvertently lead to virulence and pathogenicity. The experiment also demonstrated the role that sex can have in increasing rates of adaptation in fungi.

Whether or not increased virulence caused by adherence selection is a general result in fungal microbes remains to be seen. In bacteria, the results are mixed. In Burkholderia cenocepacia, plastic bead selection led to an increase in biofilm phenotypes and mutations previously associated with chronic infections (Poltak and Cooper, 2011; Traverse et al., 2013). Yet, bead selection in P. aeruginosa led to a decrease in biofilm-related phenotypes. It also led to an increase in antibiotic resistance, thus mimicking changes seen in chronic infections (Azimi et al., 2020).

As humans continue to generate novel ecological niches at an unprecedented rate by encroaching on more habitats, using plastics unreservedly (Iroegbu et al., 2021), and especially, as the global climate changes (IPCC Core Writing Team, 2023), the potential for unintended selection grows (Casadevall, 2020). Clinically relevant strains of Escherichia coli can use microplastics in the environment as a reservoir and can even become more virulent after recovery from the ‘plastisphere’ (Ormsby et al., 2023), and it has been shown that plastics in the environment may harbor other pathogenic taxa (Wu et al., 2020). Warmer water temperatures and climate disruptions have been linked to the incidence of illness caused by the marine bacterium Vibrio vulnificus (Martinez-Urtaza et al., 2010), and an increase in global temperature has been hypothesized to be related to the simultaneous emergence of C. auris infections on multiple continents (Jackson et al., 2019; Megha et al., 2020). More generally, the narrowing of the gap between mammalian body temperatures and the ambient environment may create opportunities for fungi to exploit new host niches (Garcia-Solache and Casadevall, 2010). Thus, as new selective pressures act on populations with existing abundant genetic variation, there is the opportunity to coincidentally select a new generation of accidental pathogens.

All data generated or analysed during this study are included in the manuscript and supporting file. Source data files have been provided for Figures 1, 2, and 5. Original and evolved strains are available upon request to the corresponding author.

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Author details

1. Luke I Ekdahl

   Department of Biology, College of William and Mary, Williamsburg, United States

   Contribution

   Data curation, Investigation, Methodology, Writing – review and editing, Conducted phenotyping assays; conducted all virulence assays

   Contributed equally with

   Juliana A Salcedo

   Competing interests

   No competing interests declared

2. Juliana A Salcedo

   Department of Biology, College of William and Mary, Williamsburg, United States

   Contribution

   Data curation, Investigation, Methodology, Evolved all the populations and conducted phenotypic assays

   Contributed equally with

   Luke I Ekdahl

   Competing interests

   No competing interests declared

3. Matthew M Dungan

   Department of Biology, College of William and Mary, Williamsburg, United States

   Present address

   School of Medicine, Vanderbilt University, Nashville, United States

   Contribution

   Investigation, Conducted phenotyping assays

   Competing interests

   No competing interests declared

4. Despina V Mason

   Department of Biology, College of William and Mary, Williamsburg, United States

   Contribution

   Methodology, Developed the evolution protocol

   Competing interests

   No competing interests declared

5. Dulguun Myagmarsuren

   Department of Biology, College of William and Mary, Williamsburg, United States

   Contribution

   Investigation, Conducted FLO11 length analysis

   Competing interests

   No competing interests declared

6. Helen A Murphy

   Department of Biology, College of William and Mary, Williamsburg, United States

   Contribution

   Conceptualization, Data curation, Formal analysis, Funding acquisition, Writing - original draft, Project administration, Writing – review and editing

   For correspondence

   hamurphy@wm.edu

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-4363-4543

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