Horizontal gene transfer: Learning from losers
Bacteria can overcome environmental challenges by killing nearby bacteria and incorporating their DNA.
- US Army, United States
The ruthless nature of Darwinian selection does not allow much room for carelessness. So, when a competitor eventually suffers a setback, the obvious response is to leave him in the dust and to snap relentlessly at the heels of anyone further ahead. Now, in eLife, Robert Cooper, Lev Tsimring and Jeff Hasty from the University of California, San Diego report how this may not always be the case (Cooper et al., 2017).
Some organisms, in particular bacteria, have the ability to transfer genetic material from nearby organisms, rather than just between parent and offspring. For many years it was thought that this process, also known as horizontal gene transfer, happened relatively rarely and mostly by accident. Moreover, it was thought that the recipients used the DNA mostly as a source of energy, though incorporation of foreign DNA could drive long-lasting evolutionary trends (Kurland et al., 2003; Nielsen et al., 2014; MacFadyen et al., 2001). In contrast, horizontal gene transfer is increasingly acknowledged as a routine way organisms acquire beneficial and adaptive genes, such as genes that confer resistance against antibiotics and antiseptics. One bacterium can, in effect, ‘learn’ important traits from other bacteria.
Some bacteria can speed up the process of horizontal gene transfer by killing their neighbors in order to get to their DNA. For example, the bacterium Streptococcus pneumoniae secretes toxins to kill sister cells or closely related bacteria, and then extracts their DNA (Steinmoen et al., 2002; Croucher et al., 2016; Wholey et al., 2016). Other bacteria, including the bacterium that causes cholera, use a contact-dependent killing mechanism known as the ‘type VI secretion system’ that involves delivering toxins directly into their victim (Borgeaud et al., 2015).
Cooper et al. placed two distantly related types of bacteria, Acinetobacter baylyi and Escherichia coli, on a surface containing nutrients over which they could grow. E. coli had been modified to produce a fluorescent protein in order to track its fate/whereabouts. The researchers observed that A. baylyi killed E. coli and extracted their DNA, which caused A. baylyi to become fluorescent. Moreover, mutant A. baylyi that had lost the ability to kill were still able to integrate the DNA released when their wild-type siblings killed E. coli. Cooper et al. showed that the extraction of DNA from E. coli and its integration into A. baylyi happened so often it could be observed in real time. A. baylyi that killed the E. coli and released its DNA increased the rate of gene transfer by several orders of magnitude compared to A. baylyi that had been stripped off the ability to kill. This raises the question: what can a bacterium learn from another bacterium that it has just vanquished?
Certain Acinetobacter bacteria thrive in hospital settings, where they can cause serious infections in compromised patients (Oberauner et al., 2013). These bacteria are also able to rapidly develop clinically-impactful antibiotic resistance (Durante-Mangoni et al., 2015). Cooper et al. showed that by killing nearby bacteria, A. baylyi could also acquire genes that made them resistant to antibiotics within hours. The researchers then tested two factors that could theoretically block horizontal gene transfer: enzymes that degrade DNA and irrelevant DNA. The enzymes reduced transfer rates, but the irrelevant DNA did not. Finally, a mathematical model was used to evaluate the experimental data and to simulate a range of conditions that could affect the gene transfer. The simulations showed that killing-enhanced gene transfer was more effective when A. baylyi outnumbered E. coli.
The work of Cooper et al. suggests that horizontal gene transfer rates, and as a particular case, the rate of antibiotic resistance aquisition, could be many orders of magnitude higher than previously thought, therefore challenging current antibiotic-resistance prevention strategies. Moreover, incorporating new genes and thus new abilities into a functioning genome is risky – even more so when the source genome has failed to survive. This risk is, however, minimized if the first bacterium ‘knows’ why the second one has died (that is, it has been killed by the first bacterium) and can, therefore, dismiss the cause of death as irrelevant.
Even under stressful conditions, such as exposure to antibiotics, A. baylyi will still encounter organisms that are able to grow. It will kill them, sample their genomes and may even locate those parts of the genome that enabled the other bacteria to survive (Sandegren and Andersson, 2009). However, it remains unclear to what extent A. baylyi samples the genome of the cells it has killed, and how it regulates the learning process to make it relatively ‘safe’ for themselves.
Bacteria face many selective pressures at any given moment, and most insights obtained through studying interactions between two species will not apply when several species are present (Østman and Adami, 2014; Guimarães et al., 2017). To understand why and how the bacteria learn as they do, we will need to explore DNA exchange under more realistic and multi-dimensional conditions. However, for the moment, Cooper et al. have furthered our understanding in exciting ways.
References
-
Emergence of colistin resistance without loss of fitness and virulence after prolonged colistin administration in a patient with extensively drug-resistant Acinetobacter baumanniiDiagnostic Microbiology and Infectious Disease 82:222–226.https://doi.org/10.1016/j.diagmicrobio.2015.03.013
-
Detecting rare gene transfer events in bacterial populationsFrontiers in Microbiology 4:415.https://doi.org/10.3389/fmicb.2013.00415
-
Recent Advances in the Theory and Application of Fitness Landscapes509–526, Predicting evolution and visualizing high-dimensional fitness landscapes, Recent Advances in the Theory and Application of Fitness Landscapes, Berlin, Heidelberg, Springer.
-
Bacterial gene amplification: implications for the evolution of antibiotic resistanceNature Reviews Microbiology 7:578–588.https://doi.org/10.1038/nrmicro2174
Article and author information
Author details
Publication history
Copyright
© 2017, Kirkup
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,467
- views
-
- 220
- downloads
-
- 1
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Horizontal gene transfer: Learning from losers
eLife 6:e32703.
https://doi.org/10.7554/eLife.32703
Further reading
-
- Biochemistry and Chemical Biology
- Computational and Systems Biology
The spike protein is essential to the SARS-CoV-2 virus life cycle, facilitating virus entry and mediating viral-host membrane fusion. The spike contains a fatty acid (FA) binding site between every two neighbouring receptor-binding domains. This site is coupled to key regions in the protein, but the impact of glycans on these allosteric effects has not been investigated. Using dynamical nonequilibrium molecular dynamics (D-NEMD) simulations, we explore the allosteric effects of the FA site in the fully glycosylated spike of the SARS-CoV-2 ancestral variant. Our results identify the allosteric networks connecting the FA site to functionally important regions in the protein, including the receptor-binding motif, an antigenic supersite in the N-terminal domain, the fusion peptide region, and another allosteric site known to bind heme and biliverdin. The networks identified here highlight the complexity of the allosteric modulation in this protein and reveal a striking and unexpected link between different allosteric sites. Comparison of the FA site connections from D-NEMD in the glycosylated and non-glycosylated spike revealed that glycans do not qualitatively change the internal allosteric pathways but can facilitate the transmission of the structural changes within and between subunits.
-
- Computational and Systems Biology
In eukaryotes, protein kinase signaling is regulated by a diverse array of post-translational modifications, including phosphorylation of Ser/Thr residues and oxidation of cysteine (Cys) residues. While regulation by activation segment phosphorylation of Ser/Thr residues is well understood, relatively little is known about how oxidation of cysteine residues modulate catalysis. In this study, we investigate redox regulation of the AMPK-related brain-selective kinases (BRSK) 1 and 2, and detail how broad catalytic activity is directly regulated through reversible oxidation and reduction of evolutionarily conserved Cys residues within the catalytic domain. We show that redox-dependent control of BRSKs is a dynamic and multilayered process involving oxidative modifications of several Cys residues, including the formation of intramolecular disulfide bonds involving a pair of Cys residues near the catalytic HRD motif and a highly conserved T-loop Cys with a BRSK-specific Cys within an unusual CPE motif at the end of the activation segment. Consistently, mutation of the CPE-Cys increases catalytic activity in vitro and drives phosphorylation of the BRSK substrate Tau in cells. Molecular modeling and molecular dynamics simulations indicate that oxidation of the CPE-Cys destabilizes a conserved salt bridge network critical for allosteric activation. The occurrence of spatially proximal Cys amino acids in diverse Ser/Thr protein kinase families suggests that disulfide-mediated control of catalytic activity may be a prevalent mechanism for regulation within the broader AMPK family.
