Elsevier

Infection, Genetics and Evolution

Volume 57, January 2018, Pages 8-25
Infection, Genetics and Evolution

Review
Sex in microbial pathogens

https://doi.org/10.1016/j.meegid.2017.10.024 Get rights and content

Highlights

  • Sexual processes are common among microbial pathogens

  • Microbial pathogens experience stresses during infection that damage their genome

  • Recombination repair, a process central to sex, likely promotes pathogen survival and successful infection

  • Most microbial sexual interactions are between two closely related individuals and thus generate little genetic variation

  • Repair of DNA damage is likely the immediate adaptive value of sex in microbial pathogens

Abstract

We review the sexual processes common in pathogenic microorganisms and assess the primary adaptive benefit of such processes. The pathogenic microorganisms considered include bacteria, microbial eukaryotes, and viruses. The sexual processes include bacterial transformation, eukaryotic meiotic sex and virus multiplicity reactivation. Recent evidence shows that sexual processes are common in microbial pathogens. A major general challenge to pathogen survival and infectivity is the need to overcome the hostile defenses of their target host. These defenses characteristically involve production of stresses, including oxidative stress, that can damage the pathogen's genome. Pathogens appear generally to possess enzyme systems that are central to sex and are also associated with a particular type of genomic repair process, recombinational repair. For some pathogens, it has been directly demonstrated that infectivity and virulence depend on sex. The evidence reviewed here supports the conclusion that the primary benefit of sex in pathogens is the repair of genomic damages that would otherwise be deleterious or lethal. This conclusion is in agreement with similar conclusions derived from non-pathogenic model species of bacteria, microbial eukaryotes and viruses. In several pathogenic species it has been shown that the two partner genomes that engage in sex are most often clonally related or closely related genetically. Thus, in pathogenic species, sexual interactions likely generate little or no genetic variation among progeny. However, infrequent outcrossing can occur in these sexual species and this may have important long term consequences.

Introduction

The pathogenic microorganisms considered in this review are bacteria, unicellular and simple multicellular eukaryotes and viruses. Many species in each of these groups are able to undergo a process by which the genomes from two separate individuals interact within a common cytoplasm to form a recombinant genome that may then be passed on to progeny. These processes, although differing in detail between the groups, can be regarded as different forms of sex. In pathogenic bacteria, sex occurs by natural genetic transformation. In unicellular and simple multicellular pathogenic eukaryotes, sex involves syngamy and meiosis. In pathogenic viruses, sex occurs when two or more viruses infect the same host cell.

Sex has two fundamental characteristics: (1) recombination, meaning the exchange of genetic information between two homologous chromosomes, and (2) the chromosomes participating in recombination are usually from two different individual organisms. The microbial pathogens considered here are capable of asexual reproduction as well as sex, and thus are facultatively sexual. Ordinarily, these organisms undergo sex under stressful conditions. Although the life cycles of multicellular plants and animals usually have a predominant diploid phase, this is not generally the case for microbial pathogens, which often exist in a predominantly haploid state.

The primary adaptive function of sex is a fundamental unresolved problem in biology. The competing theories on the resolution of this problem were reviewed by Birdsell and Wills (2003). One of the principal ideas considered was that sex is primarily an adaptation for DNA repair (e.g. Bernstein et al., 1987, Michod, 1994). In 2008 two of us (REM and HB) participated in a review entitled “The adaptive value of sex in microbial pathogens” (Michod et al., 2008). This 2008 review covered relevant findings up to 2007. Since then, a considerable amount of new information has been published that advances our understanding of this topic. It is now appropriate to integrate the new evidence acquired over the past decade into an updated review.

We present evidence here that, among bacterial pathogens, competence for transformation is common and can provide the adaptive benefit of promoting recombinational repair of DNA damage. As the pathogens are predominately haploid, double-strand damage can be repaired via recombination repair with another homologous chromosome. Providing this homologous chromosome for repair is a primary function of sex in these predominately haploid species. This process can protect the pathogen when it is attacked by a host's defensive system that includes production of DNA damaging reactive oxygen species which cause a significant number of double strand breaks that can only be accurately repaired by recombination. Reactive oxygen species include peroxides such as hydrogen peroxide, as well as free radicals such as superoxide, hydroxyl radical and singlet oxygen. Similarly, in unicellular and simple multicellular eukaryotic pathogens, the sexual process of meiosis appears to provide a survival benefit by repairing the pathogen's genome after attack by a host's DNA damaging defenses. Among viral pathogens, sexual interaction occurs when at least two viruses infect the same cell and their genomes undergo recombination with each other. This is also a process that can repair host induced DNA damage.

Section snippets

Overview

In this section on bacterial pathogens, we review the implications of bacterial sex for bacterial pathogenesis. Sex in bacteria occurs mainly by the process of natural transformation, and numerous new examples of transformation among pathogens have been discovered in the past decade. In addition, some of the pathogens previously known to be competent for transformation have now been studied in some depth with respect to the function of transformation in promoting survival and infectivity in the

Meiotic sex as a likely primordial characteristic of eukaryotes

On the basis of a phylogenetic analysis, Dacks and Roger (1999) proposed that facultative sex likely existed in the common ancestor of all eukaryotes. Since this proposal was made, sex was found to occur in several early diverging pathogenic eukaryotic microbes that were previously considered to be asexual. These findings not only suggested that sex may be common among such pathogens, but also contribute to the current understanding that sex is likely a basic and primordial characteristic of

Viral pathogens

Multiplicity reactivation (MR) is a form of sexual interaction between viruses. MR is the process by which two or more viral genomes, each containing lethal damage, interact within the infected cell to form a viable virus genome. Both DNA and RNA viruses are known to be capable of MR. The virus model that has been most intensively studied with respect to MR is bacteriophage (phage) T4. These studies showed that MR is a recombinational repair process that overcomes genome damage (reviewed in

Recombinational repair is central to sexual processes in bacteria, eukaryotes and viruses

Bacterial transformation, meiosis/syngamy in eukaryotic microbes, and multiplicity reactivation in viruses are the sexual processes of pathogenic microbes. These sexual processes have in common recombination between homologous DNA molecules, usually from different individuals. This process is outlined in Fig. 1 for bacteria, eukaryotes and viruses with emphasis on the common central features.

Sex in bacteria occurs by natural transformation (Fig. 1A), a process in which DNA from a donor cell is

Conclusions

For successful infection, invading pathogens must cope with the defensive systems of their hosts that often involve oxidative stress known to damage DNA. Sex provides a redundant template for the accurate and effective recombinational repair of DNA damage. In most of the sexual processes in microbial pathogens reviewed here, recombination involves homologous chromosomes from closely related individuals and so is not an effective means to generate variation by reducing linkage disequilibrium. We

Competing interests

The authors declare no conflict of interest.

Acknowledgments

We thank Erik Hanschen for his valuable comments on an earlier version of the text, allowing significant improvements to be made. We also thank three anonymous reviewers for their very helpful suggestions.

Funding

We gratefully acknowledge the support of the National Aeronautics and Space Administration (NNX13AH41G) and National Science Foundation (MCB-1412395).

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