Abstract
Bacterial infections are often composed of cells with distinct phenotypes that can be produced by genetic or epigenetic mechanisms. This phenotypic heterogeneity has proved to be important in many pathogens, because it can alter both pathogenicity and transmission. We studied how and why it can emerge during infection in the bacterium Xenorhabdus nematophila, a pathogen that kills insects and multiplies in the cadaver before being transmitted by the soil nematode vector Steinernema carpocapsae We found that phenotypic variants cluster in three groups, one of which is composed of lrp defective mutants. These mutants, together with variants of another group, have in common that they maintain high survival during late stationary phase. This probably explains why they increase in frequency: variants of X. nematophila with a growth advantage in stationary phase (GASP) are under strong positive selection both in prolonged culture and in late infections. We also found that the within-host advantage of these variants seems to trade off against transmission by nematode vectors: the variants that reach the highest load in insects are those that are the least transmitted.IMPORTANCE Pathogens can evolve inside their host, and the importance of this mutation-fueled process is increasingly recognized. A disease outcome may indeed depend in part on pathogen adaptations that emerge during infection. It is therefore important to document these adaptations and the conditions that drive them. In our study, we took advantage of the possibility to monitor within-host evolution in the insect pathogen X. nematophila We demonstrated that selection occurring in aged infection favors lrp defective mutants, because these metabolic mutants benefit from a growth advantage in stationary phase (GASP). We also demonstrated that these mutants have reduced virulence and impaired transmission, modifying the infection outcome. Beyond the specific case of X. nematophila, we propose that metabolic mutants are to be found in other bacterial pathogens that stay for many generations inside their host.
Highlights
Bacterial infections are often composed of cells with distinct phenotypes that can be produced by genetic or epigenetic mechanisms
Xenorhabdus nematophila secondary variants are characterized by a well-known suite of phenotypic traits to which we added in this work their smaller cell size and the fact that they better survive and reach higher densities than group 1 in prolonged culture
Earlier studies have demonstrated that group 2 variants share many of these traits with lrp defective mutants, and it has been proposed that Lrp was controlling phenotypic variation in X. nematophila [20]
Summary
Bacterial infections are often composed of cells with distinct phenotypes that can be produced by genetic or epigenetic mechanisms. In cases where groups of cells with distinct phenotypes interact to better exploit their host [2], the molecular mechanisms driving bacterial diversity can be considered adaptations, which increase pathogen transmission. To demonstrate this theory, it is necessary to understand both what these mechanisms are and how they impact the success of the infection. While mutation generally occurs throughout the whole genome, there are other mechanisms that impact a restricted set of genes These mechanisms can be epigenetic alterations, where clonal populations of bacteria modify their phenotype by changing their regulatory state [5, 6]. Phase variation is described as the basic mechanism that makes antigenic variation a successful instrument for some pathogens to escape their host immune system [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
