Biology subjects

Kuemmerli, R.

Publications and source records attributed to Kuemmerli, R..

3 recordsLinked to original sources

bioRxiv2018

Understanding policing as a mechanism of cheater control in cooperating bacteria

Policing occurs in insect, animal and human societies, where it is used as a conditional strategy to prevent cheating and enforce cooperation. Recently, it has been suggested that policing might even be relevant in enforcing cooperation in much simpler organisms such as bacteria. Here, we used individual-based modelling to develop an evolutionary concept for policing in bacteria, and identify the conditions under which it can be adaptive. We modelled interactions between cooperators, producing a beneficial public good, cheaters exploiting the public good without contributing to it, and public good producing policers that secrete a toxin to selectively target cheaters. We found that toxin-mediated policing is favored when (i) toxins are potent and durable, (ii) cheap to produce, (iii) cell and public good diffusion is intermediate, and (iv) toxins diffuse farther than the public good. Overall, we show that toxin-mediated policing can enforce cooperation, but the parameter space where it is beneficial seems quite narrow. Moreover, we found that policing decays when the genetic linkage between public good and toxin production breaks. This is because policing is itself a public good, offering protection to toxin-resistant mutants that still produce public goods, yet no longer invest in toxins. Our work suggests that very specific environmental conditions are required for genetically fixed policing mechanisms to evolve in bacteria, and offers empirically testable predictions for their evolutionary stability.

evolutionary biology↗

bioRxiv2018

Environmental determinants of pyoverdine production, exploitation and competition in natural Pseudomonas communities

Many bacteria rely on the secretion of siderophores to scavenge iron from the environment. Laboratory studies revealed that abiotic and biotic factors together determine how much siderophores bacteria make, and whether siderophores can be exploited by non-producing cheaters or be deployed by producers to inhibit competitors. Here, we explore whether these insights apply to natural communities, by comparing the production of the siderophore pyoverdine among 930 Pseudomonas strains from 48 soil and pond communities. We found that pH, iron content, carbon concentration, and community diversity determine pyoverdine production levels, and the extent to which strains are either stimulated or inhibited by heterologous (non-self) pyoverdines. While pyoverdine non-producers occurred in both habitats, their prevalence was higher in soils. Environmental and genetic analysis suggest that non-producers can evolve as cheaters, exploiting heterologous pyoverdine, but also due to pyoverdine disuse in environments with increased iron availability. Overall, we found that environmental factors explained between-strain variation in pyoverdine production much better in soils than in ponds, presumably because high strain mixing in ponds prevents local adaption. Our study sheds light on the complexity of natural bacterial communities, and provides first insights into the multivariate nature of siderophore-based iron acquisition and competition among environmental pseudomonads.

microbiology↗

bioRxiv2017

Probing the evolutionary robustness of anti-virulence treatments targeting iron uptake in Pseudomonas aeruginosa

Background and objectivesTreatments that inhibit the expression or functioning of bacterial virulence factors hold great promise to be both effective and exert weaker selection for resistance than conventional antibiotics. However, the evolutionary robustness argument, based on the idea that anti-virulence treatments disarm rather than kill pathogens, is controversial. Here we probe the evolutionary robustness of two repurposed drugs, gallium and flucytosine, targeting the iron-scavenging pyoverdine of the opportunistic human pathogen Pseudomonas aeruginosa.\n\nMethodologyWe subjected replicated cultures of bacteria to two concentrations of each drug for 20 consecutive days in human serum as an ex-vivo infection model. We screened evolved populations and clones for resistance phenotypes, including the restoration of growth and pyoverdine production, and the evolution of iron uptake by-passing mechanisms. We whole-genome sequenced evolved clones to identify the genetic basis of resistance.\n\nResultsWe found that mutants resistant against anti-virulence treatments readily arose, but their selective spreading varied between treatments. Flucytosine resistance quickly spread in all populations due to disruptive mutations in upp, a gene encoding an enzyme required for flucytosine activation. Conversely, resistance against gallium arose only sporadically, and was based on mutations in transcriptional regulators, upregulating pyocyanin production, a redox-active molecule promoting siderophore-independent iron acquisition. The spread of gallium resistance could be hampered because pyocyanin-mediated iron delivery benefits resistant and susceptible cells alike.\n\nConclusions and implicationsOur work highlights that anti-virulence treatments are not evolutionarily robust per se. Instead, evolutionary robustness is a relative measure, with specific treatments occupying different positions on a continuous scale.

microbiology↗