The ability of pathogenic bacteria to exploit their hosts depends upon various virulence factors, released in response to the concentration of small autoinducer molecules that are also released by the bacteria [1-5]. In vitro experiments suggest that autoinducer molecules are signals used to coordinate cooperative behaviors and that this process of quorum sensing (QS) can be exploited by individual cells that avoid the cost of either producing or responding to signal [6, 7]. However, whether QS is an exploitable social trait in vivo, and the implications for the evolution of virulence [5, 8-10], remains untested. We show that in mixed infections of the bacterium Pseudomonas aeruginosa, containing quorum-sensing bacteria and mutants that do not respond to signal, virulence in an animal (mouse) model is reduced relative to that of an infection containing no mutants. We show that this is because mutants act as cheats, exploiting the cooperative production of signal and virulence factors by others, and hence increase in frequency. This supports the idea that the invasion of QS mutants in infections of humans [11-13] is due to their social fitness consequences [6, 7, 14] and predicts that increased strain diversity will select for lower virulence.
Hamilton's inclusive fitness theory provides a leading explanation for the problem of cooperation. A general result from inclusive fitness theory is that, except under restrictive conditions, cooperation should not be subject to frequency-dependent selection. However, several recent studies in microbial systems have demonstrated that the relative fitness of cheaters, which do not cooperate, is greater when cheaters are rarer. Here we demonstrate theoretically that such frequency-dependent selection can occur in microbes when there is (1) sufficient population structuring or (2) an association between the level of cooperation and total population growth. We test prediction (2) and its underlying assumption, using the pathogenic bacterium Pseudomonas aeruginosa, by competing strains that produce iron-scavenging siderophore molecules (cooperators) with nonproducers (cheaters) at various ratios, under conditions that minimize population structuring. We found that both the relative fitness of cheaters and the productivity of the mixed culture were significantly negatively related to initial cheater frequency. Furthermore, when the period of population growth was experimentally shortened, the strength of frequency dependence was reduced. More generally, we argue that frequency-dependent selection on cooperative traits may be more common in microbes than in metazoans because strong selection, structuring, and cooperation-dependent growth will be more common in microbial populations.
Bacteria often possess multiple siderophore-based iron uptake systems for scavenging this vital resource from their environment. However, some siderophores seem redundant, because they have limited iron-binding efficiency and are seldom expressed under iron limitation. Here, we investigate the conundrum of why selection does not eliminate this apparent redundancy. We focus on Pseudomonas aeruginosa, a bacterium that can produce two siderophores-the highly efficient but metabolically expensive pyoverdine, and the inefficient but metabolically cheap pyochelin. We found that the bacteria possess molecular mechanisms to phenotypically switch from mainly producing pyoverdine under severe iron limitation to mainly producing pyochelin when iron is only moderately limited. We further show that strains exclusively producing pyochelin grew significantly better than strains exclusively producing pyoverdine under moderate iron limitation, whereas the inverse was seen under severe iron limitation. This suggests that pyochelin is not redundant, but that switching between siderophore strategies might be beneficial to trade off efficiencies versus costs of siderophores. Indeed, simulations parameterized from our data confirmed that strains retaining the capacity to switch between siderophores significantly outcompeted strains defective for one or the other siderophore under fluctuating iron availabilities. Finally, we discuss how siderophore switching can be viewed as a form of collective decision-making, whereby a coordinated shift in behaviour at the group level emerges as a result of positive and negative feedback loops operating among individuals at the local scale.
Although cooperative systems can persist in nature despite the potential for exploitation by noncooperators, it is often observed that small changes in population demography can tip the balance of selective forces for or against cooperation. Here we consider the role of population density in the context of microbial cooperation. First, we account for conflicting results from recent studies by demonstrating theoretically that: (1) for public goods cooperation, higher densities are relatively unfavorable for cooperation; (2) in contrast, for self-restraint-type cooperation, higher densities can be either favorable or unfavorable for cooperation, depending on the details of the system. We then test our predictions concerning public goods cooperation using strains of the pathogenic bacterium Pseudomonas aeruginosa that produce variable levels of a public good-iron-scavenging siderophore molecules. As predicted, we found that the relative fitness of cheats (under-producers) was greatest at higher population densities. Furthermore, as assumed by theory, we show that this occurs because cheats are better able to exploit the cooperative siderophore production of other cells when they are physically closer to them. K E Y W O R D S :Kin selection, population structure, Pseudomonas aeruginosa, public goods, siderophores.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.