Loss of Social Behaviours in Populations of Pseudomonas aeruginosa Infecting Lungs of Patients with Cystic Fibrosis

Natalie Jiricny,Roman Popat,Pauline D Scanlan,Stuart A West,Lorenzo A Santorelli,Kevin Foster,Helle Krogh Johansen,Søren Molin,Ashleigh S Griffin,Melanie Ghoul,Stephen P Diggle

doi:10.1371/journal.pone.0083124

Abstract

Pseudomonas aeruginosa, is an opportunistic, bacterial pathogen causing persistent and frequently fatal infections of the lung in patients with cystic fibrosis. Isolates from chronic infections differ from laboratory and environmental strains in a range of traits and this is widely interpreted as the result of adaptation to the lung environment. Typically, chronic strains carry mutations in global regulation factors that could effect reduced expression of social traits, raising the possibility that competitive dynamics between cooperative and selfish, cheating strains could also drive changes in P. aeruginosa infections. We compared the expression of cooperative traits - biofilm formation, secretion of exo-products and quorum sensing (QS) - in P. aeruginosa isolates that were estimated to have spent different lengths of time in the lung based on clinical information. All three exo-products involved in nutrient acquisition were produced in significantly smaller quantities with increased duration of infection, and patterns across four QS signal molecules were consistent with accumulation over time of mutations in lasR, which are known to disrupt the ability of cells to respond to QS signal. Pyocyanin production, and the proportion of cells in biofilm relative to motile, free-living cells in liquid culture, did not change. Overall, our results confirm that the loss of social behaviour is a consistent trend with time spent in the lung and suggest that social dynamics are potentially relevant to understanding the behaviour of P. aeruginosa in lung infections.

Highlights

Research at the interface of microbiology and evolutionary biology has revealed that populations of bacterial cells are complex communities of individuals that communicate, compete and cooperate with one another [1,2]
Secretion of exo-products There was a significant negative correlation between the production of pyoverdin, and stage of infection, with the least productive strains isolated from patients with chronic infections months) (OH test: F (1, 3) = 18.415, P = P = 0.000014, Bonferroni (0.0125) Figure 1, Figure 2)
We examined a range of social traits in P. aeruginosa strains isolated from outside and inside the lungs of cystic fibrosis patients that were estimated to have been infected for different lengths of time

Summary

Introduction

Research at the interface of microbiology and evolutionary biology has revealed that populations of bacterial cells are complex communities of individuals that communicate, compete and cooperate with one another [1,2]. Many basic functions of bacterial cells involve interaction with neighbouring cells through the release of extra-cellular products. Exo-products are often costly to produce, and laboratory experiments show that cells which cheat by avoiding these costs, can outcompete cooperative neighbours, resulting in reduced survival and viability of the population as a whole [3,4,5]. The competitive dynamics of cooperators and cheats have been the subject of detailed study in the lab, but little is known about these dynamics in natural populations. Very little is known about social behaviours during pathogenic infections, despite the fact that many virulence factors involve the release of exo-products and are, potentially subject to exploitation [6,7]

Methods

Results

Conclusion