Abstract

Identifying genetic factors that contribute to the evolution of adaptive phenotypes in pathogenic bacteria is key to understanding the establishment of infectious diseases. In this study, we performed mutation accumulation experiments to record the frequency of mutations and their effect on fitness in hypermutator strains of the environmental bacterium Pseudomonas aeruginosa in comparison to the host-niche-adapted Salmonella enterica. We demonstrate that P. aeruginosa, but not S. enterica, hypermutators evolve toward higher fitness under planktonic conditions. Adaptation to increased growth performance was accompanied by a reversible perturbing of the local genetic context of membrane and cell wall biosynthesis genes. Furthermore, we observed a fine-tuning of complex regulatory circuits involving multiple di-guanylate modulating enzymes that regulate the transition between fast growing planktonic and sessile biofilm-associated lifestyles. The redundancy and local specificity of the di-guanylate signaling pathways seem to allow a convergent shift toward increased growth performance across niche-adapted clonal P. aeruginosa lineages, which is accompanied by a pronounced heterogeneity of their motility, virulence, and biofilm phenotypes.

Highlights

  • Pseudomonas aeruginosa is an environmental generalist and an opportunistic pathogen capable of infecting a wide variety of hosts ranging from plants to humans [1, 2]

  • To elucidate whether the five evolved P. aeruginosa weak bottleneck (WBN) cell lines adapted to the cultivation conditions of the mutation accumulation (MA) experiment, each WBN cell line was streaked out on LB agar, six colonies per cell line were isolated and their growth behavior in LB was compared with the growth behavior of the starting cultures (Fig. 1)

  • P. aeruginosa WBN cell lines adapted to the conditions of the MA experiment by evolving shorter lag phase, faster growth rates, and increased growth yield

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Summary

Introduction

Pseudomonas aeruginosa is an environmental generalist and an opportunistic pathogen capable of infecting a wide variety of hosts ranging from plants to humans [1, 2]. The genomes of P. aeruginosa strains are large (5–7 Mbp) and encode a variety of regulatory circuits. These provide a remarkable phenotypic plasticity and a high adaptation potential to the opportunistic pathogen. For the successful colonizing of new habitats, P. aeruginosa must maintain this adaptation potential even under constant conditions. As it has been observed for various bacteria and yeasts, constant conditions favor the genetic selection of niche specialists, which have a higher fitness, but show fitness decay in other environments [13]. The trade-offs between higher fitness in one, but lower fitness in other environments result from the accumulation of mutations, which are beneficial or neutral under the selective conditions, but deleterious in other environments [13,14,15,16,17,18]

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