Rapid and strain-specific resistance evolution of Staphylococcus aureus against inhibitory molecules secreted by Pseudomonas aeruginosa


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Date

2023-10

Publication Type

Journal Article

ETH Bibliography

yes

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Abstract

Pseudomonas aeruginosa and Staphylococcus aureus frequently occur together in polymicrobial infections, and there is evidence that their interactions negatively affect disease outcome in patients. At the molecular level, interactions between the two bacterial species are well-described, with P. aeruginosa usually being the dominant species suppressing S. aureus through a variety of inhibitory molecules. However, in chronic infections the two species interact over prolonged periods of time, and S. aureus might be able to evolve resistance against inhibitory molecules deployed by P. aeruginosa. Here, we used experimental evolution to test this hypothesis by exposing three different S. aureus strains (Cowan I, 6850, and JE2) to the growth-inhibitory supernatant of P. aeruginosa PAO1 over 30 days. Prior to evolution, we found that S. aureus strains were inhibited by secreted compounds regulatorily controlled by the Pseudomonas quinolone signal quorum-sensing system. Following evolution, inhibitory effects were significantly attenuated, and we observed that adaptations were S. aureus strain specific and involved the upregulation of virulence traits such as staphyloxanthin production and the formation of small colony variants. At the genetic level, mutations in membrane transporters (known to be involved in antibacterial uptake) were the most frequent evolutionary targets. Our work indicates that adaptations of S. aureus to P. aeruginosa occurs rapidly and affect both virulence trait expression and membrane transporter functionality. Thus, pathogen evolution could promote species co-existence and complicate treatment options in infections.

Publication status

published

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Journal / series

Volume

14 (5)

Pages / Article No.

Publisher

American Society for Microbiology

Event

Edition / version

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Subject

microbe-microbe interactions; polymicrobial infections; pathogen evolution; competition; resistance evolution; nosocomial pathogen

Organisational unit

02207 - Functional Genomics Center Zurich / Functional Genomics Center Zurich check_circle

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