Community composition shapes microbial-specific phenotypes in a cystic fibrosis polymicrobial model system

20Citations
Citations of this article
55Readers
Mendeley users who have this article in their library.
Get full text

Abstract

Interspecies interactions can drive the emergence of unexpected microbial phenotypes that are not observed when studying monocultures. The cystic fibrosis (CF) lung consists of a complex environment where microbes, living as polymicrobial biofilm-like communities, are associated with negative clinical outcomes for persons with CF (pwCF). However, the current lack of in vitro models integrating the microbial diversity observed in the CF airway hampers our understanding of why polymicrobial communities are recalcitrant to therapy in this disease. Here, integrating computational approaches informed by clinical data, we built a mixed community of clinical relevance to the CF lung composed of Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus sanguinis and Prevotella melaninogenica. We developed and validated this model biofilm community with multiple isolates of these four genera. When challenged with tobramycin, a front-line antimicrobial used to treat pwCF, the microorganisms in the polymicrobial community show altered sensitivity to this antibiotic compared to monospecies biofilms. We observed that wild-type P. aeruginosa is sensitized to tobramycin in a mixed community versus monoculture, and this observation holds across a range of community relative abundances. We also report that LasR loss-of-function, a variant frequently detected in the CF airway, drives tolerance of P. aeruginosa to tobramycin specifically in the mixed community. Our data suggest that the molecular basis of this community-specific recalcitrance to tobramycin for the P. aeruginosa LasR mutant is increased production of phenazines. Our work support the importance of studying a clinically-relevant model polymicrobial biofilms to understand community-specific traits relevant to infections.

Cite

CITATION STYLE

APA

Jean-Pierre, F., Hampton, T. H., Schultz, D., Hogan, D. A., Groleau, M. C., Déziel, E., & O’toole, G. A. (2023). Community composition shapes microbial-specific phenotypes in a cystic fibrosis polymicrobial model system. ELife, 12. https://doi.org/10.7554/eLife.81604

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free