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

Area of Science:

• Microbiology
• Infectious Diseases
• Biofilm Research

Background:

• Cystic fibrosis (CF) lung infections involve complex polymicrobial communities.
• These communities are often recalcitrant to antibiotic therapy.
• Current in vitro models lack the microbial diversity of the CF airway.

Purpose of the Study:

• To develop and validate a clinically relevant in vitro polymicrobial biofilm model of the CF lung.
• To investigate how interspecies interactions affect microbial response to antibiotics.
• To understand the mechanisms behind antibiotic recalcitrance in polymicrobial CF infections.

Main Methods:

• Integrated computational approaches and clinical data to select key CF lung microbes.
• Constructed and validated a polymicrobial biofilm model using isolates of *Pseudomonas aeruginosa*, *Staphylococcus aureus*, *Streptococcus sanguinis*, and *Prevotella melaninogenica*.
• Challenged monospecies and polymicrobial biofilms with tobramycin to assess antibiotic sensitivity.

Main Results:

• Polymicrobial communities exhibited altered tobramycin sensitivity compared to monospecies biofilms.
• Wild-type *P. aeruginosa* was sensitized to tobramycin in the mixed community.
• A *P. aeruginosa* LasR loss-of-function mutant showed increased tolerance to tobramycin specifically within the polymicrobial community, linked to elevated phenazine production.

Conclusions:

• Interspecies interactions within polymicrobial biofilms significantly modify microbial antibiotic responses.
• A clinically relevant CF lung polymicrobial model is crucial for understanding treatment recalcitrance.
• Phenazine production by *P. aeruginosa* contributes to community-specific tolerance in CF polymicrobial infections.