Decreased efficacy of antimicrobial agents in a polymicrobial environment.
Thomas James O'BrienWendy FigueroaMartin WelchPublished in: The ISME journal (2022)
The airways of people with cystic fibrosis (CF) often harbour diverse polymicrobial communities. These airway infections can be impossible to resolve through antibiotic intervention, even though isolates of the individual species present are susceptible to the treatment when tested in vitro. In this work, we investigate how polymicrobial cultures comprised of key CF-associated pathogens respond to challenge with species-specific antimicrobial agents; colistin (targets Pseudomonas aeruginosa), fusidic acid (targets Staphylococcus aureus), and fluconazole (targets Candida albicans). We found that growth in a polymicrobial environment protects the target microorganism (sometimes by several orders of magnitude) from the effect(s) of the antimicrobial agent. This decreased antimicrobial efficacy was found to have both non-heritable (physiological) and heritable (genetic) components. Whole-genome sequencing of the colistin-resistant P. aeruginosa isolates revealed single nucleotide polymorphisms and indels in genes encoding lipopolysaccharide (LPS) biosynthesis and/or pilus biogenesis, indicating that a previously undescribed colistin resistance mechanism was in operation. This was subsequently confirmed through further genetic analyses. Our findings indicate that the polymicrobial nature of the CF airways is likely to have a significant impact on the clinical response to antimicrobial therapy.
Keyphrases
- cystic fibrosis
- pseudomonas aeruginosa
- staphylococcus aureus
- biofilm formation
- candida albicans
- acinetobacter baumannii
- escherichia coli
- gram negative
- multidrug resistant
- drug resistant
- genome wide
- klebsiella pneumoniae
- inflammatory response
- genetic diversity
- randomized controlled trial
- methicillin resistant staphylococcus aureus
- toll like receptor
- copy number
- stem cells
- single cell
- cell therapy
- lps induced
- anti inflammatory