Journal Article

Pseudomonas aeruginosa exoproducts determine antibiotic efficacy against Staphylococcus aureus

Maile, Robert, Wolfgang, Matthew C., Kartchner, Laurel B., Conlon, Brian P., Radlinski, Lauren, Lachiewicz, Anne M., Cairns, Bruce A., Gode, Cindy J., Rowe, Sarah E., Vitko, Nicholas P.

2017

Overview

Chronic coinfections of Staphylococcus aureus and Pseudomonas aeruginosa frequently fail to respond to antibiotic treatment, leading to significant patient morbidity and mortality. Currently, the impact of interspecies interaction on S. aureus antibiotic susceptibility remains poorly understood. In this study, we utilize a panel of P. aeruginosa burn wound and cystic fibrosis (CF) lung isolates to demonstrate that P. aeruginosa alters S. aureus susceptibility to bactericidal antibiotics in a variable, strain-dependent manner and further identify 3 independent interactions responsible for antagonizing or potentiating antibiotic activity against S. aureus. We find that P. aeruginosa LasA endopeptidase potentiates lysis of S. aureus by vancomycin, rhamnolipids facilitate proton-motive force-independent tobramycin uptake, and 2-heptyl-4-hydroxyquinoline N-oxide (HQNO) induces multidrug tolerance in S. aureus through respiratory inhibition and reduction of cellular ATP. We find that the production of each of these factors varies between clinical isolates and corresponds to the capacity of each isolate to alter S. aureus antibiotic susceptibility. Furthermore, we demonstrate that vancomycin treatment of a S. aureus mouse burn infection is potentiated by the presence of a LasA-producing P. aeruginosa population. These findings demonstrate that antibiotic susceptibility is complex and dependent not only upon the genotype of the pathogen being targeted, but also on interactions with other microorganisms in the infection environment. Consideration of these interactions will improve the treatment of polymicrobial infections.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Anti-Bacterial Agents - pharmacology / Antibacterial agents / Antibiotics / Bacterial infections / Biofilms / Biology and Life Sciences / Burn infection / Burns - microbiology / Burns - pathology / Cellular manufacture / Clinical isolates / Coinfection / Cystic fibrosis / Dosage and administration / Drug Resistance, Bacterial / Endopeptidases / Funding / Genotypes / Glycolipids - metabolism / Glycolipids - pharmacology / Hydroxyquinoline / Immunology / Lungs / Lysis / Medicine and Health Sciences / Mice / Mice, Inbred C57BL / Microbial Interactions - physiology / Microbial Sensitivity Tests / Microbial Viability - drug effects / Microorganisms / Morbidity / Oxygen Consumption - drug effects / Pathogens / Physiological aspects / Protonmotive force / Pseudomonas aeruginosa / Pseudomonas aeruginosa - metabolism / Pseudomonas Infections - metabolism / Pseudomonas Infections - microbiology / Pseudomonas Infections - pathology / Research and Analysis Methods / Rhamnolipids / Staphylococcal Infections - microbiology / Staphylococcal Infections - pathology / Staphylococcus aureus / Staphylococcus aureus - drug effects / Staphylococcus aureus - growth & development / Staphylococcus aureus infections / Staphylococcus infections / Tobramycin / Vancomycin / Vancomycin - pharmacology / Wound Infection - microbiology / Wound Infection - pathology / Wounds