Genotypic and phenotypic diversity ofStaphylococcus aureusfrom cystic fibrosis lung infections and their interactions withPseudomonas aeruginosa
Authors: Bernardy Eryn E. , Petit Robert A. , Raghuram Vishnu , Alexander Ashley M. , Read Timothy D. , Goldberg Joanna B. 
Published: October 2019

Pseudomonas aeruginosaandStaphylococcus aureusare the most common bacteria that infect the respiratory tract of individuals with the genetic disease cystic fibrosis (CF); in fact,S. aureushas recently overtakenP. aeruginosato become the most common. Substantial research has been performed on the epidemiology ofS. aureusin CF; however, there appears to be a gap in knowledge in regard to the pathogenesis ofS. aureusin the context of CF lung infections. Most studies have focused on a fewS. aureusisolates, often exclusively laboratory adapted strains, and how they are killed byP. aeruginosa. Because of this, little is known about the diversity ofS. aureusCF lung isolates in both virulence and interaction withP. aeruginosa. To begin to address this gap in knowledge, we recently sequenced 65 clinicalS. aureusisolates from the Emory CF Biospecimen Registry and Boston Children’s Hospital, including the reference isolate JE2, a USA300 strain. Here, we analyzed antibiotic resistance genotypes, sequence type, clonal complex,spatype, andagrtype of these isolates. We hypothesized that major virulence phenotypes ofS. aureusthat may be associated with CF lung infections, namely toxin production and mucoid phenotype, would be retained in these isolates. To test our hypothesis, we plated on specific agars and found that most isolates can hemolyze both rabbit and sheep blood (67.7%) and produce polysaccharide (69.2%), consistent with virulence retention in CF lung isolates. We also identified three distinct phenotypic groups ofS. aureusbased on their survival in the presence of nonmucoidP. aeruginosalaboratory strain PAO1 and its mucoid derivative. Altogether, our work provides greater insight into the diversity ofS. aureusCF isolates, specifically the distribution of important virulence factors and their interaction withP. aeruginosa, all of which have implications in patient health.

Author Summary

Staphylococcus aureusis now the most frequently detected pathogen in the lungs of individuals who have cystic fibrosis (CF), followed closely byPseudomonas aeruginosa. When these two pathogens are found to coinfect the CF lung, patients have a significantly worse prognosis. WhileP. aeruginosahas been rigorously studied in the context of bacterial pathogenesis in CF, less is known aboutS. aureus. Here we present an in-depth study of 64S. aureusCF clinical isolates where we investigated genetic diversity utilizing whole genome sequencing, virulence phenotypes, and interactions withP. aeruginosa. We have found thatS. aureusisolated from the CF lung are phylogenetically diverse, most retain known virulence factors, and they vary in interactions withP. aeruginosafrom highly sensitive to completely tolerant. Deepening our understanding of howS. aureusresponds to its environment and other microbes in the CF lung will enable future development of effective treatments and preventative measures against these formidable infections.