Intraspecific diversity among Staphylococcus aureus isolated from cystic fibrosis patients Open Access

Abstract

Staphylococcus aureus was recently recognized as the most common pathogen found in the airway of patients with cystic fibrosis (CF). Current medical microbiology tests in CF are limited in their ability to predict antimicrobial treatment responses in patients. We hypothesize that this is in part impacted by intrahost genotypic diversity and microbial interactions that are yet to be elucidated. Previous studies have shown that S. aureus isolated from CF lungs are diverse phylogenetically and functionally. Here, we present evidence for within-host heterogeneity in the antibiotic resistance gene profile of S. aureus isolated from CF patients. We then examined the effect of interactions between different S. aureus isolates purified from a single CF patient on their growth dynamic and antibiotic-resistance-related phenotypes. Specifically, we studied interactions between methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) isolates obtained from a single sputum sample of an individual with CF. By fluorescently labeling the respective S. aureus isolates, we assessed bacterial growth in cocultures and the impact of antibiotic exposure on their growth dynamics. We also experimentally evolved cocultures of the MRSA and MSSA isolates in increasing concentrations of antibiotics to assess the rate of resistance evolution. Our data suggest that S. aureus coisolated from the same host shows no evidence of adaptation for coexistence in vitro, but exposure to vancomycin helps to stabilize the coexistence. We also showed that coexistence of these isolates does not contribute to a higher rate of antibiotic resistance evolution, suggesting a trade-off between drug resistance and coexistence. Our results highlight the interplay between intraspecific diversity and antibiotic resistance among S. aureus and have implications on efforts to improve the clinical outcome of these infections in CF patients.

Table of Contents

Introduction……………………………………………………………………………….. 1

Results…………………………………………………………………………………….... 4

Discussion…………………………………………………………………………………. 10

Methods……………………………………………………………………………………. 15

Main Figures and Tables……………………………………………………………….. 19

Supplementary Figures…………………………………………………………………. 27

Works Cited……………………………………………………………………………….. 31

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Microbiology
Keyword	intraspecific diversity coexistence cystic fibrosis Staphylococcus aureus antibiotic resistance
Committee Chair / Thesis Advisor	Goldberg, Joanna, Emory University
Committee Members	Gerardo, Nicole, Emory University Read, Timothy, Emory University Alexander, Ashley, Emory University

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