Defense Date

8-6-2024

Document Type

Thesis - NSU Access Only

Degree Type

Master of Science

Degree Name

Biological Sciences

First Advisor

Robert Smith, Ph.D

Second Advisor

Lubov Nathanson, Ph. D

Third Advisor

Julie Torruellas Garcia, Ph.D

Keywords

polymicrobial infection, antibiotic tolerance, growth rate, metabolism, virulence, Pseudomonas aeruginosa, Staphylococcus aureus

Abstract

Antibiotic resistance poses a critical threat to public health, with drug-resistant infections accounting for millions of deaths annually. Polymicrobial infections involving complex inter-species interactions exacerbate this challenge by enhancing antibiotic tolerance via competitive interactions, metabolic perturbations and growth inhibition. Using various metabolites, growth and metabolism can be altered, effectively modulating antibiotic efficacy. Guided by this knowledge, we quantified ATP and growth rate, investigating the metabolic and growth dynamics of Pseudomonas aeruginosa and Staphylococcus aureus, two major nosocomial pathogens that frequently co-infect patients with cystic fibrosis and severe burn wounds. We report that P. aeruginosa consistently out-paces S. aureus in ATP production, independent of carbon source utilization. Our findings also reveal that P. aeruginosa exhibits increased sensitivity to kanamycin in the presence of S. aureus, while S. aureus shows heightened tolerance, suggesting a bidirectional interaction likely driven by growth rate, metabolism and competitive interactions. Notably, our results demonstrate that growth rate is an accurate predictor of antibiotic susceptibility of P. aeruginosa in these polymicrobial contexts, exhibiting a linear relationship with growth ratio and bactericidal activity of kanamycin. This study underscores the importance of considering interspecies interactions and growth dynamics in antibiotic susceptibility testing. Our insights pave the way for developing targeted therapeutic strategies that exploit these interspecies dynamics to combat antibiotic resistance effectively.

ORCID ID

0009-0002-1800-132X

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