Copyright Statement

All rights reserved. This publication is intended for use solely by faculty, students, and staff of Nova Southeastern University. No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, now known or later developed, including but not limited to photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author or the publisher.

Defense Date


Document Type

Thesis - NSU Access Only

Degree Type

Master of Science

Degree Name

Biological Sciences

First Advisor

Robert P. Smith, Ph.D.

Second Advisor

Omar T. Eldakar, Ph.D.

Third Advisor

Julie Torruellas Garcia, Ph.D.


Growth productivity, inoculum effect, metabolism, growth rate, antibiotic tolerance, Pseudomonas aeruginosa


The emergence of antibiotic resistance represents one of the greatest threats to global health in the 21st century. The issue is exacerbated by the slow development of new antibiotics to combat infections. Therefore, it is crucial to understand how bacterial populations can tolerate antibiotic treatment collectively to prevent the rampant evolution of antibiotic-resistant bacteria and develop novel approaches to extend the efficacy of existing antibiotics. One widely observed mechanism is the inoculum effect (IE), where antibiotic lethality decreases as the initial bacterial density increases. Previous research suggests that growth productivity, the relationship between growth and metabolism, can explain IE, but this has yet to be explored in Pseudomonas aeruginosa. Accordingly, we investigated the effect of five carbon sources across a wide range of equimolar amino acid concentrations on the metabolism, growth rate, and IE of P. aeruginosa. Our findings indicate that changes in nutrient availability impact both the growth productivity and IE in this pathogen. Specifically, differences in growth productivity can determine IE; when growth productivity increases, the average strength of IE for the aminoglycoside kanamycin decreases in P. aeruginosa. Thus, under optimal growth conditions, the density-dependent antibiotic tolerance of P. aeruginosa can be reduced. To further explore this relationship, we examined the ratio of log[ATP]/growth rate as a proxy for growth productivity for each carbon source and amino acid concentration combination. Our results suggest that this ratio can also predict IE. Notably, at an intermediate equimolar amino acid concentration of 0.0075 mM, when the ratio of log[ATP]/growth rate was sufficiently high, IE was effectively eliminated. Overall, our study highlights the importance of the growth environment in determining growth productivity and IE in P. aeruginosa. These insights may contribute to the development of novel strategies that reduce IE in the clinic without the need to increase antibiotic dosages to treat high-density P. aeruginosa infections.


This research was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health and was accomplished under Grant Number R15AI159902

Available for download on Thursday, July 27, 2028

To access this thesis/dissertation you must have a valid OR email address and create an account for NSUWorks.

Free My Thesis

If you are the author of this work and would like to grant permission to make it openly accessible to all, please click the Free My Thesis button.

  Contact Author