Influence of Growth Efficiency, Bacterial Density, and Metabolism on Antibiotic Resistance Across Different Drug Classes
Abstract
Antibiotic resistance has become a prevailing issue in the health care system due to increased hospital costs and mortality. Moreover, the discovery of new antibiotics has slowed significantly. Thus, there is a dire need to understand the general mechanisms by which bacteria resist antibiotics towards extending the usefulness of existing drugs. Recently, the effect of metabolism on drug efficiency has revealed that when bacterial metabolism is more active, antibiotics become more lethal. Accordingly, we chose to study how the inoculum effect, where the initial density of bacteria determines the minimum inhibitory concentration (MIC) of drug required, is impacted by bacterial metabolism. To address this question, we grew bacteria in medium containing different metabolites in various concentrations of casamino acids. Together this served to alter both growth and metabolic rate, the intersection of which we call growth efficiency. We observed that, as predicted by flux balance analysis, growth efficiency of a given metabolite determined the difference MIC needed to inhibit bacterial growth. If growth efficiency was sufficiently high, the difference in MIC between high- and low-density populations was effectively zero indicating that inoculum effect was abolished. Our work demonstrates that growth efficiency dictates MIC due to inoculum effect across different drug classes. It serves to establish a new mechanism that can account for antibiotic resistance and may lead to novel treatment approaches in the clinic.
Faculty Sponsors
Dr. Allison Lopatkin, Dr. Robert Smith
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-6-2021 12:00 PM
End Date
4-9-2021 12:00 PM
Influence of Growth Efficiency, Bacterial Density, and Metabolism on Antibiotic Resistance Across Different Drug Classes
Alvin Sherman Library
Antibiotic resistance has become a prevailing issue in the health care system due to increased hospital costs and mortality. Moreover, the discovery of new antibiotics has slowed significantly. Thus, there is a dire need to understand the general mechanisms by which bacteria resist antibiotics towards extending the usefulness of existing drugs. Recently, the effect of metabolism on drug efficiency has revealed that when bacterial metabolism is more active, antibiotics become more lethal. Accordingly, we chose to study how the inoculum effect, where the initial density of bacteria determines the minimum inhibitory concentration (MIC) of drug required, is impacted by bacterial metabolism. To address this question, we grew bacteria in medium containing different metabolites in various concentrations of casamino acids. Together this served to alter both growth and metabolic rate, the intersection of which we call growth efficiency. We observed that, as predicted by flux balance analysis, growth efficiency of a given metabolite determined the difference MIC needed to inhibit bacterial growth. If growth efficiency was sufficiently high, the difference in MIC between high- and low-density populations was effectively zero indicating that inoculum effect was abolished. Our work demonstrates that growth efficiency dictates MIC due to inoculum effect across different drug classes. It serves to establish a new mechanism that can account for antibiotic resistance and may lead to novel treatment approaches in the clinic.
