Understanding the Tradeoff Between ATP Metabolism and Growth in E. coli

Researcher Information

Abstract

The inoculum effect (IE) is a phenomenon in which the minimal inhibitory concentration (MIC) of an antibiotic increases with the density of a bacterial population. IE has been observed for nearly all antibiotics, and has been shown to decrease antibiotic efficacy, prolong the recovery period and increase mortality rates. Despite its ubiquity in the clinic, a mechanism to explain IE for bacteria that expresses antibiotic resistant elements, such as β-lactamases, has yet to be identified. Interesting enough, recent work has shown that interactions between growth rate and metabolism, as determined through ATP production, affect IE for bacteria that lack a genetically encoded resistance mechanism. While interactions between growth and metabolism could explain IE for β-lactamase producing bacteria, this has yet to be explored. Therefore, this study was predominantly focused on understanding the relationship between ATP, growth rate and IE produced by bacteria that express β-lactamase. We found that different ratios of carbon and nitrogen sources affected ATP production and growth directly which would also alter the strength of IE. Additionally, our results suggest a unique tipping point determined by ATP and growth rate where the strength of IE grows considerably. Overall, our results may help us develop novel approaches to treating bacterial infections in the clinic with future patients.

Faculty Sponsors

Dr. Robert Smith

Project Type

Event

Location

Alvin Sherman Library

Start Date

4-6-2022 12:00 PM

End Date

4-7-2022 5:00 PM

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Apr 6th, 12:00 PM Apr 7th, 5:00 PM

Understanding the Tradeoff Between ATP Metabolism and Growth in E. coli

Alvin Sherman Library

The inoculum effect (IE) is a phenomenon in which the minimal inhibitory concentration (MIC) of an antibiotic increases with the density of a bacterial population. IE has been observed for nearly all antibiotics, and has been shown to decrease antibiotic efficacy, prolong the recovery period and increase mortality rates. Despite its ubiquity in the clinic, a mechanism to explain IE for bacteria that expresses antibiotic resistant elements, such as β-lactamases, has yet to be identified. Interesting enough, recent work has shown that interactions between growth rate and metabolism, as determined through ATP production, affect IE for bacteria that lack a genetically encoded resistance mechanism. While interactions between growth and metabolism could explain IE for β-lactamase producing bacteria, this has yet to be explored. Therefore, this study was predominantly focused on understanding the relationship between ATP, growth rate and IE produced by bacteria that express β-lactamase. We found that different ratios of carbon and nitrogen sources affected ATP production and growth directly which would also alter the strength of IE. Additionally, our results suggest a unique tipping point determined by ATP and growth rate where the strength of IE grows considerably. Overall, our results may help us develop novel approaches to treating bacterial infections in the clinic with future patients.