Influence of Growth Efficiency, Bacterial Density, and Metabolism on Antibiotic Resistance in Staphylococcus aureus
Abstract
Antibiotic resistance presents a formidable challenge in medicine, with rising mortality rates and escalating hospital expenses attributed to infections caused by antibiotic-resistant bacteria. To address this critical issue, comprehending the mechanisms of bacterial resistance is paramount to the development of innovate drugs and treatment strategies. One such mechanism is the inoculum effect (IE), where the initial bacterial population density determines the minimum concentration of antibiotic required to eliminate the population. While previous work has shown that for gram negative bacteria, the relationship between ATP production and growth rate can account for the IE. However, it remains unclear as to if the same holds true in gram positive bacteria. To address this knowledge gap, we grew the gram positive bacterium Staphylococcus aureus in M9 medium with different metabolites in varying concentrations of casamino acids, allowing us to manipulate both growth and ATP production. Our findings reveal that [ATP]/growth rate can determine the strength of IE, defined as the difference in the minimum inhibitory concentration by high and low density bacterial populations. If the [ATP]/growth rate is sufficiently high, IE is effectively abolished. Overall, this work extends a novel mechanism to explain IE to gram positive bacteria. Accordingly, our research contributes to the identification of a new mechanism influencing antibiotic resistance, paving the way for potential novel treatment approaches in clinical settings.
Faculty Sponsors
Dr. Robert Smith
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-3-2024 12:30 PM
End Date
4-4-2024 1:30 PM
Influence of Growth Efficiency, Bacterial Density, and Metabolism on Antibiotic Resistance in Staphylococcus aureus
Alvin Sherman Library
Antibiotic resistance presents a formidable challenge in medicine, with rising mortality rates and escalating hospital expenses attributed to infections caused by antibiotic-resistant bacteria. To address this critical issue, comprehending the mechanisms of bacterial resistance is paramount to the development of innovate drugs and treatment strategies. One such mechanism is the inoculum effect (IE), where the initial bacterial population density determines the minimum concentration of antibiotic required to eliminate the population. While previous work has shown that for gram negative bacteria, the relationship between ATP production and growth rate can account for the IE. However, it remains unclear as to if the same holds true in gram positive bacteria. To address this knowledge gap, we grew the gram positive bacterium Staphylococcus aureus in M9 medium with different metabolites in varying concentrations of casamino acids, allowing us to manipulate both growth and ATP production. Our findings reveal that [ATP]/growth rate can determine the strength of IE, defined as the difference in the minimum inhibitory concentration by high and low density bacterial populations. If the [ATP]/growth rate is sufficiently high, IE is effectively abolished. Overall, this work extends a novel mechanism to explain IE to gram positive bacteria. Accordingly, our research contributes to the identification of a new mechanism influencing antibiotic resistance, paving the way for potential novel treatment approaches in clinical settings.
