Effect of β-lactamase expression and varying metabolism on the Inoculum Effect
Abstract
Infections with antibiotic resistant bacteria pose a substantial challenge to the field of medicine. Accordingly, it is of the utmost importance that we understand the mechanisms by which bacteria resist antibiotics towards the development of novel drugs and treatment paradigms. One mechanism by which a population of bacteria can resist an antibiotic is the inoculum effect (IE). During IE, the initial density of the population determines the efficacy of the antibiotic; highly dense populations of bacteria require more antibiotics to kill the population as compared to less dense populations. One mechanism that has been proposed to explain IE is the collective degradation of antibiotics. For bacteria that express antibiotic degrading enzymes, such as β-lactamases, a higher density would allow a population to work together to degrade the antibiotic more effectively than a lower density population. However, this likely depends upon the amount of enzyme produced. While producing more enzymes would result in faster collective degradation, it would also reduce growth owing to increased energy devotion to antibiotic degradation. In contrast, while producing less antibiotic degrading enzyme would make the population more susceptible to antibiotics, it would also allow for increased growth, which may allow for increased collective degradation. While plausible, this has yet to be explored. Accordingly, we used β-lactamase expressing Escherichia coli to investigate trade-offs between enzyme production, growth, and IE. We found that changing the rate of β-lactamase production coupled with altering nitrogen source abundance altered the severity of IE, which coincided with changes in growth rate. Moreover, we found that βlactamase production was more important than growth rate; although growth rate increases with less production, reducing β-lactamase production makes the population increasing susceptibility to antibiotics. Our results may have implications in the use of β-lactam antibiotics in the clinic to treat infection of high density.
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
Effect of β-lactamase expression and varying metabolism on the Inoculum Effect
Alvin Sherman Library
Infections with antibiotic resistant bacteria pose a substantial challenge to the field of medicine. Accordingly, it is of the utmost importance that we understand the mechanisms by which bacteria resist antibiotics towards the development of novel drugs and treatment paradigms. One mechanism by which a population of bacteria can resist an antibiotic is the inoculum effect (IE). During IE, the initial density of the population determines the efficacy of the antibiotic; highly dense populations of bacteria require more antibiotics to kill the population as compared to less dense populations. One mechanism that has been proposed to explain IE is the collective degradation of antibiotics. For bacteria that express antibiotic degrading enzymes, such as β-lactamases, a higher density would allow a population to work together to degrade the antibiotic more effectively than a lower density population. However, this likely depends upon the amount of enzyme produced. While producing more enzymes would result in faster collective degradation, it would also reduce growth owing to increased energy devotion to antibiotic degradation. In contrast, while producing less antibiotic degrading enzyme would make the population more susceptible to antibiotics, it would also allow for increased growth, which may allow for increased collective degradation. While plausible, this has yet to be explored. Accordingly, we used β-lactamase expressing Escherichia coli to investigate trade-offs between enzyme production, growth, and IE. We found that changing the rate of β-lactamase production coupled with altering nitrogen source abundance altered the severity of IE, which coincided with changes in growth rate. Moreover, we found that βlactamase production was more important than growth rate; although growth rate increases with less production, reducing β-lactamase production makes the population increasing susceptibility to antibiotics. Our results may have implications in the use of β-lactam antibiotics in the clinic to treat infection of high density.
