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Genetic Determinants of Antibiotic Resistance and their Effect on Fitness as Determined by Growth Rate Assays


Antibiotic resistance is a major public health crisis in the United States and around the world, with at least 23,000 people dying each year in the U.S. from antibiotic resistant infections; it is a major cause of death. Technical advancements to facilitate studies and diagnosis of resistance are an important step for finding solutions to this problem. For this study, we partnered with a local community hospital Mercy Medical Center. Our study focuses on resistant isolates that have been identified as possessing the Extended Spectrum β-Lactamases (ESBLs). We have used a novel and sensitive method for measuring the fitness of these isolates. By using growth rates as a measurement for fitness we have discovered previously unknown relationships between co-expressed resistance genes. We identified that in the presence of ampicillin, isolates that have both CTX-M-15 and TEM-1 genes have a slightly higher mean growth rate than isolates that have the CTX-M-15 gene but not the TEM-1 gene leading us to believe that there may be a synergistic effect between CTX-M15 and TEM-1 for the resistance of ampicillin. Surprisingly we also found that isolates in the presence of cephalosporin showed a decrease in growth rates if they had the TEM-1 resistance gene. This suggests that the presence of TEM-1 has a slightly inhibitory effect on growth in the presence of cephalosporins, which is still not understood at a cellular level. We also found that in the presence of ampicillin-sulbactam (SAM) there was no difference in growth rates for isolates that were TEM-1 (+) with those that are TEM-1 (-). However there was a difference in mean growth rates when comparing CTX-M-15 (+) isolates and CTX-M-15 (-) isolates in the presence of SAM. Indicating that CTX-M-15 is interfering with resistance for SAM when TEM-1 is present. Growth rates are a reliable measure of fitness. They calculate the maximum growth by measuring the optical density of that culture over time. The sensitivity of these assays may lead to novel findings about the nature of antibiotic resistance evolution. Future studies of fitness outcomes using growth rate assays are recommended.

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