Role of Metabolism in Antibiotic Resistance

Each year, more and more multi-drug resistant bacterial strains emerge, thus complicating treatment and increasing the average stay in the intensive care unit. As antibiotics are being rendered inefficient, there is a need to look into ways of weakening the internal state of bacterial cells to make them more susceptible to antibiotics. For this, we first need to understand what methods bacteria employ to fight against antibiotics. In this work, we have reviewed how bacteria respond to antibiotics. There is a similarity in response to antibiotic exposure and starvation (stringent stress) which changes the metabolic state. We have delineated what metabolism changes take place and how they are associated with oxidative stress. For example, there is a common change in NADH concentration that is tied to both metabolism and oxidative stress. Finally, we have compared the findings in literature with our research on an antibiotic-resistant RNA polymerase mutant that alters the gene expression profile in the general areas of metabolism and oxidative stress. Based on this thesis, we have suggested a couple of strategies to make antibiotics more efficient; however, as antibiotic-mediated killing is very complex, researchers need to delve deeper to understand and manipulate the full cellular response.