Abstract
Infections caused by strains of Enterobacteria (like Salmonella Typhimurium) are a serious threat due to being easily transmissible as well as highly virulent. Worldwide, various species of Salmonella cause 93 million cases of gastroenteritis and 155,000 deaths. Many isolates of Salmonella sp. have become resistant to antibiotic treatment, and these can often spread the acquired resistance to, broad-spectrum antibiotics to other non-resistant bacteria. The emergence and spread of antibiotic resistance are a public health emergency and is creating a critical need for alternative treatments that target specific bacterial pathogens. A potential source of new therapeutics are commensal bacteria that produce antimicrobial peptides, as they show the potential for target specificity. One type of antimicrobial peptide of interest are the microcins. Commensal E. coli Nissle 1917 produces two class IIb microcins including the focus of my research, Microcin M (MccM). The genetic determinants for MccM production and function are not completely understood. Two major research aims were investigated, first, to determine the importance of the MccM-associated gene mcmM for MccM production and characterize its function. Second, to determine how resistance to MccM arises in Salmonella and to use resistant mutants to investigate the mode of action of MccM. Understanding the genetic basis for MccM production will enable better design of class IIb-based bacteriotherapeutic agents, while knowledge of the emergence of resistance will be of value in optimizing therapeutic strategies. The results of this study suggest that mcmM does negatively impact the production of MccM however the exact mechanism that it is impacting is not complete understood. This research also demonstrated the mode of action that MccM had on Salmonella Ty. McmM most likely targets the sdaC gene (serine transporter) to get into the susceptible cells and was demonstrated via the creation of non-susceptible mutants to MccM.