CHARACTERIZING PEPTIDOGLYCAN PROTEINS IN FRANCISELLA SPECIES TO IDENTIFY POTENTIAL THERAPEUTIC TARGETS

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Hood College Biology

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Hood College Biomedical and Environmental Science

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Public Domain Mark 1.0

Abstract

Francisella tularensis causes tularemia and is a potential biothreat agent with no licensed vaccine. Peptidoglycan, which makes up the cell wall, is a structure unique to bacteria and ideal target for medical countermeasures. Therefore, I sought to characterize the putative peptidoglycan-modifying enzymes murein lytic transglycosylase (mltA), and DD-carboxypeptidases (dacB1 and dacB2) in the surrogate strains Francisella novicida and the Live Vaccine Strain (LVS), and assess gene expression. LVS maintained relatively stable expression of these genes independent of environment. F. novicida, however, exhibited significant changes. dacB1 and mltA are essential for survival in LVS and therefore could serve as potential targets for inhibitors. LVS, along with virulent Francisella strains, contains a truncated version of dacB2, and complementation efforts showed a slight decrease in fitness, indicating the presence of a pathoadaptive mutation, but this requires further investigation. Altogether, these experiments show peptidoglycan-modifying enzymes continue to be viable targets for therapeutics against tularemia.