|Abstract||The bacterium Bacillus anthracis, the causative agent for the disease anthrax, possesses two plasmids that contribute significantly to virulence. Besides plasmids, certain chromosomal genes also contribute. In previous studies, our lab discovered that the chromosomally encoded clpX gene is essential for virulence in B. anthracis. ClpX is an ATPase that is part of the ClpXP proteasome found in many bacteria. Loss of ClpX in B. anthracis Sterne results in increased susceptibility to cell wall targeting antibiotics like penicillin and daptomycin. However, the mechanism behind ClpX's role in antibiotic resistance is not well understood and it is likely that multiple pathways are affected by the loss of this global protease. We recently conducted a microarray to find which genes are up or down regulated in Delta-ClpX compared to wild-type (WT) B. anthracis. 119 genes had disrupted regulation and several of these had been connected to cell-wall active antibiotics like penicillin. In this study, we focused on three of these genes: msrA, glpF, and sigM. We confirmed the microarray results and showed that msrA, glpF, and sigM gene expression in our Delta-ClpX strains significantly differs from the wild-type B. anthracis Sterne via QPCR. Insertional knockout mutants were made for glpF and sigM to test whether these genes were necessary for antibiotic resistance. We found removing sigM results in increased susceptibility to penicillin, but no conclusive results could be drawn for daptomycin. We tested the virulence of both mutants in our invertebrate animal model G. mellonella and found notable decreases in virulence for both Delta-SigM and Delta-GlpF. Thus, SigM appears to also mediate antibiotic resistance and may at least partially account for the loss of resistance seen in the Delta-ClpX mutant. Further studies will be needed to confirm the exact role in mediating antimicrobial resistance and potentially virulence for B. anthracis.