Francisella tularensis is a Gram-negative intracellular bacterial pathogen and causative agent of tularemia. We previously identified the outer membrane channel protein TolC as contributing to antimicrobial resistance and subversion of host responses by F. tularensis. To advance understanding of TolC function in Francisella and to identify components that might work together with TolC, we took advantage of a transposon mutant library in F. novicida, a model species that causes a tularemia-like disease in mice. Our findings identify TolC and the membrane fusion protein EmrA1 as important for both antimicrobial resistance and suppression of macrophage cell death. This study also revealed differences in cell death pathways triggered by F. novicida versus F. tularensis infection that may relate to differences in virulence.