A Redox-Responsive Transcription Factor Is Critical for Pathogenesis and Aerobic Growth of Listeria monocytogenes

Bacterial pathogens have evolved sophisticated mechanisms to sense and adapt to redox stress in nature and within the host. However, deciphering the redox environment encountered by intracellular pathogens in the mammalian cytosol is challenging, and that environment remains poorly understood. In this study, we assessed the contributions of the two redox-responsive, Spx-family transcriptional regulators to the virulence of , a Gram-positive facultative intracellular pathogen. Spx-family proteins are highly conserved in , and the genome contains two paralogues, and Here, we demonstrate that , but not , is required for the oxidative stress response and pathogenesis. SpxA1 function appeared to be conserved with the homologue, and resistance to oxidative stress required the canonical CXXC redox-sensing motif. Remarkably, was essential for aerobic growth, demonstrating that SpxA1 likely regulates a distinct set of genes. Although the Δ mutant did not grow in the presence of oxygen in the laboratory, it was able to replicate in macrophages and colonize the spleens, but not the livers, of infected mice. These data suggest that the redox state of bacteria during infection differs significantly from that of bacteria growing Further, the host cell cytosol may resemble an anaerobic environment, with tissue-specific variations in redox stress and oxygen concentration.