The transcriptional regulator SpxA1 impacts the virulence, morphology, and redox response of Listeria monocytogenes

Abstract

Bacterial pathogens require precise transcriptional regulation to effectively cause disease. Using a complex regulatory strategy, the model intracellular pathogen Listeria monocytogenes grows successfully as a saprophyte and can rapidly initiate an infectious lifecycle upon ingestion by a host. This dissertation presents a comprehensive analysis of the redox responsive transcriptional regulator SpxA1, which is required for both L. monocytogenes virulence and environmental growth. Whole-cell proteomics and transcriptomics provide evidence that SpxA1 regulates peroxidase abundance, heme biosynthesis, and motility. Subsequent experiments reveal that SpxA1 directly regulates genes via a conserved promoter motif and this interaction is necessary for aerobic growth. Our data further suggest that SpxA1-regulated heme biosynthesis and catalase are essential for aerobic growth in rich broth but dispensable for virulence. While investigating the role of SpxA1 in virulence, we discovered that the ∆spxA1 mutant forms elongated cells with inappropriate frequencies and distributions of division septa. However, critical proteins involved in cell wall biosynthesis, cell division, and DNA damage-regulated elongation were unchanged between wt and ∆spxA1, a result that diverges from previously described homologs. Finally, we demonstrated that both elongation and decreased motility impact the phagocytosis of ∆spxA1. Together, these results describe a novel role for the highly conserved SpxA1 regulator in L. monocytogenes.