The PdxR-PdxKU locus involved in vitamin Bsalvage is important for group A streptococcal resistance to neutrophil killing and survival in human blood.

(Group A, GAS) is a Gram-positive bacterium that inflicts both superficial and life-threatening diseases on its human host. Analysis of fitness using a transposon mutant library revealed that genes predicted to be involved in vitamin Bacquisition are associated with fitness in whole human blood. Vitamin Bis essential for all life and is important for many cellular functions. In several streptococcal species, it has been shown that mutants in Bacquisition exhibited reduced virulence phenotypes and were attenuated during infection. In GAS, Bacquisition is believed to be controlled by thelocus, where PdxR is a positive regulator of, which encodes for a B-substrate kinase and permease, respectively. Mutants in the regulator (Δ) and salvage machinery (Δ) both exhibited modest growth defects when grown in oxygenated conditions with limited vitamin Bprecursors. ∆and ∆mutants also exhibited an impaired ability to survive when challenged with whole human or mouse blood. This defect was characterized by reduced survival in the presence of human neutrophil-like HL60s, primary polymorphonuclear leukocytes, and antimicrobial peptide LL-37. Promoter analysis showed that PdxR is an autoregulator and activatedin the absence of B. Interestingly, ∆and ∆mutants were not attenuated in mouse models of infection, suggesting a species-specific impact on virulence. Overall, it appears thatis associated with GAS vitamin Bmetabolism as well as pathogen survival during encounters with the human innate immune system.IMPORTANCEBacterial pathogens such as(Group A, GAS) must be able to obtain needed nutrients in their human host. Vitamin Bor pyridoxal 5' phosphate is essential for all life and is important for many cellular functions. In other streptococcal pathogens, Bacquisition has been shown to be important for their ability to cause disease. Here, we show that loss of the putative vitamin Bsalvage pathway locusaffects GAS pathogenesis when encountering innate immune responses from phagocytic neutrophils and antimicrobial peptides within the host.pdxKU may contribute to oxygen tolerance through B; however, there appear to be other mechanisms for salvaging vitamin B. Overall,is associated with GAS resistance to the human innate immune response and oxygen tolerance and contributes modestly to Bmetabolism.