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Analysis of fitness using a transposon mutant library revealed that genes predicted to be involved in vitamin B\n              <jats:sub>6<\/jats:sub>\n              acquisition are associated with fitness in whole human blood. Vitamin B\n              <jats:sub>6<\/jats:sub>\n              is essential for all life and is important for many cellular functions. In several streptococcal species, it has been shown that mutants in B\n              <jats:sub>6<\/jats:sub>\n              acquisition exhibited reduced virulence phenotypes and were attenuated during infection. In GAS, B\n              <jats:sub>6<\/jats:sub>\n              acquisition is believed to be controlled by the\n              <jats:italic>pdxR-pdxKU<\/jats:italic>\n              locus, where PdxR is a positive regulator of\n              <jats:italic>pdxKU<\/jats:italic>\n              , which encodes for a B\n              <jats:sub>6<\/jats:sub>\n              -substrate kinase and permease, respectively. Mutants in the regulator (\u0394\n              <jats:italic>pdxR<\/jats:italic>\n              ) and salvage machinery (\u0394\n              <jats:italic>pdxKU<\/jats:italic>\n              ) both exhibited modest growth defects when grown in oxygenated conditions with limited vitamin B\n              <jats:sub>6<\/jats:sub>\n              precursors. \u2206\n              <jats:italic>pdxR<\/jats:italic>\n              and \u2206\n              <jats:italic>pdxKU<\/jats:italic>\n              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 activated\n              <jats:italic>pdxKU<\/jats:italic>\n              in the absence of B\n              <jats:sub>6<\/jats:sub>\n              . Interestingly, \u2206\n              <jats:italic>pdxR<\/jats:italic>\n              and \u2206\n              <jats:italic>pdxKU<\/jats:italic>\n              mutants were not attenuated in mouse models of infection, suggesting a species-specific impact on virulence. Overall, it appears that\n              <jats:italic>pdxR-pdxKU<\/jats:italic>\n              is associated with GAS vitamin B\n              <jats:sub>6<\/jats:sub>\n              metabolism as well as pathogen survival during encounters with the human innate immune system.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                Bacterial pathogens such as\n                <jats:italic>Streptococcus pyogenes<\/jats:italic>\n                (Group A\n                <jats:italic>Streptococcus<\/jats:italic>\n                , GAS) must be able to obtain needed nutrients in their human host. Vitamin B\n                <jats:sub>6<\/jats:sub>\n                or pyridoxal 5\u2019 phosphate is essential for all life and is important for many cellular functions. In other streptococcal pathogens, B\n                <jats:sub>6<\/jats:sub>\n                acquisition has been shown to be important for their ability to cause disease. Here, we show that loss of the putative vitamin B\n                <jats:sub>6<\/jats:sub>\n                salvage pathway locus\n                <jats:italic>pdxR-pdxKU<\/jats:italic>\n                affects GAS pathogenesis when encountering innate immune responses from phagocytic neutrophils and antimicrobial peptides within the host.\n                <jats:italic>pdxR-<\/jats:italic>\n                pdxKU may contribute to oxygen tolerance through B\n                <jats:sub>6<\/jats:sub>\n                ; however, there appear to be other mechanisms for salvaging vitamin B\n                <jats:sub>6<\/jats:sub>\n                . Overall,\n                <jats:italic>pdxR-pdxKU<\/jats:italic>\n                is associated with GAS resistance to the human innate immune response and oxygen tolerance and contributes modestly to B\n                <jats:sub>6<\/jats:sub>\n                metabolism.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.01609-24","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T14:01:57Z","timestamp":1731420117000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["The PdxR-PdxKU locus involved in vitamin B\n            <sub>6<\/sub>\n            salvage is important for group A streptococcal resistance to neutrophil killing and survival in human blood"],"prefix":"10.1128","volume":"12","author":[{"given":"Sarah E.","family":"Davis","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Molecular 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