Pyridoxine can inhibit salvage of other B 6 vitamers in Salmonella enterica

ABSTRACT Pyridoxal 5′-phosphate (PLP) is a nutrient required by all life. As an essential cofactor, PLP powers enzymatic reactions in primary and secondary metabolism. Microbes can obtain PLP through either de novo PLP biosynthesis or the salvage of exogenous vitamin B 6 . Vitamin B 6 exists in multiple forms (vitamers) in the natural environment, but the effect of mixed B 6 vitamer supplementation on microbial physiology has not been explored. In this study, the ability of Salmonella enterica to obtain PLP during growth in media containing various ratios of B 6 vitamers is examined. The data show that the B 6 vitamer, pyridoxine (PN), can inhibit the salvage of B 6 vitamers, pyridoxamine and pyridoxal, by S. enterica pdxH mutants. Genetic analyses were performed to determine the mechanism by which PN disrupts pyridoxamine and pyridoxal salvage. Mutants resistant to PN inhibition during the salvage of pyridoxamine were isolated and found to encode variants of B 6 kinase (PdxK) with altered activity toward the B 6 vitamer substrates. Suppressor analysis suggests that PN inhibition is, at least, partially due to competitive inhibition of the pyridoxamine kinase activity of PdxK by PN. Additionally, the data indicate that pyridoxine 5′-phosphate (PNP)-mediated toxicity also contributes to growth inhibition by PN. IMPORTANCE Without successful acquisition and utilization of vitamin B 6 , microbes cannot survive or perform their essential roles in human health and the natural environment. Vitamin B 6 exists in multiple forms (vitamers) in the natural world, but the effect of B 6 vitamer mixtures on microbial growth has not been analyzed. This work shows that the B 6 vitamers are not necessarily interchangeable sources of PLP, and they may have distinct effects on microbial physiology.