The molybdate transport protein ModA regulates nitrate reductase activity to increase the intestinal colonization and extraintestinal dissemination of <i>Klebsiella pneumoniae</i> in the inflamed gut

The mammalian intestine is a major site of colonization and a starting point of severe infections by <i>Klebsiella pneumoniae</i>. Inflammatory bowel disease (IBD) is an inflammatory disorder of the gut, and host-derived nitrate in IBD confers a luminal growth advantage upon <i>Escherichia coli</i> and <i>Salmonella typhimurium</i> through nitrate respiration in the inflamed gut. However, the impact of nitrate on the growth and pathogenicity of <i>K. pneumoniae</i> in this microenvironment is poorly understood. In this study, we used oral administration of dextran sodium sulphate to induce IBD in mouse models. We then analysed the colonization levels of <i>K. pneumoniae</i> wild-type (WT), the nitrate reductase gene mutant strains (Δ<i>narG</i>, Δ<i>narZ</i> and Δ<i>narG</i>Δ<i>narZ</i>), and the molybdate uptake gene mutant strain (Δ<i>modA</i>) in the inflamed intestinal tract. Results showed that the growth, intestinal colonization, and extraintestinal dissemination of <i>K. pneumoniae</i> were increased in the intestines of dextran sulphate sodium (DSS)-treated mice. Nitrate in the inflamed bowel conferred a growth advantage to <i>K. pneumoniae</i> through nitrate respiration. The molybdate transport protein ModA regulated nitrate reductase activity to increase the growth, intestinal colonization, and extraintestinal dissemination of <i>K. pneumoniae</i>. Tungstate will be a promising antibacterial agent to tackle <i>K. pneumoniae</i> infections in IBD patients.