Abstract
The mammalian intestine is a major site of colonization and a starting point of severe infections by Klebsiella pneumoniae. Inflammatory bowel disease (IBD) is an inflammatory disorder of the gut, and host-derived nitrate in IBD confers a luminal growth advantage upon Escherichia coli and Salmonella typhimurium through nitrate respiration in the inflamed gut. However, the impact of nitrate on the growth and pathogenicity of K. pneumoniae 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 K. pneumoniae wild-type (WT), the nitrate reductase gene mutant strains (ΔnarG, ΔnarZ and ΔnarGΔnarZ), and the molybdate uptake gene mutant strain (ΔmodA) in the inflamed intestinal tract. Results showed that the growth, intestinal colonization, and extraintestinal dissemination of K. pneumoniae were increased in the intestines of dextran sulphate sodium (DSS)-treated mice. Nitrate in the inflamed bowel conferred a growth advantage to K. pneumoniae through nitrate respiration. The molybdate transport protein ModA regulated nitrate reductase activity to increase the growth, intestinal colonization, and extraintestinal dissemination of K. pneumoniae. Tungstate will be a promising antibacterial agent to tackle K. pneumoniae infections in IBD patients.