All stressed out. Salmonella pathogenesis and reactive nitrogen species

Bacterial pathogens must overcome a range of challenges during the process of infecting their host. The ability of a pathogen to sense and respond appropriately to changes in host environment is vital if the pathogen is to succeed. Mammalian defense strategies include the use of barriers like skin and epithelial surfaces, the production of a chemical arsenal, such as stomach acid and reactive oxygen and nitrogen species, and a highly coordinated cellular and humoral immune response. Salmonella serovars are significant human and animal pathogens which have evolved several mechanisms to overcome mammalian host defense. Here we focus on the interplay which occurs between Salmonella and the host during the infection process, with particular emphasis on the complex bacterial response to reactive nitrogen species produced by the host. We discuss recent advances in our understanding of the key mechanisms which confer bacterial resistance to nitrogen species, which in response to nitric oxide include the flavohemoglobin, HmpA, the flavorubredoxin, NorV, and the cytochrome c nitrite reductase, NrfA, whilst in response to nitrate include a repertoire of nitrate reductases. Elucidating the precise role of different aspects of microbial physiology, nitrogen metabolism, and detoxification during infection will provide valuable insight into novel opportunities and potential targets for the development of therapeutic approaches.