Salmonella is the cause of millions of food- and water-borne infections
worldwide. Systemic infection and gastroenteritis are the main diseases and
often prove fatal to immunocompromised patients.
Key to Salmonella’s pathogenicity is the survival of several components of the
innate immune system encountered during infection. Reactive oxygen and
nitrogen species (ROS and RNS) are an integral part of this antibacterial
defence of the immune system. Exposure to ROS and RNS occurs within
phagocytic immune cells such as macrophages, where such generation of
radicals is used to combat pathogens. NO is a radical belonging to the group of
RNS that damages bacterial DNA and proteins. Detoxification of NO is essential
during infection to allow Salmonella to survive and replicate within
macrophages. Three enzymes are currently known to help Salmonella to
detoxify NO, but their deletion, however, does not eliminate Salmonella’s
survival. Therefore, it is predicted that further mechanisms for NO detoxification
exist.
In this study, the core NO regulon has been identified: Expression of nine genes
is significantly increased during endogenous and exogenous NO exposure of S.
Typhimurium. Their functions range from carbon starvation, cytochrome
oxidation, iron-sulphur repair and NO reduction to putative proteins with
unknown function, some of which contain domains for tellurite resistance. Single
and combination deletion strains have shown that these genes are important to
decrease anaerobic NO sensitivity of S. Typhimurium and for intracellular
survival in murine macrophages. Furthermore, we have shown for the first time
that the core NO regulon also provides protection against tellurite. Tellurite is
toxic and requires detoxification when encountered. Reducing tellurite to yield
the elemental tellurium results in the release of ROS, which then need to be
detoxified further. Deletion strains sensitive to tellurite have also shown
increased sensitivity to NO. Concurrently, tellurite resistance genes also
facilitate the defence against NO
