Regulation of host tissue responses by pathogen-derived nitric oxide (NO)

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Bacterial pathogens have evolved numerous strategies to colonize multicellular organisms and to counteract or circumvent defense mechanisms of their hosts. Currently, proteins such as toxins, adhesins, iron chelators or immunomodulators are the best understood effectors, which are employed by microbes to target particular processes in their host.We have previously investigated a group of specific bacterial adhesins, which mediate tight attachment of several human-associated microorganism to the surface of the mucosa. Upon host cell binding, these pathogens suppress the exfoliation of superficial epithelial cells, thereby promoting the colonization of the mucosal surface by these microbes. We have now obtained preliminary evidence that the bacterial adhesins constitute a pre-requisite for the intimate attachment, but that it is a gas released by the pathogens (NO; nitric oxid), which ultimately triggers the observed host cell responses. This proposal is set to clarify, if NO release by microorganisms is indeed the critical determinant modulating exfoliation and mucosal colonization. Such a molecular cross-talk by NO would represent a novel mode of communication between prokaryotes and their host. Moreover, as NO-induced processes are amenable to pharmacological intervention, the results of our investigation could open up completely novel avenues to prevent or block infectious diseases.