Gut instinct: Salmonella bacteria's molecular tactics to cau...(sufficient to provide this level of cont...),Health

Date:12/17/2008

sufficient to provide this level of control. Salmonella uses an RNA Mg2+ riboswitch to ensure downregulation of Mg2+ transporters without shutting down bacterial resistance to antimicrobial peptides. Likewise, instead of one regulatory switch, two are needed to properly mitigate conditions of resistance to the bacteriocidal peptides, and amino acid starvation. Enter SlyA.

Two to tango

SlyA is a regulatory protein which cleverly integrates itself into the PhoP/PhoQ regulatory system, allowing for multivariable control. Only when both the PhoP/PhoQ and SlyA regulatory systems are activated can the proper activation of genes for intracellular survival be switched on and delicately maintained.

The sequence of events appears as follows: after cellular invasion and formation of the vacuole, PhoP responds to antimicrobial peptides and/or low levels of Mg2+ within the vacuole by switching on, activating Mg2+ transporters and stimulating the production of SlyA. The PhoP/PhoQ system is sufficient to maintain proper Mg2+ levels, but it is SlyA's job to respond to nutrient starvation. Shi believes SlyA does this by sensing the presence of a particular chemical signalppGpp, (guanosine tetraphosphate), indicative of amino acid depletion. If SlyA detects this chemical, it will act in consort with the PhoP/PhoQ system. With both PhoP/PhoQ and SlyA switches thrown, all the necessary regulatory genes are brought into play, as conditions warrant.

Shi emphasizes that the cluster of genes responsible for this sequence of environmental adaptations to adversity in virulent bacteria like Salmonella are arranged in particular chromosomal regions, the so-called horizontally acquired loci, which are absent in helpful gut bacteria like E. coli.

Disabling either PhoP or SlyA renders Salmonella virtually impotent, its virulence severely attenuated. The bacteria lose their survivability within the macrophage environment, suc
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Contact: Joe Caspermeyer joseph.caspermeyer@asu.edu 480-727-0369 Arizona State University Source:Eurekalert

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