Chapter 26 : Epigenetic Phosphorylation Control of Infection and Persistence

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Protein phosphorylation is known to occur across all three kingdoms of life; however, the study of posttranslational modification in bacteria was neglected for a considerable amount of time. Early attempts to detect its presence were unsuccessful, generating the dogma that protein phosphorylation was a regulatory mechanism that emerged late in evolution to meet the needs of organisms composed of multiple and differentiated cells. The pioneering work of several groups in the 1970s identified protein kinase activity in both and ( ), which soon led to the discovery of the histidine/aspartate kinases of the two-component systems ( ). The first aspect of this system involves the stimulation of a histidine kinase by a particular environmental or intracellular signal resulting in autophosphorylation on a key histidine residue. The phospho-histidine can then be used as a substrate by the cognate response regulator for its own autophosphorylation on an aspartate residue. The majority of response regulators are DNA binding proteins that trigger expression from target promoters. Unlike the cross-reactivity observed with serine/threonine/tyrosine (Ser/Thr/Tyr) kinases in eukaryotic cell signaling cascades, two-component systems work in isolation, where a given pairing of histidine kinase and response regulator is highly selective for each other via protein-protein interaction.

Citation: Richard-Greenblatt M, Av-Gay Y. 2017. Epigenetic Phosphorylation Control of Infection and Persistence, p 557-580. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0005-2015
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Figure 1

Hierarchy of STPK activation in response to extracellular and intracellular signals. Master STPKs (blue) sense environmental signals and further cross-phosphorylate the kinase domains of signal transducing (purple) and substrate (red) STPKs to propagate signals and regulate specific downstream proteins. (Figure modified from reference ).

Citation: Richard-Greenblatt M, Av-Gay Y. 2017. Epigenetic Phosphorylation Control of Infection and Persistence, p 557-580. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0005-2015
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Figure 2

STPK cell signaling network associated with persistence. STPKs sense specific environmental cues (starvation, hypoxia, and nitric oxide) and coordinate a physiological response that triggers to enter a state of nonreplicating persistence.

Citation: Richard-Greenblatt M, Av-Gay Y. 2017. Epigenetic Phosphorylation Control of Infection and Persistence, p 557-580. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0005-2015
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