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Title: Single cell, super-resolution imaging reveals an acid pH-dependent conformational switch in SsrB regulates SPI-2
Authors: Liew, A.T.F. 
Foo, Y.H. 
Gao, Y. 
Zangoui, P. 
Singh, M.K. 
Gulvady, R. 
Kenney, L.J. 
Issue Date: 2019
Publisher: eLife Sciences Publications Ltd
Citation: Liew, A.T.F., Foo, Y.H., Gao, Y., Zangoui, P., Singh, M.K., Gulvady, R., Kenney, L.J. (2019). Single cell, super-resolution imaging reveals an acid pH-dependent conformational switch in SsrB regulates SPI-2. eLife 8 : e45311. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: After Salmonella is phagocytosed, it resides in an acidic vacuole. Its cytoplasm acidifies to pH 5.6; acidification activates pathogenicity island 2 (SPI-2). SPI-2 encodes a type three secretion system whose effectors modify the vacuole, driving endosomal tubulation. Using super-resolution imaging in single bacterial cells, we show that low pH induces expression of the SPI-2 SsrA/B signaling system. Single particle tracking, atomic force microscopy, and single molecule unzipping assays identified pH-dependent stimulation of DNA binding by SsrB. A so-called phosphomimetic form (D56E) was unable to bind to DNA in live cells. Acid-dependent DNA binding was not intrinsic to regulators, as PhoP and OmpR binding was not pH-sensitive. The low level of SPI-2 injectisomes observed in single cells is not due to fluctuating SsrB levels. This work highlights the surprising role that acid pH plays in virulence and intracellular lifestyles of Salmonella; modifying acid survival pathways represents a target for inhibiting Salmonella. © Liew et al.
Source Title: eLife
ISSN: 2050-084X
DOI: 10.7554/eLife.45311
Rights: Attribution 4.0 International
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