Single cell, super-resolution imaging reveals an acid pH-dependent conformational switch in SsrB regulates SPI-2.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31033442.
- Also identified by DOI 10.7554/eLife.45311 and PMC identifier 6557628.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
After <i>Salmonella</i> 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 <i>Salmonella</i>; modifying acid survival pathways represents a target for inhibiting <i>Salmonella</i>.
Medical subject headings
- Acids
- Bacterial Proteins
- Hydrogen-Ion Concentration
- Membrane Proteins
- Molecular Conformation
- Salmonella typhimurium
- Transcription Factors