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- W2892957370 endingPage "e12958" @default.
- W2892957370 startingPage "e12958" @default.
- W2892957370 abstract "Professional phagocytic cells such as macrophages are a central part of innate immune defence. They ingest microorganisms into membrane-bound compartments (phagosomes), which acidify and eventually fuse with lysosomes, exposing their contents to a microbicidal environment. Gram-positive Rhodococcus equi can cause pneumonia in young foals and in immunocompromised humans. The possession of a virulence plasmid allows them to subvert host defence mechanisms and to multiply in macrophages. Here, we show that the plasmid-encoded and secreted virulence-associated protein A (VapA) participates in exclusion of the proton-pumping vacuolar-ATPase complex from phagosomes and causes membrane permeabilisation, thus contributing to a pH-neutral phagosome lumen. Using fluorescence and electron microscopy, we show that VapA is also transferred from phagosomes to lysosomes where it permeabilises the limiting membranes for small ions such as protons. This permeabilisation process is different from that of known membrane pore formers as revealed by experiments with artificial lipid bilayers. We demonstrate that, at 24 hr of infection, virulent R. equi is contained in a vacuole, which is enriched in lysosome material, yet possesses a pH of 7.2 whereas phagosomes containing a vapA deletion mutant have a pH of 5.8 and those with virulence plasmid-less sister strains have a pH of 5.2. Experimentally neutralising the macrophage endocytic system allows avirulent R. equi to multiply. This observation is mirrored in the fact that virulent and avirulent R. equi multiply well in extracts of purified lysosomes at pH 7.2 but not at pH 5.1. Together these data indicate that the major function of VapA is to generate a pH-neutral and hence growth-promoting intracellular niche. VapA represents a new type of Gram-positive virulence factor by trafficking from one subcellular compartment to another, affecting membrane permeability, excluding proton-pumping ATPase, and consequently disarming host defences." @default.
- W2892957370 created "2018-10-05" @default.
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- W2892957370 date "2018-11-09" @default.
- W2892957370 modified "2023-10-15" @default.
- W2892957370 title "Virulence‐associated protein A from<i>Rhodococcus equi</i>is an intercompartmental pH‐neutralising virulence factor" @default.
- W2892957370 cites W1613566907 @default.
- W2892957370 cites W181746629 @default.
- W2892957370 cites W1827773344 @default.
- W2892957370 cites W1838606285 @default.
- W2892957370 cites W1839870563 @default.
- W2892957370 cites W1868335667 @default.
- W2892957370 cites W1925012892 @default.
- W2892957370 cites W1933350751 @default.
- W2892957370 cites W1975456337 @default.
- W2892957370 cites W1978066089 @default.
- W2892957370 cites W1980036892 @default.
- W2892957370 cites W1987146298 @default.
- W2892957370 cites W1988901585 @default.
- W2892957370 cites W1990956809 @default.
- W2892957370 cites W1994530356 @default.
- W2892957370 cites W2001312439 @default.
- W2892957370 cites W2002715153 @default.
- W2892957370 cites W2003336619 @default.
- W2892957370 cites W2009058674 @default.
- W2892957370 cites W2011866336 @default.
- W2892957370 cites W2015878939 @default.
- W2892957370 cites W2016101323 @default.
- W2892957370 cites W2030884466 @default.
- W2892957370 cites W2036316917 @default.
- W2892957370 cites W2042048314 @default.
- W2892957370 cites W2047216648 @default.
- W2892957370 cites W2049434243 @default.
- W2892957370 cites W2066135800 @default.
- W2892957370 cites W2074960448 @default.
- W2892957370 cites W2080201761 @default.
- W2892957370 cites W2094207537 @default.
- W2892957370 cites W2095610739 @default.
- W2892957370 cites W2095885733 @default.
- W2892957370 cites W2097799342 @default.
- W2892957370 cites W2104757714 @default.
- W2892957370 cites W2111698215 @default.
- W2892957370 cites W2113173229 @default.
- W2892957370 cites W2113751817 @default.
- W2892957370 cites W2115495414 @default.
- W2892957370 cites W2120771856 @default.
- W2892957370 cites W2121254443 @default.
- W2892957370 cites W2121526389 @default.
- W2892957370 cites W2123927310 @default.
- W2892957370 cites W2124049467 @default.
- W2892957370 cites W2124552187 @default.
- W2892957370 cites W2124813675 @default.
- W2892957370 cites W2125006413 @default.
- W2892957370 cites W2127021716 @default.
- W2892957370 cites W2129907243 @default.
- W2892957370 cites W2131141877 @default.
- W2892957370 cites W2138582125 @default.
- W2892957370 cites W2144379375 @default.
- W2892957370 cites W2152042796 @default.
- W2892957370 cites W2155495207 @default.
- W2892957370 cites W2155847201 @default.
- W2892957370 cites W2170149552 @default.
- W2892957370 cites W2187299608 @default.
- W2892957370 cites W2195753589 @default.
- W2892957370 cites W2475089649 @default.
- W2892957370 cites W2512092116 @default.
- W2892957370 cites W2563544267 @default.
- W2892957370 cites W2724832583 @default.
- W2892957370 cites W2728667464 @default.
- W2892957370 cites W2730857798 @default.
- W2892957370 cites W2751398945 @default.
- W2892957370 cites W2756935311 @default.
- W2892957370 cites W2773892411 @default.
- W2892957370 cites W640211618 @default.
- W2892957370 doi "https://doi.org/10.1111/cmi.12958" @default.
- W2892957370 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30251327" @default.
- W2892957370 hasPublicationYear "2018" @default.