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Ena/VASP proteins contribute to Listeria monocytogenes pathogenesis by controlling temporal and spatial persistence of bacterial actin‐based motility
Author(s) -
Auerbuch Victoria,
Loureiro Joseph J.,
Gertler Frank B.,
Theriot Julie A.,
Portnoy Daniel A.
Publication year - 2003
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.2003.03639.x
Subject(s) - listeria monocytogenes , biology , actin , microbiology and biotechnology , motility , cytoskeleton , actin cytoskeleton , directionality , cofilin , genetics , cell , bacteria
Summary The Listeria monocytogenes surface protein ActA mediates actin‐based motility by interacting with a number of host cytoskeletal components, including Ena/VASP family proteins, which in turn interact with actin and the actin‐binding protein profilin. We employed a bidirectional genetic approach to study Ena/VASP′s contribution to L. monocytogenes movement and pathogenesis. We generated an ActA allelic series within the defined Ena/VASP‐binding sites and introduced the resulting mutant L. monocytogenes into cell lines expressing different Ena/VASP derivatives. Our findings indicate that Ena/VASP proteins contribute to the persistence of both speed and directionality of L. monocytogenes movement. In the absence of the Ena/VASP proline‐rich central domain, speed consistency decreased by sixfold. In addition, the Ena/VASP F‐actin‐binding region increased directionality of bacterial movement by fourfold. We further show that both regions of Ena/VASP enhanced L. monocytogenes cell‐to‐cell spread to a similar degree, although the Ena/VASP F‐actin‐binding region did so in an ActA‐independent manner. Surprisingly, our ActA allelic series enabled us to uncouple L. monocytogenes speed from directionality although both were controlled by Ena/VASP proteins. Lastly, we showed the pathogenic relevance of these findings by the observation that L. monocytogenes lacking ActA Ena/VASP‐binding sites were up to 400‐fold less virulent during an adaptive immune response.