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The type-VII ESX-1 secretion apparatus, encoded by the esx-1 genetic locus, is essential for the export of EsxA and EsxB, two major virulence factors of Mycobacterium tuberculosis. ESX-1 also requires the products of the unlinked espACD operon for optimal function and these proteins are considered integral parts of the secretion apparatus. Here we show that the espACD operon is not necessary for the secretion of EspB, another ESX-1 substrate, and this unimpeded secretion of EspB is associated with significant residual virulence. Upon further investigation, we found that purified EspB can facilitate M.tb virulence even in the absence of EsxA and EsxB, and may do so by binding the bioactive phospholipids phosphatidic acid and phosphatidylserine, both of which are potent bioactive molecules with prominent roles in eukaryotic cell signalling. Our findings provide new insights into the impact of the espACD operon on the ESX-1 apparatus and reveal a distinct virulence function for EspB with novel implications in M.tb-host interactions.
Stewart Cole, Claudia Sala, Ming Zhang, Jérémie Piton, Paloma Julia Soler Arnedo
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Stewart Cole, Andrej Benjak, Anthony Vocat, Jérémie Piton, Shi-Yan Caroline Foo, Andréanne Lupien