Polar targeting and assembly of the Legionella Dot/Icm type IV secretion system (T4SS) by T6SS-related components

Legionella pneumophila, the causative agent of Legionnaires disease, survives and replicates inside amoebae and macrophages by injecting a large number of protein effectors into the host cells cytoplasm via the Dot/Icm type IVB secretion system (T4BSS). Previously, we showed that the Dot/Icm T4BSS is localized to both poles of the bacterium and that polar secretion is necessary for the proper targeting of the Legionella containing vacuole (LCV). Here we show that polar targeting of the Dot/Icm core-transmembrane subcomplex (DotC, DotD, DotF, DotG and DotH) is mediated by two Dot/Icm proteins, DotU and IcmF, which are able to localize to the poles of L. pneumophila by themselves. Interestingly, DotU and IcmF are homologs of the T6SS components TssL and TssM, which are part of the T6SS membrane complex (MC). We propose that Legionella co-opted these T6SS components to a novel function that mediates subcellular localization and assembly of this T4SS. Finally, in depth examination of the biogenesis pathway revealed that polar targeting and assembly of the Legionella T4BSS apparatus is mediated by an innovative \"outside-inside\" mechanism.