Two recent publications have provided a detailed look at the function of a Yersinia virulence factor in type III secretion and host immunomodulation.

LcrV is localized in a distinct structure at the tip of the injectisome needle

Type III secretion in the yersiniae involves a secretory apparatus — the injectisome — and the secreted Yersinia outer proteins, or Yops. The injectisome itself comprises a basal body that is embedded in the bacterial membrane and a protruding 'needle', which contains the Yersinia protein YscF. In addition to YscF, three other Yersinia proteins facilitate type III secretion without being secreted into host cells: YopB and YopD, which form the translocation pore, and LcrV (the V antigen), which until now has had an undefined role in the secretion apparatus. Now, reporting in a recent issue of Science, Catherine Mueller, Petr Broz and colleagues provide evidence that LcrV is localized in a distinct structure at the tip of the injectisome needle.

Analysis of the surface of Yersinia enterocolitica E40 by transmission electron microscopy revealed that the needle tip was capped by a well-defined structure. Careful purification of the needle complex revealed that YscF was not the only structural component and showed that LcrV was also present. Deletion of lcrV resulted in the formation of needles lacking the needle tip complex, and this defect could be complemented by LcrV. Immunoelectron microscopy confirmed that LcrV forms a specific structure at the tip of the Yersinia injectisome needle. In a hypothetical model, the authors propose that LcrV functions as an 'assembly platform' that allows the translocation pore to be formed.

In addition to its role in type III secretion, which has now been clearly delineated, LcrV is also known to be involved in modulating the host immune response. In another recent paper, Andreas Sing, Dagmar Reithmeier-Rost and colleagues present experimental evidence confirming that LcrV is involved in Toll-like receptor 2 (TLR2)-dependent interleukin-10 (IL-10) induction in the Y. enterocolitica O:8 strain. Sequence comparison between LcrV and PcrV, the Pseudomonas aeruginosa homologue, had previously pinpointed the TLR2-activating region to N-terminal residues 31–57. The authors used reverse genetics to construct a mutagenized LcrV derivative selectively defective in TLR2 signalling. Analysis of the effects of this mutant strain in mice that were wild-type, TLR2−/− or IL-10−/− showed that the LcrV-mediated TLR2-dependent induction of IL-10 is important for Yersinia virulence and that a single residue — lysine 42 — is crucial for this effect. The authors add that the N-terminal TLR2-activating domain of LcrV might be more important in the virulence of Y. enterocolitica O:8 strains than in the virulence of Yersinia pestis and Yersinia pseudotuberculosis . The results from both papers are consistent with recent results from Susan Straley's group showing that anti-LcrV antibodies had a protective effect in a mouse model of plague.