Yersinia pseudotuberculosis uses Ail and YadA to circumvent neutrophils by directing Yop translocation during lung infection.

Summary A Yersinia pseudotuberculosis (Yptb) murine model of lung infection was previously developed using the serotype III IP2666NdeI strain, which robustly colonized lungs but only sporadically dis- seminated to the spleen and liver. We demonstrate here that a serotype Ib Yptb strain, IP32953, colo- nizes the lungs at higher levels and disseminates more efficiently to the spleen and liver compared with IP2666NdeI. The role of adhesins was investi- gated during IP32953 lung infection by construct- ing isogenic Δail, Δinv, ΔpsaE and ΔyadA mutants. An IP32953ΔailΔyadA mutant initially colonized but failed to persist in the lungs and disseminate to the spleen and liver. Yptb expressing these adhesins selectively bound to and targeted neutrophils for translocation of Yops. This selective targeting was critical for virulence because persistence of the ΔailΔyadA mutant was restored following intrana- sal infection of neutropenic mice. Furthermore, Ail and YadA prevented killing by complement- mediated mechanisms during dissemination to and/or growth in the spleen and liver, but not in the lungs. Combined, these results demonstrate that Ail and YadA are critical, redundant virulence factors during lung infection, because they thwart neutrophils by directing Yop-translocation specifi- cally into these cells.