Research Article: Adhesins and Host Serum Factors Drive Yop Translocation by Yersinia into Professional Phagocytes during Animal Infection

Date Published: June 20, 2013

Publisher: Public Library of Science

Author(s): Francisco J. Maldonado-Arocho, Carlos Green, Michael L. Fisher, Michelle K. Paczosa, Joan Mecsas, Denise M. Monack.


Yersinia delivers Yops into numerous types of cultured cells, but predominantly into professional phagocytes and B cells during animal infection. The basis for this cellular tropism during animal infection is not understood. This work demonstrates that efficient and specific Yop translocation into phagocytes by Yersinia pseudotuberculosis (Yptb) is a multi-factorial process requiring several adhesins and host complement. When WT Yptb or a multiple adhesin mutant strain, ΔailΔinvΔyadA, colonized tissues to comparable levels, ΔailΔinvΔyadA translocated Yops into significantly fewer cells, demonstrating that these adhesins are critical for translocation into high numbers of cells. However, phagocytes were still selectively targeted for translocation, indicating that other bacterial and/or host factors contribute to this function. Complement depletion showed that complement-restricted infection by ΔailΔinvΔyadA but not WT, indicating that adhesins disarm complement in mice either by prevention of opsonophagocytosis or by suppressing production of pro-inflammatory cytokines. Furthermore, in the absence of the three adhesins and complement, the spectrum of cells targeted for translocation was significantly altered, indicating that Yersinia adhesins and complement direct Yop translocation into neutrophils during animal infection. In summary, these findings demonstrate that in infected tissues, Yersinia uses adhesins both to disarm complement-dependent killing and to efficiently translocate Yops into phagocytes.

Partial Text

Translocation of effectors via a type III secretion system (TTSS) is an essential process used by many gram-negative bacterial pathogens to thwart immune defenses during infection [1]. Upon mammalian infection, the three pathogenic Yersinia spp., Yptb, Y. enterocolitica and Y. pestis deliver 5–6 Yop effectors into cells of the innate immune system [2]–[4]. Most Yops target and disrupt functions of macrophages, neutrophils and dendritic cells [5]–[8]. While Yop delivery is crucial for the virulence of Yersinia spp.[9], the molecular interactions driving Yop translocation into innate immune cells during tissue infection are not understood.

In order to mount a successful infection, Yersinia must counteract a multitude of host immune responses that are enlisted to control an invading pathogen. One essential mechanism Yersinia spp. use to thwart immune responses is to deliver Yop effector proteins into host cells via a TTSS [8]. These Yops quickly disrupt signal transduction pathways that are normally geared to respond to invading threats and thus allow Yersinia to successfully colonize and persist in the host [8], [9]. This work demonstrates that both bacterial adhesins and host factors contribute to the efficiency of translocation and the specificity of immune cell types translocated with Yops. Furthermore, adhesins contribute to resistance of host complement.




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