TheYersinia pestisAil Protein Mediates Binding and Yop Delivery to Host Cells Required for Plague Virulence

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Abstract
Although adhesion to host cells is a critical step in the delivery of cytotoxic Yop proteins byYersinia pestis, the mechanism has not been defined. To identify adhesins critical for Yop delivery, we initiated two transposon mutagenesis screens using themarinertransposon. To avoid redundant cell binding activities, we initiated the screen with a strain deleted for two known adhesins, pH 6 antigen and the autotransporter, YapC, as well as the Caf1 capsule, which is known to obscure some adhesins. The mutants that emerged contained insertions within theail(attachment and invasion locus) gene ofY. pestis. A reconstructed mutant with a single deletion in theaillocus (y1324) was severely defective for delivery of Yops to HEp-2 human epithelial cells and significantly defective for delivery of Yops to THP-1 human monocytes. Specifically, the Yop delivery defect was apparent when cell rounding and translocation of an ELK-tagged YopE derivative into host cells were monitored. Although theailmutant showed only a modest decrease in cell binding capacity in vitro, the KIM5 Δailmutant exhibited a >3,000-fold-increased 50% lethal dose in mice. Mice infected with the Δailmutant also had 1,000-fold fewer bacteria in their spleens, livers, and lungs 3 days after infection than did those infected with the parental strain, KIM5. Thus, the Ail protein is critical for bothY. pestistype III secretion in vitro and infection in mice.

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