The<i>Yersinia pestis</i>Ail Protein Mediates Binding and Yop Delivery to Host Cells Required for Plague Virulence
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- Suleyman Felek
- Department of Biologic and Materials Sciences, University of Michigan School of Dentistry
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- Eric S. Krukonis
- Department of Biologic and Materials Sciences, University of Michigan School of Dentistry
Abstract
<jats:title>ABSTRACT</jats:title><jats:p>Although adhesion to host cells is a critical step in the delivery of cytotoxic Yop proteins by<jats:italic>Yersinia pestis</jats:italic>, the mechanism has not been defined. To identify adhesins critical for Yop delivery, we initiated two transposon mutagenesis screens using the<jats:italic>mariner</jats:italic>transposon. 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 the<jats:italic>ail</jats:italic>(attachment and invasion locus) gene of<jats:italic>Y. pestis</jats:italic>. A reconstructed mutant with a single deletion in the<jats:italic>ail</jats:italic>locus (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 the<jats:italic>ail</jats:italic>mutant showed only a modest decrease in cell binding capacity in vitro, the KIM5 Δ<jats:italic>ail</jats:italic>mutant exhibited a >3,000-fold-increased 50% lethal dose in mice. Mice infected with the Δ<jats:italic>ail</jats:italic>mutant 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 both<jats:italic>Y. pestis</jats:italic>type III secretion in vitro and infection in mice.</jats:p>
Journal
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- Infection and Immunity
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Infection and Immunity 77 (2), 825-836, 2009-02
American Society for Microbiology
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Details 詳細情報について
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- CRID
- 1364233270685375104
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- ISSN
- 10985522
- 00199567
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- Data Source
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- Crossref