Type III secretion translocon assemblies that attenuate Yersinia virulence. (21st January 2013)

• Record Type: Journal Article
• Authors: Costa, Tiago R. D.; Amer, Ayad A. A.; Farag, Salah I.; Wolf‐Watz, Hans; Fällman, Maria; Fahlgren, Anna; Edgren, Tomas; Francis, Matthew S.
• Is Part Of: Cellular microbiology. Volume 15:Number 7(2013:Jul.)
• Page Start: 1088
• Page End: 1110
• Publication Date: 2013-01-21
• Subjects: Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.12100
• Languages: English
• ISSNs: 1462-5814

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Type III secretion enables bacteria to intoxicate eukaryotic cells with anti‐host effectors. A class of secreted cargo are the two hydrophobic translocators that form a translocon pore in the host cell plasma membrane through which the translocated effectors may gain cellular entry. In pathogenic <italic>Yersinia</italic>, YopB and YopD shape this translocon pore. Here, four <italic>in cis</italic> <italic>yopD</italic> mutations were constructed to disrupt a predicted α‐helix motif at the C‐terminus. Mutants YopD_I262P and YopD_K267P poorly localized Yop effectors into target eukaryotic cells and failed to resist uptake and killing by immune cells. These defects were due to deficiencies in host‐membrane insertion of the YopD–YopB translocon. Mutants YopD_A263P and YopD_A270P had no measurable <italic>in vitro</italic> translocation defect, even though they formed smaller translocon pores in erythrocyte membranes. Despite this, all four mutants were attenuated in a mouse infection model. Hence, YopD variants have been generated that can spawn translocons capable of targeting effectors <italic>in vitro</italic>, yet were bereft of any lethal effect <italic>in vivo</italic>. Therefore, Yop translocators may possess other <italic>in vivo</italic> functions that extend beyond being a portal for effector delivery into host cells.</p> </abstract>