Human enteric a-defensin 5 promotes shigella infection by enhancing bacterial adhesion and invasion

Xu, Dan and Liao, Chongbing and Zhang, Bing and Tolbert, W. David and He, Wangxiao and Dai, Zhijun and Zhang, Wei and Yuan, Weirong and Pazgier, Marzena and Liu, Jiankang and Yu, Jun and Sansonetti, Philippe J. and Bevins, Charles L. and Shao, Yongping and Lu, Wuyuan (2018) Human enteric a-defensin 5 promotes shigella infection by enhancing bacterial adhesion and invasion. Immunity, 48 (6). pp. 1233-1244. ISSN 1097-4180

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    Abstract

    Shigella is a Gram-negative bacterium that causes bacillary dysentery worldwide. It invades the intestinal epithelium to elicit intense inflammation and tissue damage, yet the underlying mechanisms of its host selectivity and low infectious inoculum remain perplexing. Here, we report that Shigella coopts human a-defensin 5 (HD5), a host defense peptide important for intestinal homeostasis and innate immunity, to enhance its adhesion to and invasion of mucosal tissues. HD5 promoted Shigella infection in vitro in a structure-dependent manner. Shigella, commonly devoid of an effective host-adhesion apparatus, preferentially targeted HD5 to augment its ability to colonize the intestinal epithelium through interactions with multiple bacterial membrane proteins. HD5 exacerbated infectivity and Shigella-induced pathology in a culture of human colorectal tissues and three animal models. Our findings illuminate how Shigella exploits innate immunity by turning HD5 into a virulence factor for infection, unveiling a mechanism of action for this highly proficient human pathogen.