A Novel Role for the Klebsiella pneumoniae Sap (Sensitivity to Antimicrobial Peptides) Transporter in Intestinal Cell Interactions, Innate Immune Responses, Liver Abscess, and Virulence
A Novel Role for the Klebsiella pneumoniae Sap (Sensitivity to Antimicrobial Peptides) Transporter in Intestinal Cell Interactions, Innate Immune Responses, Liver Abscess, and Virulence
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DOI：
10.1093/infdis/jiy615
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发表时间：
2019-04-15
影响因子：
6.4
通讯作者：
Wang, Jin-Town
中科院分区：
文献类型：
--
作者：
Hsu, Chun-Ru;Chang, I-Wei;Wang, Jin-Town
肺炎克雷伯菌是一种重要的人类病原体，可引起医院获得性和社区获得性感染。系统K。肺炎杆菌感染可能在胃肠道定植之前发生，但这种细菌与肠上皮相互作用的基础仍不清楚。在这里，我们报告说，K。肺炎球菌Sap（对抗菌肽的敏感性）转运蛋白有助于细菌-宿主细胞相互作用和体内毒力。基因缺失表明sapA是K.肺炎血液分离物与肠上皮、肺上皮、膀胱上皮和肝细胞的结合。sapA突变体缺乏跨肠上皮细胞单层，巨噬细胞相互作用和诱导促炎细胞因子的易位。在小鼠胃肠道感染模型中，sapA显著降低了肝、脾和肠中的细菌负荷，减少了肝脓肿的产生，并降低了死亡率。这些发现为K.肺炎克雷伯氏菌Sap转运蛋白介导的细胞粘附、肠上皮易位、巨噬细胞相互作用、体内定植、肝脓肿形成和小鼠死亡率。本研究的结果阐明了K.肺炎合并胃肠道感染引起全身感染。
Klebsiella pneumoniae is an important human pathogen causing hospital-acquired and community-acquired infections. Systemic K. pneumoniae infections may be preceded by gastrointestinal colonization, but the basis of this bacterium's interaction with the intestinal epithelium remains unclear. Here, we report that the K. pneumoniae Sap (sensitivity to antimicrobial peptides) transporter contributes to bacterial-host cell interactions and in vivo virulence. Gene deletion showed that sapA is required for the adherence of a K. pneumoniae blood isolate to intestinal epithelial, lung epithelial, urinary bladder epithelial, and liver cells. The sapA mutant was deficient for translocation across intestinal epithelial monolayers, macrophage interactions, and induction of proinflammatory cytokines. In a mouse gastrointestinal infection model, sapA yielded significantly decreased bacterial loads in liver, spleen and intestine, reduced liver abscess generation, and decreased mortality. These findings offer new insights into the pathogenic interaction of K. pneumoniae with the host gastrointestinal tract to cause systemic infection.Klebsiella pneumoniae Sap transporter-mediated cell adherence, intestinal epithelial translocation, macrophage interactions, in vivo colonization, liver abscess formation, and mouse mortality. Findings of the current study elucidate the pathogenic interactions of K. pneumoniae with gastrointestinal tract to cause systemic infection.