A Novel Role for the Klebsiella pneumoniae Sap (Sensitivity to Antimicrobial Peptides) Transporter in Intestinal Cell Interactions, Innate Immune Responses, Liver Abscess, and Virulence

Chun-Ru Hsu, I-Wei Chang, Pei-Fang Hsieh, Tzu-Lung Lin, Pei-Yin Liu, Chen-Hsiu Huang, Kun-Tzu Li, Jin-Town Wang

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Abstract

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 ΔsapA mutant was deficient for translocation across intestinal epithelial monolayers, macrophage interactions, and induction of proinflammatory cytokines. In a mouse gastrointestinal infection model, ΔsapA 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.

Original languageEnglish
JournalJournal of Infectious Diseases
DOIs
Publication statusE-pub ahead of print - Nov 23 2018

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