A novel role for the klebsiella pneumoniae sap (sensitivity to antimicrobial peptides) transporter in intestinal cell interactions, innate immune responses, liver abscess, and virulence
Journal
Journal of Infectious Diseases
Journal Volume
219
Journal Issue
8
Pages
1294-1306
Date Issued
2019
Author(s)
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.
SDGs
Other Subjects
antiinfective agent; virulence factor; animal experiment; animal model; antibiotic sensitivity; Article; bacterial strain; bacterial virulence; bacterium adherence; cell interaction; confocal microscopy; controlled study; cytokine production; female; human; human cell; in vitro study; in vivo study; innate immunity; Klebsiella pneumoniae; Klebsiella pneumoniae infection; liver abscess; macrophage; mouse; nonhuman; phagocytosis; plasmid; polymerase chain reaction; priority journal; sensitivity analysis; animal; Bagg albino mouse; immunology; innate immunity; intestine; Klebsiella infection; liver abscess; microbiology; pathogenicity; pathology; physiology; Animals; Female; Humans; Immunity, Innate; Intestines; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess; Mice; Mice, Inbred BALB C; Virulence Factors
Publisher
Oxford University Press
Type
journal article