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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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

Fingerprint

Liver Abscess
Klebsiella pneumoniae
Innate Immunity
Cell Communication
Virulence
Klebsiella Infections
Community-Acquired Infections
Bacterial Load
Liver
Gene Deletion
Intestinal Mucosa
Infection
Intestines
Gastrointestinal Tract
Urinary Bladder
Spleen
Epithelial Cells
Macrophages
intestinal peptide-proton cotransporter
Cytokines

Cite this

A Novel Role for the Klebsiella pneumoniae Sap (Sensitivity to Antimicrobial Peptides) Transporter in Intestinal Cell Interactions, Innate Immune Responses, Liver Abscess, and Virulence. / Hsu, Chun-Ru; Chang, I-Wei; Hsieh, Pei-Fang; Lin, Tzu-Lung; Liu, Pei-Yin; Huang, Chen-Hsiu; Li, Kun-Tzu; Wang, Jin-Town.

In: Journal of Infectious Diseases, 23.11.2018.

Research output: Contribution to journalArticle

@article{3374eb1b99ef4377b6c42e5d1f259ce9,
title = "A Novel Role for the Klebsiella pneumoniae Sap (Sensitivity to Antimicrobial Peptides) Transporter in Intestinal Cell Interactions, Innate Immune Responses, Liver Abscess, and Virulence",
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.",
keywords = "Klebsiella pneumoniae, Sap transporter, liver abscess, intestinal cell, virulence",
author = "Chun-Ru Hsu and I-Wei Chang and Pei-Fang Hsieh and Tzu-Lung Lin and Pei-Yin Liu and Chen-Hsiu Huang and Kun-Tzu Li and Jin-Town Wang",
year = "2018",
month = "11",
day = "23",
doi = "10.1093/infdis/jiy615",
language = "English",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",

}

TY - JOUR

T1 - A Novel Role for the Klebsiella pneumoniae Sap (Sensitivity to Antimicrobial Peptides) Transporter in Intestinal Cell Interactions, Innate Immune Responses, Liver Abscess, and Virulence

AU - Hsu, Chun-Ru

AU - Chang, I-Wei

AU - Hsieh, Pei-Fang

AU - Lin, Tzu-Lung

AU - Liu, Pei-Yin

AU - Huang, Chen-Hsiu

AU - Li, Kun-Tzu

AU - Wang, Jin-Town

PY - 2018/11/23

Y1 - 2018/11/23

N2 - 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.

AB - 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.

KW - Klebsiella pneumoniae

KW - Sap transporter

KW - liver abscess

KW - intestinal cell

KW - virulence

U2 - 10.1093/infdis/jiy615

DO - 10.1093/infdis/jiy615

M3 - Article

C2 - 30476200

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

ER -