Klebsiella pneumoniae peptidoglycan-associated lipoprotein and murein lipoprotein contribute to serum resistance, antiphagocytosis, and proinflammatory cytokine stimulation.

Abstract

BACKGROUND:

Peptidoglycan-associated lipoprotein (Pal), murein lipoprotein (LppA), and outer membrane protein A (OmpA) are dominant outer membrane proteins (OMPs) that are released by gram-negative bacteria during sepsis. OMPs are implicated in the maintenance of cell envelope integrity. Here, we characterize the roles of these OMPs in pathogenesis during bacteremia caused by Klebsiella pneumoniae.

METHODS:

pal-, lppA-, and ompA-deficient K. pneumoniae strains were constructed using an unmarked deletion method. Serum sensitivity, antiphagocytosis activity, outer membrane permeability, and sensitivity to anionic detergents and antimicrobial polypeptides were determined for these OMP gene deletion mutants. The ability of these OMP gene deletion mutants to induce immune responses was compared with that of the wild-type strain in a bacteremic mouse model.

RESULTS:

Klebsiella pneumoniae strains deleted for pal or lppA exhibited reduced protection from serum killing and phagocytosis; perturbation to the outer membrane permeability barrier and hypersensitivity to bile salts and sodium dodecyl sulfate. The strain mutated for lppA had reduced ability to activate Toll-like receptor 4. Immunization of mice with the pal or lppA mutant provided protection against infection by the wild-type strain.

CONCLUSIONS:

Our findings indicate that K. pneumoniae Pal and LppA proteins are important in the maintenance of cell integrity, contribute to virulence, and could be used as attenuated vaccines.

• Authors: Pei-Fang Hsieh, Ju-Yun Liu, Yi-Jiun Pan, Meng-Chuan Wu, Tzu-Lung Lin, Yen-Te Huang, Jin-Town Wang
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 208 Issue 10 Pg. 1580-9 (Nov 15 2013) ISSN: 1537-6613 [Electronic] United States
• PMID: 23911714 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Bacterial Outer Membrane Proteins
• Cytokines
• Detergents
• Inflammation Mediators
• Peptidoglycan

Topics

• Animals
• Anti-Bacterial Agents (pharmacology)
• Bacterial Outer Membrane Proteins (genetics, immunology, metabolism)
• Cell Membrane Permeability
• Cytokines (immunology)
• Detergents (metabolism, pharmacology)
• Disease Models, Animal
• Humans
• Inflammation Mediators (immunology)
• Klebsiella Infections (immunology, prevention & control)
• Klebsiella pneumoniae (drug effects, genetics, immunology)
• Mice
• Microbial Sensitivity Tests
• Mutation
• Neutrophils (immunology, microbiology)
• Peptidoglycan (immunology)
• Phagocytosis (immunology)
• Phenotype
• Virulence (genetics, immunology)