A novel virulence gene in Klebsiella pneumoniae strains causing primary liver abscess and septic metastatic complications
Journal
The Journal of experimental medicine
Journal Volume
199
Journal Issue
5
Pages
697
Date Issued
2004-03-01
Author(s)
Abstract
Primary Klebsiella pneumoniae liver abscess complicated with metastatic meningitis or endophthalmitis is a globally emerging infectious disease. Its pathogenic mechanism remains unclear. The bacterial virulence factors were explored by comparing clinical isolates. Differences in mucoviscosity were observed between strains that caused primary liver abscess (invasive) and those that did not (noninvasive). Hypermucoviscosity correlated with a high serum resistance and was more prevalent in invasive strains (52/53 vs. 9/52; P < 0.0001). Transposon mutagenesis identified candidate virulence genes. A novel 1.2-kb locus, magA, which encoded a 43-kD outer membrane protein, was significantly more prevalent in invasive strains (52/53 vs. 14/52; P < 0.0001). The wild-type strain produced a mucoviscous exopolysaccharide web, actively proliferated in nonimmune human serum, resisted phagocytosis, and caused liver microabscess and meningitis in mice. However, magA- mutants lost the exopolysaccharide web and became extremely serum sensitive, phagocytosis susceptible, and avirulent to mice. Virulence was restored by complementation using a magA-containing plasmid. We conclude that magA fits molecular Koch's postulates as a virulence gene. Thus, this locus can be used as a marker for the rapid diagnosis and for tracing the source of this emerging infectious disease.
Subjects
pathogenesis; serum resistance; virulence; genes; liver abscess; meningitis; endophthalmitis
SDGs
Other Subjects
bacterium lipopolysaccharide; complement component C3; DNA; exopolysaccharide; outer membrane protein; protein magA; unclassified drug; virulence factor; animal experiment; animal model; article; bacterial gene; bacterial meningitis; bacterial strain; bacterial virulence; controlled study; DNA sequence; endophthalmitis; female; gene locus; inverse polymerase chain reaction; Klebsiella pneumoniae; liver abscess; magA gene; mouse; nonhuman; phagocytosis; plasmid; priority journal; sepsis; transposon; viscosity; Animals; Base Sequence; DNA, Bacterial; Endophthalmitis; Female; Genes, Bacterial; Genetic Complementation Test; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess; Meningitis, Bacterial; Mice; Mice, Inbred BALB C; Mutation; Sepsis; Virulence; Viscosity
Publisher
ROCKEFELLER UNIV PRESS
Type
journal article
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