Genetic Requirements for Klebsiella pneumoniae -Induced Liver Abscess in an Oral Infection Model

Abstract

Klebsiella pneumoniae is the predominant pathogen of primary liver abscess. However, our knowledge regarding the molecular basis of how K. pneumoniae causes primary infection in the liver is limited. We established an oral infection model that recapitulated the characteristics of liver abscess and conducted a genetic screen to identify the K. pneumoniae genes required for the development of liver abscess in mice. Twenty-eight mutants with attenuated growth in liver or spleen samples out of 2,880 signature-tagged mutants that produced the wild-type capsule were identified, and genetic loci which were disrupted in these mutants were identified to encode products with roles in cellular metabolism, adhesion, transportation, gene regulation, and unknown functions. We further evaluated the virulence attenuation of these mutants in independent infection experiments and categorized them accordingly into three classes. In particular, the class I and II mutant strains exhibited significantly reduced virulence in mice, and most of these strains were not detected in extraintestinal tissues at 48 h after oral inoculation. Interestingly, the mutated loci of about one-third of the class I and II mutant strains encode proteins with regulatory functions, and the transcript abundances of many other genes identified in the same screen were markedly changed in these regulatory mutant strains, suggesting a requirement for genetic regulatory networks for translocation of K. pneumoniae across the intestinal barrier. Furthermore, our finding that preimmunization with certain class I mutant strains protected mice against challenge with the wild-type strain implied a potential application for these strains in prophylaxis against K. pneumoniae infections.

Genotypic and Phenotypic Characterization of Some Virulence Genes of Klebsiella Pneumoniae in Hilla City

“…This study results about the percentage of Klebsiella pneumoniae isolation rates were confirmed by the findings obtained by [7] and [8] who illustrated that immunocompromised patients were more frequently colonized by Klebsiella spp., and agreed with the findings obtained by [9] who instituted that Klebsiella spp. were responsible for many nosocomial infections in adults.…”

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

“…Specifically, two screens were performed to identify K. pneumoniae genes critical for survival in the lung, two were performed for genes required for intestinal colonization (with one of these screens also looking at UTIs), and one screen was performed in a liver abscess model (167,(363)(364)(365)(366). The majority of these screens were performed with classical K. pneumoniae strains, although one screen by Tu et al focused on an HV K. pneumoniae strain (366).…”

“…Specifically, two screens were performed to identify K. pneumoniae genes critical for survival in the lung, two were performed for genes required for intestinal colonization (with one of these screens also looking at UTIs), and one screen was performed in a liver abscess model (167,(363)(364)(365)(366). The majority of these screens were performed with classical K. pneumoniae strains, although one screen by Tu et al focused on an HV K. pneumoniae strain (366). Two other studies used genomic comparisons between K. pneumoniae strains, with one study focusing on classical K. pneumoniae and the other focusing on HV K. pneumoniae, to identify genes of interest and then characterized the roles of specific genes in K. pneumoniae in a mouse lung infection model (168,367).…”

Investigation of class 1 integrons in Klebsiella pneumoniae clinical and microbiota isolates belonging to different phylogenetic groups in Recife, State of Pernambuco

“…Klebsiella pneumoniae is a bacillus that is commonly associated with serious nosocomial infections, such as septicemia, pneumonia, urinary tract infections, and meningitis [1][2][3] . This species is classifi ed into three phylogenetic groups, KpI, KpII, and KpIII, based on nucleotide variations in the constitutively expressed genes gyrA, parC, and rpoB 4,5 .…”