Genotypes of Klebsiella oxytoca Isolates from Patients with Nosocomial Pneumonia Are Distinct from Those of Isolates from Patients with Antibiotic-Associated Hemorrhagic Colitis

Abstract

Klebsiella oxytoca acts as a pathobiont in the dysbiotic human intestinal microbiota, causing antibiotic-associated hemorrhagic colitis (AAHC), but it also infects other organs, resulting in pneumonia and urinary tract and skin infections. The virulence of K. oxytoca is still poorly understood. The production of a specific cytotoxin has been linked to AAHC pathogenesis. To investigate the clonal relationships of K. oxytoca with regard to clinical origin and virulence attributes, we established a multilocus sequence typing (MLST) method and analyzed 74 clinical K. oxytoca isolates from asymptomatic carriers and patients with AAHC, respiratory infections, and other infections. The isolates were phenotypically characterized, typed, and compared phylogenetically based on the sequences of seven housekeeping genes. MLST analysis yielded 60 sequence types, 12 of which were represented by more than one isolate. The phylogenetic tree distinguished clusters of K. oxytoca isolates between patients with AAHC and those with respiratory infections. Toxin-positive and -negative strains were observed within one sequence type. Our findings indicate that AAHC isolates share a genetic background. Interestingly, K. oxytoca isolates from nosocomial pneumonia showed a different genetic clustering, suggesting that these strains do not originate from the intestines or that they are specialized for respiratory tract colonization. Our results further indicate a polyphyletic origin and possible horizontal transfer of the genes involved in K. oxytoca cytotoxin production. This work provides evidence that K. oxytoca isolates colonizing the two main clinically relevant habitats (lower gastrointestinal [GI] tract and respiratory tract) of the human host are genetically distinct. Applications of this MLST analysis should help clarify the sources of nosocomial infections.

Enterotoxicity of a nonribosomal peptide causes antibiotic-associated colitis

“…Secreted products of K. oxytoca strains isolated from AAHC patients have cytotoxic effects on human epithelial cells in vitro (13,(18)(19)(20)(21). We asked whether the cytotoxic properties of K. oxytoca observed in vitro are important to development of the…”

Contaminated Handwashing Sinks as the Source of a Clonal Outbreak of KPC-2-Producing Klebsiella oxytoca on a Hematology Ward

“…Repetitive sequence-based PCR (rep-PCR) was carried out with the DiversiLab system (bioMérieux, Nürtingen, Germany). In addition, all the isolates were tested using multilocus sequence typing (MLST), as described previously (15).…”

The Toxin-Producing Pathobiont Klebsiella oxytoca Is Not Associated with Flares of Inflammatory Bowel Diseases

“…The strain collection at the Institute of Molecular Biosciences, University of Graz, consists of more than 300 fecal K. oxytoca strains from patients with AAHC, antibiotic-associated diarrhea and IBD, healthy carriers but also includes clinical isolates from the respiratory tract, urine, and skin. The collection was started in 2005 and has been enlarged since [14,17,21,25].…”

“…Seven housekeeping genes (gapA, infB, mdh, pgi, phoE, rpoB, tonB) were selected as MLST targets and amplified by PCR as described previously [21]. The strain collection at the Institute of Molecular Biosciences, University of Graz, consists of more than 300 fecal K. oxytoca strains from patients with AAHC, antibiotic-associated diarrhea and IBD, healthy carriers but also includes clinical isolates from the respiratory tract, urine, and skin.…”

“…To investigate the clonal relationship of K. oxytoca isolates from IBD patients and to reveal possible phylogenetic clustering, strains were analyzed using a multilocus sequence typing (MLST) method for K. oxytoca that was recently established by our group [21].…”