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Interactions of Klebsiella pneumoniae with the innate immune system vary in relation to clone and resistance phenotype.

ABSTRACT: Apart from inadequate antimicrobial treatment, specific virulence factors contribute to the high attributable mortality of infections caused by multidrug-resistant (MDR) Klebsiella pneumoniae. We explored the roles of MDR and clones as virulence determinants of K. pneumoniae and their interaction with innate immunity. Twenty isolates were studied and characterized by resistance phenotype and multilocus sequence type (MLST). Human peripheral blood mononuclear cells (PBMCs) were stimulated for the production of proinflammatory cytokines by live and heat-killed isolates and plasmid DNA; modulation by cellular pathway inhibitors was explored. Survival of 30 mice was recorded after intraperitoneal challenge with susceptible and K. pneumoniae carbapenemase (KPC)-producing isolates. Splenocytes of mice were stimulated for the production of pro- and anti-inflammatory cytokines. Isolates were divided into different patterns of production of tumor necrosis factor alpha (TNF-?) and interleukin-1? (IL-1?) poststimulation in relation to both the MLST clone and resistance phenotype. The sequence type 383 (ST383) clone producing Verona integron-encoded metallo-?-lactamase (VIM) stimulated high production of both TNF-? and IL-1?. Clone ST17 producing KPC elicited low TNF-? production; this was reversed by Toll-like receptor 9 (TLR9) antagonists, indicating an effect of plasmid DNA. This isolate was linked with early death of mice compared to high-TNF-?-producing isolates. We conclude that KPC-producing isolates seem to be highly virulent in a low-TNF-?-release environment, suggesting an immunoparalysis induction mechanism. KPC plasmids may directly contribute to the immune system stimulation.

SUBMITTER: Pantelidou IM

PROVIDER: S-EPMC4604363 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Interactions of Klebsiella pneumoniae with the innate immune system vary in relation to clone and resistance phenotype.

Pantelidou Iliana-Maria IM Galani Irene I Georgitsi Marianna M Daikos George L GL Giamarellos-Bourboulis Evangelos J EJ

Antimicrobial agents and chemotherapy 20150908 11

Apart from inadequate antimicrobial treatment, specific virulence factors contribute to the high attributable mortality of infections caused by multidrug-resistant (MDR) Klebsiella pneumoniae. We explored the roles of MDR and clones as virulence determinants of K. pneumoniae and their interaction with innate immunity. Twenty isolates were studied and characterized by resistance phenotype and multilocus sequence type (MLST). Human peripheral blood mononuclear cells (PBMCs) were stimulated for the ...[more]

PMID: 26349819

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Project description:International high-risk clones of Klebsiella pneumoniae are among the most common nosocomial pathogens. Increased diversity of plasmid-encoded antimicrobial resistance genes facilitates spread of these clones causing significant therapeutic difficulties. The purpose of our study was to investigate fluoroquinolone resistance in extended-spectrum beta-lactamase (ESBL)-producing strains, including four K. pneumoniae and a single K. oxytoca, isolated from blood cultures in Hungary. Whole-genome sequencing and molecular typing including multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed in selected strains. Gene expression of plasmid-mediated quinolone resistance determinants (PMQR) was investigated by quantitative-PCR. MLST revealed that three K. pneumoniae strains belonged to ST11 and one to ST307 whereas K. oxytoca belonged to ST52. The isolates harbored different ?-lactamase genes, however, all K. pneumoniae uniformly carried bla CTX-M-15. The K. pneumoniae isolates exhibited resistance to fluoroquinolones and carried various PMQR genes namely, two ST11 strains harbored qnrB4, the ST307 strain harbored qnrB1 and all K. pneumoniae harbored oqxAB efflux pump. Levofloxacin and moxifloxacin MIC values of K. pneumoniae ST11 and ST307 clones correlated with qnr and oqxAB expression levels. The qnrA1 carrying K. oxytoca ST52 exhibited reduced susceptibility to fluoroquinolones. The maintained expression of qnr genes in parallel with chromosomal mutations indicate an additional protective role of Qnr proteins that can support dissemination of high-risk clones. During development of high-level fluoroquinolone resistance, high-risk clones retain fitness thus, enabling them for dissemination in hospital environment. Based on our knowledge this is the first report of ST307 clone in Hungary, that is emerging as a potential high-risk clone worldwide. High-level fluoroquinolone resistance in parallel with upregulated PMQR gene expression are linked to high-risk K. pneumoniae clones.

Dataset Information

Interactions of Klebsiella pneumoniae with the innate immune system vary in relation to clone and resistance phenotype.

Publications

Interactions of Klebsiella pneumoniae with the innate immune system vary in relation to clone and resistance phenotype.

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