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Colonization of Mice With Amoxicillin-Associated Klebsiella variicola Drives Inflammation via Th1 Induction and Treg Inhibition.

ABSTRACT: ?-Lactam antibiotics can increase the resistance and virulence of individual intestinal microorganisms, which may affect host physiology and health. Klebsiella, a crucial gut inhabitant, has been confirmed to be resistant to most ?-lactam antibiotics and contributes to the etiology of inflammatory bowel disease (IBD). In this study, the influence of amoxicillin (AMO) on Klebsiella and its role in colitis was investigated in an antibiotic cocktail (ABx) murine model. The results suggested that a 7-day AMO treatment significantly enriched the abundance of Klebsiella and enhanced serum resistance, antibiotic resistance, and biofilm formation ability of Klebsiella variicola (K. variicola) compared to the wild-type strain in the control group mice. Colonization of mice with the AMO-associated K. variicola could induce Th1 cells and inhibit Treg differentiation to promote inflammation in ABx murine model. In addition, inoculation of AMO-associated K. variicola in dextran sodium sulfate (DSS)-induced colitis murine model mice also confirmed that K. variicola colonization exacerbated inflammation as assessed by increased TNF-?, IFN-?, IL-17a, and disease activity (DAI) levels; decreased colon length and bodyweight; and a disrupted Th1/Treg balance. The results of our study demonstrate that AMO enhances Klebsiella virulence in mice by disrupting the T cell equilibrium to exacerbate colitis, thereby providing a reference for proper antibiotic prescription.

SUBMITTER: Lin H

PROVIDER: S-EPMC7326774 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Colonization of Mice With Amoxicillin-Associated Klebsiella variicola Drives Inflammation via Th1 Induction and Treg Inhibition.

Lin Huai H Wang Qing Q Liu Lei L Chen Zeyou Z Das Ranjit R Zhao Yanhui Y Mao Daqing D Luo Yi Y

Frontiers in microbiology 20200624

β-Lactam antibiotics can increase the resistance and virulence of individual intestinal microorganisms, which may affect host physiology and health. Klebsiella, a crucial gut inhabitant, has been confirmed to be resistant to most β-lactam antibiotics and contributes to the etiology of inflammatory bowel disease (IBD). In this study, the influence of amoxicillin (AMO) on Klebsiella and its role in colitis was investigated in an antibiotic cocktail (ABx) murine model. The results sug ...[more]

PMID: 32670220

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Project description:Klebsiella variicola is a member of the Klebsiella genus and often misidentified as Klebsiella pneumoniae or Klebsiella quasipneumoniae The importance of K. pneumoniae human infections has been known; however, a dearth of relative knowledge exists for K. variicola Despite its growing clinical importance, comprehensive analyses of K. variicola population structure and mechanistic investigations of virulence factors and antibiotic resistance genes have not yet been performed. To address this, we utilized in silico, in vitro, and in vivo methods to study a cohort of K. variicola isolates and genomes. We found that the K. variicola population structure has two distant lineages composed of two and 143 genomes, respectively. Ten of 145 K. variicola genomes harbored carbapenem resistance genes, and 6/145 contained complete virulence operons. While the β-lactam blaLEN and quinolone oqxAB antibiotic resistance genes were generally conserved within our institutional cohort, unexpectedly 11 isolates were nonresistant to the β-lactam ampicillin and only one isolate was nonsusceptible to the quinolone ciprofloxacin. K. variicola isolates have variation in ability to cause urinary tract infections in a newly developed murine model, but importantly a strain had statistically significant higher bladder CFU than the model uropathogenic K. pneumoniae strain TOP52. Type 1 pilus and genomic identification of altered fim operon structure were associated with differences in bladder CFU for the tested strains. Nine newly reported types of pilus genes were discovered in the K. variicola pan-genome, including the first identified P-pilus in Klebsiella spp.IMPORTANCE Infections caused by antibiotic-resistant bacterial pathogens are a growing public health threat. Understanding of pathogen relatedness and biology is imperative for tracking outbreaks and developing therapeutics. Here, we detail the phylogenetic structure of 145 K. variicola genomes from different continents. Our results have important clinical ramifications as high-risk antibiotic resistance genes are present in K. variicola genomes from a variety of geographic locations and as we demonstrate that K. variicola clinical isolates can establish higher bladder titers than K. pneumoniae Differential presence of these pilus genes inK. variicola isolates may indicate adaption for specific environmental niches. Therefore, due to the potential of multidrug resistance and pathogenic efficacy, identification of K. variicola and K. pneumoniae to a species level should be performed to optimally improve patient outcomes during infection. This work provides a foundation for our improved understanding of K. variicola biology and pathogenesis.

Dataset Information

Colonization of Mice With Amoxicillin-Associated Klebsiella variicola Drives Inflammation via Th1 Induction and Treg Inhibition.

Publications

Colonization of Mice With Amoxicillin-Associated <i>Klebsiella variicola</i> Drives Inflammation via Th1 Induction and Treg Inhibition.

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