Genome-wide association study of Klebsiella pneumoniae identifies variations linked to carbapenems resistance
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Genome-wide association study of Klebsiella pneumoniae identifies variations linked to carbapenems resistance. / Pei, Na; Sun, Wanying; He, Jingxuan; Li, Yanming; Chen, Xia; Liang, Tianzhu; Kristiansen, Karsten; Liu, Wenen; Li, Junhua.
I: Frontiers in Microbiology, Bind 13, 997769, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Genome-wide association study of Klebsiella pneumoniae identifies variations linked to carbapenems resistance
AU - Pei, Na
AU - Sun, Wanying
AU - He, Jingxuan
AU - Li, Yanming
AU - Chen, Xia
AU - Liang, Tianzhu
AU - Kristiansen, Karsten
AU - Liu, Wenen
AU - Li, Junhua
PY - 2022
Y1 - 2022
N2 - Klebsiella pneumoniae (KP) is one of the microorganisms that can acquire carbapenem-resistance (CR), and few antimicrobial therapy options exist for infections caused by Carbapenem-Resistant KP (CRKP). In recent years, with the increase of carbapenem resistance rates, treating CRKP has become a serious public health threat in clinical practice. We have collected 2,035 clinical KP isolates from a tertiary hospital in China. Whole genome sequencing data coupled with their binary antimicrobial susceptibility testing data were obtained to conduct the genome-wide association study using a bayesian-based method, including single nucleotide polymorphisms (SNPs) and genes. We identified 28 and 37 potential maker genes associated with imipenem and meropenem resistance, respectively. Among which 19 of them were selected in both drugs by genome-wide association study (GWAS), 11 genes among them were simultaneously validated in independent datasets. These genes were likely related to biofilm formation, efflux pump, and DNA repairing. Moreover, we identified 13 significant CR related SNPs in imipenem or meropenem, with one SNP located in the non-coding region and validated in the independent datasets. Our study indicates complex mechanisms of carbapenems resistance and further investigation of CRKP-related factors are warranted to better understand their contributions to carbapenems resistance. These identified biomarkers may provide targets for future drug interventions or treatments.
AB - Klebsiella pneumoniae (KP) is one of the microorganisms that can acquire carbapenem-resistance (CR), and few antimicrobial therapy options exist for infections caused by Carbapenem-Resistant KP (CRKP). In recent years, with the increase of carbapenem resistance rates, treating CRKP has become a serious public health threat in clinical practice. We have collected 2,035 clinical KP isolates from a tertiary hospital in China. Whole genome sequencing data coupled with their binary antimicrobial susceptibility testing data were obtained to conduct the genome-wide association study using a bayesian-based method, including single nucleotide polymorphisms (SNPs) and genes. We identified 28 and 37 potential maker genes associated with imipenem and meropenem resistance, respectively. Among which 19 of them were selected in both drugs by genome-wide association study (GWAS), 11 genes among them were simultaneously validated in independent datasets. These genes were likely related to biofilm formation, efflux pump, and DNA repairing. Moreover, we identified 13 significant CR related SNPs in imipenem or meropenem, with one SNP located in the non-coding region and validated in the independent datasets. Our study indicates complex mechanisms of carbapenems resistance and further investigation of CRKP-related factors are warranted to better understand their contributions to carbapenems resistance. These identified biomarkers may provide targets for future drug interventions or treatments.
KW - Klebsiella pneumoniae
KW - carbapenems
KW - genome-wide association study
KW - drug resistance
KW - variations
KW - GENE
KW - ENTEROBACTERIACEAE
KW - ALGORITHM
KW - SPECTRUM
KW - BIOFILM
KW - ENCODES
KW - PROTEIN
U2 - 10.3389/fmicb.2022.997769
DO - 10.3389/fmicb.2022.997769
M3 - Journal article
C2 - 36386631
VL - 13
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
SN - 1664-302X
M1 - 997769
ER -
ID: 329701320