Genomic Analysis and Molecular Characteristics in Carbapenem-Resistant Klebsiella pneumoniae Strains

Zhao, Sheng; Qiu, Xingyi; Tan, Yiting; Xu, Min; Xu, Xin; Ge, Yulai; Cao, Hongxin; Li, Min; Lin, Yiguang; Zhang, Zhan; Li, Lei; Wu, Qian

doi:10.1007/s00284-022-03093-z

Cited by 2 publications

(2 citation statements)

References 26 publications

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“…In recent years, CRE has been reported in different countries and regions. Numerous investigations have demonstrated that the majority of CRE strains produce carbapenemases, the most prevalent carbapenemase genes were KPC and NDM [ 2 – 5 ]. Since the discovery of bla NDM−1 in Escherichia coli isolated from India in 2008, NDM-producing Enterobacteriaceae have been widely reported throughout the world, and Asia is thought to be the primary epidemic location.…”

Section: Introductionmentioning

confidence: 99%

Epidemiological characteristics of New Delhi Metallo-β-Lactamase-producing Enterobacteriaceae in the Fourth hospital of Hebei Medical University

Zhao

Zhang

et al. 2023

BMC Infect Dis

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The epidemiological characteristics of New Delhi Metallo-β-Lactamase-Producing (NDM) Enterobacteriaceae were analyzed to provide theoretical support for clarifying the distribution characteristics of carbapenem-resistant Enterobacteriaceae (CRE) in the hospital environment and early identification of susceptible patients. From January 2017 to December 2021,42 strains of NDM-producing Enterobacteriaceae were gathered from the Fourth Hospital of Hebei Medical University, primarily Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae. The micro broth dilution method combined with the Kirby-Bauer method was used to determine the minimal inhibitory concentrations (MICs) of antibiotics. The carbapenem phenotype was detected by the modified carbapenem inactivation method (mCIM) and EDTA carbapenem inactivation method (eCIM). Carbapenem genotypes were detected by colloidal gold immunochromatography and real-time fluorescence PCR. The results of antimicrobial susceptibility testing showed that all NDM-producing Enterobacteriaceae were multiple antibiotic resistant, but the sensitivity rate to amikacin was high. Invasive surgery prior to culture, the use of excessive amounts of different antibiotics, the use of glucocorticoids, and ICU hospitalization were clinical characteristics of NDM-producing Enterobacteriaceae infection. Molecular typing of NDM-producing Escherichia coli and Klebsiella pneumoniae was carried out by Multilocus Sequence Typing (MLST), and the phylogenetic trees were constructed. Eight sequence types (STs) and two NDM variants were detected in 11 strains of Klebsiella pneumoniae, primarily ST17, and NDM-1. A total of 8 STs and 4 NDM variants were detected in 16 strains of Escherichia coli, mainly ST410, ST167, and NDM-5. For high-risk patients who have CRE infection, CRE screening should be done as soon as feasible to adopt prompt and efficient intervention measures to prevent outbreaks in the hospital.

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Section: Introductionmentioning

confidence: 99%

Epidemiological characteristics of New Delhi Metallo-β-Lactamase-producing Enterobacteriaceae in the Fourth hospital of Hebei Medical University

Zhao

Zhang

et al. 2023

BMC Infect Dis

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“…These substitutions have been demonstrated to increase the K M parameters for sulfas with less dramatic effects on the K M for pABA, thus conferring a substrate discrimination ability to these DHPS variants, a property absent in the wild-type (WT) enzymes 22 . The second type of sulfa resistance is associated with genes (sul) typically encoded on plasmids found in clinical isolates of such Gram-negative species as E. coli, Acinetobacter baumannii, and K. pneumoniae [24][25][26] . While this type of plasmid-borne sulfa resistance was first reported in the 1950s and 1960s for Shigella and E. coli 27,28 , it was not characterized until 1975.…”

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confidence: 99%

Molecular mechanism of plasmid-borne resistance to sulfonamide antibiotics

et al. 2023

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The sulfonamides (sulfas) are the oldest class of antibacterial drugs and inhibit the bacterial dihydropteroate synthase (DHPS, encoded by folP), through chemical mimicry of its co-substrate p-aminobenzoic acid (pABA). Resistance to sulfa drugs is mediated either by mutations in folP or acquisition of sul genes, which code for sulfa-insensitive, divergent DHPS enzymes. While the molecular basis of resistance through folP mutations is well understood, the mechanisms mediating sul-based resistance have not been investigated in detail. Here, we determine crystal structures of the most common Sul enzyme types (Sul1, Sul2 and Sul3) in multiple ligand-bound states, revealing a substantial reorganization of their pABA-interaction region relative to the corresponding region of DHPS. We use biochemical and biophysical assays, mutational analysis, and in trans complementation of E. coli ΔfolP to show that a Phe-Gly sequence enables the Sul enzymes to discriminate against sulfas while retaining pABA binding and is necessary for broad resistance to sulfonamides. Experimental evolution of E. coli results in a strain harboring a sulfa-resistant DHPS variant that carries a Phe-Gly insertion in its active site, recapitulating this molecular mechanism. We also show that Sul enzymes possess increased active site conformational dynamics relative to DHPS, which could contribute to substrate discrimination. Our results reveal the molecular foundation for Sul-mediated drug resistance and facilitate the potential development of new sulfas less prone to resistance.

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Genomic Analysis and Molecular Characteristics in Carbapenem-Resistant Klebsiella pneumoniae Strains

Cited by 2 publications

References 26 publications

Epidemiological characteristics of New Delhi Metallo-β-Lactamase-producing Enterobacteriaceae in the Fourth hospital of Hebei Medical University

Epidemiological characteristics of New Delhi Metallo-β-Lactamase-producing Enterobacteriaceae in the Fourth hospital of Hebei Medical University

Molecular mechanism of plasmid-borne resistance to sulfonamide antibiotics

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