Dataset Information

In vivo Acquisition of Carbapenemase Gene blaKPC-2 in Multiple Species of Enterobacteriaceae through Horizontal Transfer of Insertion Sequence or Plasmid.

ABSTRACT: Objectives: Current worldwide spread of carbapenem resistance in Enterobacteriaceae constitutes a critical public health threat. This study aims to investigate how carbapenem resistance is acquired in Enterobacteriaceae in patients during antimicrobial therapy. Methods: Clinical strains from the same anatomical site of the same patients that converted from carbapenem-susceptible to resistant during antimicrobial therapy and showed identical or similar PFGE patterns were identified. The similarly sized plasmids carried by the susceptible and resistant strains, the latter containing the carbapenemase genes, were sequenced and analyzed. Results: Paired strains were identified from four patients: three had neurosurgical conditions while the other had acute exacerbation of COPD. Two pairs of Klebsiella pneumoniae (KP1-S/R and KP2-S/R, S and R indicating susceptible and resistant strains, respectively), one pair of Morganella morganii (MM-S/R) and one pair of Enterobacter aerogenes (EA-S/R) were collected. All four carbapenem-resistant strains carried plasmids harboring blaKPC-2. Compared with the similarly sized plasmids in KP1-S and KP2-S, an insertion sequence that includes ISKpn6-like, blaKPC-2 and ISKpn8 was noted in pKP1-R and pKP2-R. Strains MM-R and EA-R had blaKPC-2-carrying plasmids not resembling plasmids in strains MM-S and EA-S suggesting their new acquisition while on therapy. Conclusions: Enterobacteriaceae can acquire carbapenem resistance during antimicrobial therapy through horizontal transfer of an insertion sequence or plasmid.

SUBMITTER: Ding B

PROVIDER: S-EPMC5073136 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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In vivo Acquisition of Carbapenemase Gene blaKPC-2 in Multiple Species of Enterobacteriaceae through Horizontal Transfer of Insertion Sequence or Plasmid.

Ding Baixing B Shen Zhen Z Hu Fupin F Ye Meiping M Xu Xiaogang X Guo Qinglan Q Wang Minggui M

Frontiers in microbiology 20161021

Objectives: Current worldwide spread of carbapenem resistance in Enterobacteriaceae constitutes a critical public health threat. This study aims to investigate how carbapenem resistance is acquired in Enterobacteriaceae in patients during antimicrobial therapy. Methods: Clinical strains from the same anatomical site of the same patients that converted from carbapenem-susceptible to resistant during antimicrobial therapy and showed identical or similar PFGE patterns were identified. ...[more]

PMID: 27818649

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Project description:UNLABELLED:Bacterial conjugation constitutes a major horizontal gene transfer mechanism for the dissemination of antibiotic resistance genes among human pathogens. Antibiotic resistance spread could be halted or diminished by molecules that interfere with the conjugation process. In this work, synthetic 2-alkynoic fatty acids were identified as a novel class of conjugation inhibitors. Their chemical properties were investigated by using the prototype 2-hexadecynoic acid and its derivatives. Essential features of effective inhibitors were the carboxylic group, an optimal long aliphatic chain of 16 carbon atoms, and one unsaturation. Chemical modification of these groups led to inactive or less-active derivatives. Conjugation inhibitors were found to act on the donor cell, affecting a wide number of pathogenic bacterial hosts, including Escherichia, Salmonella, Pseudomonas, and Acinetobacter spp. Conjugation inhibitors were active in inhibiting transfer of IncF, IncW, and IncH plasmids, moderately active against IncI, IncL/M, and IncX plasmids, and inactive against IncP and IncN plasmids. Importantly, the use of 2-hexadecynoic acid avoided the spread of a derepressed IncF plasmid into a recipient population, demonstrating the feasibility of abolishing the dissemination of antimicrobial resistances by blocking bacterial conjugation. IMPORTANCE:Diseases caused by multidrug-resistant bacteria are taking an important toll with respect to human morbidity and mortality. The most relevant antibiotic resistance genes come to human pathogens carried by plasmids, mainly using conjugation as a transmission mechanism. Here, we identified and characterized a series of compounds that were active against several plasmid groups of clinical relevance, in a wide variety of bacterial hosts. These inhibitors might be used for fighting antibiotic-resistance dissemination by inhibiting conjugation. Potential inhibitors could be used in specific settings (e.g., farm, fish factory, or even clinical settings) to investigate their effect in the eradication of undesired resistances.

Dataset Information

In vivo Acquisition of Carbapenemase Gene blaKPC-2 in Multiple Species of Enterobacteriaceae through Horizontal Transfer of Insertion Sequence or Plasmid.

Publications

<i>In vivo</i> Acquisition of Carbapenemase Gene <i>bla</i><sub>KPC-2</sub> in Multiple Species of <i>Enterobacteriaceae</i> through Horizontal Transfer of Insertion Sequence or Plasmid.

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