Full title: Identification of potential drug targets against carbapenem resistant Enterobacteriaceae (CRE) strains using in silico gene network analysis

Baishya, Somorita; Banik, Sheuli Kangsa; Talukdar, Anupam Das; Anbarasu, Anand; Bhattacharjee, Amitabha; Choudhury, Manabendra Dutta

doi:10.1016/j.genrep.2018.12.002

Cited by 9 publications

(8 citation statements)

References 63 publications

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“…The issues of antimicrobial resistance specifically towards carbapenems require immediate attention. Developing a holistic model to visualize and decipher the role of genes of secondary resistome along with the primary resistance genes is explicit [ 4 , 22 ]. Genes associated with CRE is considered in this study.…”

Section: Discussionmentioning

confidence: 99%

“…The report published on gene network analysis of CRE harboring bla NDM unveiled that apart from the genes primarily associated with CRE like bla NDM , ampC some other genes, that are apparently non-essential in imparting carbapenem resistance, play influential role in the system [ 22 ]. These genes help the bacteria to survive under therapeutic stress of carbapenems and cephalosporins.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional expression of secondary resistance genes ccdB and repA2 is enhanced in presence of cephalosporin and carbapenem in Escherichia coli

et al. 2021

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Background The issue of carbapenem resistance in E.coli is very concerning and it is speculated that cumulative effect of both primary resistance genes and secondary resistance genes that act as helper to the primary resistance genes are the reason behind their aggravation. Therefore, here we attempted to find the role of two secondary resistance genes (SRG) ccdB and repA2 in carbapenem resistance in E. coli (CRE). In this context influential genes belonging to secondary resistome that act as helper to the primary resistance genes like blaNDM and blaCTX-M in aggravating β-lactam resistance were selected from an earlier reported in silico study. Transcriptional expression of the selected genes in clinical isolates of E.coli that were discretely harboring blaNDM-1, blaNDM-4, blaNDM-5, blaNDM-7 and blaCTX-M-15 with and without carbapenem and cephalosporin stress (2 μg/ml) was determined by real time PCR. Cured mutants sets that were lacking (i) primary resistance genes, (ii) secondary resistance genes and (iii) both primary and secondary resistance genes were prepared by SDS treatment. These sets were then subjected to antibiotic susceptibility testing by Kirby Bauer disc diffusion method. Results Out of the 21 genes reported in the in silico study, 2 genes viz.repA2 and ccdB were selected for transcriptional expression analysis. repA2, coding replication regulatory protein, was downregulated in response to carbapenems and cephalosporins. ccdB, coding for plasmid maintenance protein, was also downregulated in response to carbapenems except imipenem and cephalosporins. Following plasmid elimination assay increase in diameter of zone of inhibition under stress of both antibiotics was observed as compared to uncured control hinting at the reversion of antibiotic susceptibility by the-then resistant bacteria. Conclusion SRGs repA2 and ccdB help sustenance of blaNDM and blaCTX-M under carbapenem and cephalosporin stress.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transcriptional expression of secondary resistance genes ccdB and repA2 is enhanced in presence of cephalosporin and carbapenem in Escherichia coli

et al. 2021

Self Cite

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show abstract

“…The issues of antimicrobial resistance speci cally towards carbapenems require immediate attention. Developing a holistic model to visualize and decipher the role of genes of secondary resistome along with the primary resistance genes is explicit (4,22). Genes associated with CRE is considered in this study.…”

Section: Discussionmentioning

confidence: 99%

“…From the 21 genes that had been streamlined from in silico analysis (22) two genes viz. ccdB (cluster 19) involved with plasmid maintenance protein and repA2 (cluster 33) associated with replication regulatory protein have been ltered out for in vitro transcriptional analysis.…”

Section: Discussionmentioning

confidence: 99%

“…The report published on gene network analysis of CRE harboring bla NDM unveiled that apart from the genes primarily associated with CRE like bla NDM , ampC some other genes, that are apparently nonessential in imparting carbapenem resistance, play in uential role in the system (22). These genes help the bacteria to survive under therapeutic stress of carbapenems and cephalosporins.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional expression of secondary resistance genes ccdB and repA2 is enhanced in presence of cephalosporin and carabapenem in Escherichia coli

Baishya

Deshamukhya

Wangkheimayum

et al. 2020

Preprint

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Background: The issue of carbapenem resistance in E.coli is very concerning and it is speculated that cumulative effect of both primary resistance genes and secondary resistance genes that act as helper to the primary resistance genes are the reason behind their aggravation. Therefore, here we attempted to find the role of two secondary resistance genes (SRG) ccdB and repA2 in carbapenem resistance in E. coli (CRE).Methods: Influential genes belonging to secondary resistome that act as helper to the primary resistance genes like blaNDM and blaCTX-M in aggravating β-lactam resistance were selected from an earlier reported in silico study. Transcriptional expression of the selected genes in clinical isolates of E.coli that were discretely harboring blaNDM-1, blaNDM-4, blaNDM-5, blaNDM-7 and blaCTX-M-15 with and without carbapenem and cephalosporin stress (2µg/ml) was determined by real time PCR. Cured mutants sets that were lacking (i) primary resistance genes, (ii) secondary resistance genes and (iii) both primary and secondary resistance genes were prepared by SDS treatment. These sets were then subjected to antibiotic susceptibility testing by Kirby Bauer disc diffusion method.Results: Out of the 21 genes reported in the in silico study, 2 genes viz. repA2 and ccdB were selected for transcriptional expression analysis. repA2, coding replication regulatory protein, was downregulated in response to carbapenems and cephalosporins. ccdB, coding for plasmid maintenance protein, was also downregulated in response to carbapenems except imipenem and cephalosporins. Following plasmid elimination assay increase in diameter of zone of inhibition under stress of both antibiotics was observed as compared to uncured control hinting at the reversion of antibiotic susceptibility by the-then resistant bacteria. Conclusion: SRGs repA2 and ccdB help sustenance of blaNDM and blaCTX-M under carbapenem and cephalosporin stress.

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Molecular Docking in Drug Designing and Metabolism

Saikia

Puzari

Chetia

2023

Industrial Microbiology and Biotechnology

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Full title: Identification of potential drug targets against carbapenem resistant Enterobacteriaceae (CRE) strains using in silico gene network analysis

Cited by 9 publications

References 63 publications

Transcriptional expression of secondary resistance genes ccdB and repA2 is enhanced in presence of cephalosporin and carbapenem in Escherichia coli

Transcriptional expression of secondary resistance genes ccdB and repA2 is enhanced in presence of cephalosporin and carbapenem in Escherichia coli

Transcriptional expression of secondary resistance genes ccdB and repA2 is enhanced in presence of cephalosporin and carabapenem in Escherichia coli

Molecular Docking in Drug Designing and Metabolism

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