Correction: Biochemical Characterization of CTX-M-15 from Enterobacter cloacae and Designing a Novel Non-β-Lactam-β-Lactamase Inhibitor

Faheem, Mohammad; Rehman, Md. Tabish; Danishuddin, Mohd; Khan, Asad

doi:10.1371/annotation/049bf1aa-d866-471f-95c1-5939d4461f8c

Cited by 10 publications

(4 citation statements)

References 50 publications

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“…Vice-versa, the emergence of this lineage may be influenced by the reduction of fluoroquinolone use. With respect to the observed differences for ampicillin-sulbactam, others have noted that bla CTX-M-15 genes (or isolates harboring these determinants) are associated with increased frequency of resistance compared to isolates carrying the bla CTX-M-27 gene (Faheem et al, 2013;Matsumura et al, 2015). This is consistent with our results given the respective preponderance of these enzymes in ST131 vs. ST38.…”

Section: Discussionsupporting

confidence: 91%

Genomic Surveillance of Ceftriaxone-Resistant Escherichia coli in Western New York Suggests the Extended-Spectrum β-Lactamase blaCTX-M-27 Is Emerging on Distinct Plasmids in ST38

et al. 2020

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Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae pose significant treatment and infection prevention challenges. Escherichia coli sequence type (ST) 131 associated with the bla CTX-M-15 gene has been the dominant lineage of ESBL-producing E. coli in the US and worldwide. In this study, our objective was to determine the β-lactamase profile, means of dissemination, prevalence, and the clonal identity of ESBL-producing E. coli in our region of Western New York. Whole-genome SNP-based phylogenomics was used to assess 89 ceftriaxone-resistant (CTR) E. coli. Isolates were collected from both inpatients and outpatients and from urine and sterile-sites over a 2 month period in 2017 or throughout the year, respectively. ST131 was the predominant ST (46.0%), followed by ST38 (15.7%). The bla CTX-M-15 gene was commonly found in 53.7% of ST131 isolates, whereas the bla CTX-M-27 gene was found in 26.8% of ST131, though was significantly associated with ST38, and was found in 71.4% of those strains. When compared to ST131, ST38 E. coli exhibited increased frequency of resistance to nitrofurantoin and decreased frequency of resistance to ciprofloxacin and ampicillin-sulbactam. Using Nanopore long-read sequencing technology, an analysis of the ESBL genetic context showed that the bla CTX-M-15 gene was chromosomal in 68.2% of ST131, whereas the bla CTX-M-27 gene was plasmid-borne in all ST131 and 90% of ST38 isolates. Notably, the bla CTX-M-27 gene in ST38 resided on highly-related (99.0-100.0% identity and 65.0-98.0% query coverage) conjugative IncF plasmids of distinct plasmid multi-locus sequence types (pMLSTs) from those in ST131. Furthermore, ST131 and ST38 were found to harbor different antibiotic resistance gene and virulence factor profiles. These findings raise the possibility of an emerging ESBL-producing E. coli lineage in our region.

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Section: Discussionsupporting

confidence: 91%

Genomic Surveillance of Ceftriaxone-Resistant Escherichia coli in Western New York Suggests the Extended-Spectrum β-Lactamase blaCTX-M-27 Is Emerging on Distinct Plasmids in ST38

et al. 2020

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“…Therefore, the antibiotics resistance necessitates the need for identifying novel inhibitors that lack the β-lactam ring [3]. The advantage of non-β-lactam inhibitors lies in the fact that such inhibitors cannot be easily hydrolyzed by β-lactamases and can escape the defense mechanisms of resistant bacteria [4].…”

Section: Introductionmentioning

confidence: 99%

High-Throughput Virtual Screening, Molecular Dynamics Simulation, and Enzyme Kinetics Identified ZINC84525623 as a Potential Inhibitor of NDM-1

Rehman

Alajmi

Hussain

et al. 2019

IJMS

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The bacteria expressing New Delhi Metallo-β-lactamase-1 (NDM-1) can hydrolyze all β-lactam antibiotics including carbapenems, causing multi-drug resistance. The worldwide emergence and dissemination of gene blaNDM-1 (produces NDM-1) in hospital and community settings, rising problems for public health. Indeed, there is an urgent need for NDM-1 inhibitors to manage antibiotic resistance. Here, we have identified novel non-β-lactam ring-containing inhibitors of NDM-1 by applying a high-throughput virtual screening of lead-like subset of ZINC database. The screened compounds were followed for the molecular docking, the molecular dynamics simulation, and then enzyme kinetics assessment. The adopted screening procedure funnels out five novel inhibitors of NDM-1 including ZINC10936382, ZINC30479078, ZINC41493045, ZINC7424911, and ZINC84525623. The molecular mechanics-generalized born surface area and molecular dynamics (MD) simulation showed that ZINC84525623 formed the most stable complex with NDM-1. Furthermore, analyses of the binding pose after MD simulation revealed that ZINC84525623 formed two hydrogen bonds (electrostatic and hydrophobic interaction) with key amino acid residues of the NDM-1 active site. The docking binding free energy and docking binding constant for the ZINC84525623 and NDM-1 interaction were estimated to be −11.234 kcal/mol, and 1.74 × 108 M−1 respectively. Steady-state enzyme kinetics in the presence of ZINC84525623 show the decreased catalytic efficiency (i.e., kcat/Km) of NDM-1 on various antibiotics. The findings of this study would be helpful in identifying novel inhibitors against other β-lactamases from a pool of large databases. Furthermore, the identified inhibitor (ZINC84525623) could be developed as efficient drug candidates.

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“…This scarcity and necessity motivated us to identify novel non-β-lactam ring-containing inhibitors against NDM-1. The advantage of using non-β-lactam corecontaining inhibitors is that they are not hydrolyzed and inactivated by the present defense mechanisms of the antibiotic-resistant bacteria [25]. The identification of non-β-lactam core-containing inhibitors is an optimistic way to maintain the efficacy of β-lactam antibiotics.…”

Section: Discussionmentioning

confidence: 99%

Risedronate and Methotrexate Are High-Affinity Inhibitors of New Delhi Metallo-β-Lactamase-1 (NDM-1): A Drug Repurposing Approach

et al. 2022

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Bacteria expressing New Delhi metallo-β-lactamase-1 (NDM-1) can hydrolyze β-lactam antibiotics (penicillins, cephalosporins, and carbapenems) and, thus, mediate multidrug resistance. The worldwide dissemination of NDM-1 poses a serious threat to public health, imposing a huge economic burden in the development of new antibiotics. Thus, there is an urgent need for the identification of novel NDM-1 inhibitors from a pool of already-known drug molecules. Here, we screened a library of FDA-approved drugs to identify novel non-β-lactam ring-containing inhibitors of NDM-1 by applying computational as well as in vitro experimental approaches. Different steps of high-throughput virtual screening, molecular docking, molecular dynamics simulation, and enzyme kinetics were performed to identify risedronate and methotrexate as the inhibitors with the most potential. The molecular mechanics/generalized Born surface area (MM/GBSA) and molecular dynamics (MD) simulations showed that both of the compounds (risedronate and methotrexate) formed a stable complex with NDM-1. Furthermore, analyses of the binding pose revealed that risedronate formed two hydrogen bonds and three electrostatic interactions with the catalytic residues of NDM-1. Similarly, methotrexate formed four hydrogen bonds and one electrostatic interaction with NDM-1’s active site residues. The docking scores of risedronate and methotrexate for NDM-1 were –10.543 kcal mol−1 and −10.189 kcal mol−1, respectively. Steady-state enzyme kinetics in the presence of risedronate and methotrexate showed a decreased catalytic efficiency (i.e., kcat/Km) of NDM-1 on various antibiotics, owing to poor catalytic proficiency and affinity. The results were further validated by determining the MICs of imipenem and meropenem in the presence of risedronate and methotrexate. The IC50 values of the identified inhibitors were in the micromolar range. The findings of this study should be helpful in further characterizing the potential of risedronate and methotrexate to treat bacterial infections.

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Correction: Biochemical Characterization of CTX-M-15 from Enterobacter cloacae and Designing a Novel Non-β-Lactam-β-Lactamase Inhibitor

Cited by 10 publications

References 50 publications

Genomic Surveillance of Ceftriaxone-Resistant Escherichia coli in Western New York Suggests the Extended-Spectrum β-Lactamase blaCTX-M-27 Is Emerging on Distinct Plasmids in ST38

Genomic Surveillance of Ceftriaxone-Resistant Escherichia coli in Western New York Suggests the Extended-Spectrum β-Lactamase blaCTX-M-27 Is Emerging on Distinct Plasmids in ST38

High-Throughput Virtual Screening, Molecular Dynamics Simulation, and Enzyme Kinetics Identified ZINC84525623 as a Potential Inhibitor of NDM-1

Risedronate and Methotrexate Are High-Affinity Inhibitors of New Delhi Metallo-β-Lactamase-1 (NDM-1): A Drug Repurposing Approach

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