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Peer-reviewedCC BYThe Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale

Plasmid-Mediated AmpC Detection in Escherichia coli and Klebsiella pneumoniae: In Vitro Prevalence and In Silico Inhibitor Design.

  • Muhammad Sarfraz1
  • Aatif Amin2
  • Muhammad Naveed3
  • Mehboob Ahmed1
  • Shahida Hasnain1
  • Saima Naz2
  • Mohsin Khurshid4
  • Mohsin Tassawar Cheema5
  • Samman Ikram2
  • Ajaz Ahmad6
6 affiliations
  1. 1Institute of Microbiology and Molecular Genetics University of the Punjab Quaid-e-Azam Campus Lahore 54590 Pakistan pu.edu.pk.
  2. 2Department of Microbiology Faculty of Science and Technology University of Central Punjab Lahore 54000 Pakistan ucp.edu.pk.
  3. 3Department of Biotechnology Faculty of Science and Technology University of Central Punjab Lahore 54000 Pakistan ucp.edu.pk.
  4. 4Institute of Microbiology Government College University Faisalabad Pakistan gcu.edu.pk.
  5. 5Department of Cardiothoracic Surgery School of Medicine University of Pittsburgh Pittsburgh 15232 Pennsylvania USA pitt.edu.
  6. 6Department of Clinical Pharmacy College of Pharmacy King Saud University Riyadh 11451 Saudi Arabia ksu.edu.sa.
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Abstract

Objectives

This study investigated the prevalence of AmpC beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in clinical specimens collected in Lahore, Pakistan, and aimed to identify potential inhibitors targeting AmpC beta-lactamases.Methods

A total of 17,500 clinical specimens were collected from June 2018 to June 2021 and analyzed for E. coli and K. pneumoniae. These isolates underwent phenotypic identification using microscopy and the API 20E kit. AmpC beta-lactamase production was initially screened using cefoxitin disk diffusion and inhibitor-based methods, while the presence of plasmid-borne AmpC genes (CIT, EBC, and DHA) was confirmed by PCR. Additionally, the study used computational drug discovery techniques to screen for oxadiazole, quinazolinone, and sulfonylurea derivatives as potential inhibitors of the AmpC protein.Results

Our data showed high antibiotic resistance rates among E. coli and K. pneumoniae isolates: 74.5% were resistant to cefotaxime and ceftazidime, and 45% to cefoxitin. PCR testing revealed that the CIT gene was the most prevalent in both E. coli (65.4%) and K. pneumoniae (63%), while other genes (EBC and DHA) and combinations were also present (p < 0.005). Using computational drug discovery, several compound libraries were screened against the AmpC protein. Tolbutamide showed the most promising results, with strong binding affinity and favorable drug-like properties.Conclusion

Plasmid-mediated AmpC beta-lactamase-producing E. coli and K. pneumoniae were highly prevalent, with the CIT genotype predominating among clinical isolates. Computational screening identified Tolbutamide as a promising lead compound, warranting further experimental validation before therapeutic application.

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Cite

BibTeXRIS
BibTeX
@article{sarfraz2026plasmidmediated,
  title = {{Plasmid-Mediated AmpC Detection in Escherichia coli and Klebsiella pneumoniae: In Vitro Prevalence and In Silico Inhibitor Design.}},
  author = {Muhammad Sarfraz and Aatif Amin and Muhammad Naveed and Mehboob Ahmed and Shahida Hasnain and Saima Naz and Mohsin Khurshid and Mohsin Tassawar Cheema and Samman Ikram and Ajaz Ahmad},
  journal = {The Canadian journal of infectious diseases \& medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale},
  year = {2026},
  month = oct,
  doi = {10.1155/cjid/1023166},
  url = {https://europepmc.org/article/MED/42959740},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Plasmid-Mediated AmpC Detection in Escherichia coli and Klebsiella pneumoniae: In Vitro Prevalence and In Silico Inhibitor Design.
AU  - Muhammad Sarfraz
AU  - Aatif Amin
AU  - Muhammad Naveed
AU  - Mehboob Ahmed
AU  - Shahida Hasnain
AU  - Saima Naz
AU  - Mohsin Khurshid
AU  - Mohsin Tassawar Cheema
AU  - Samman Ikram
AU  - Ajaz Ahmad
PY  - 2026
DA  - 2026/10/29
JO  - The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale
DO  - 10.1155/cjid/1023166
UR  - https://europepmc.org/article/MED/42959740
AB  - Objectives  This study investigated the prevalence of AmpC beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in clinical specimens collected in Lahore, Pakistan, and aimed to identify potential inhibitors targeting AmpC beta-lactamases.Methods  A total of 17,500 clinical specimens were collected from June 2018 to June 2021 and analyzed for E. coli and K. pneumoniae. These isolates underwent phenotypic identification using microscopy and the API 20E kit. AmpC beta-lactamase production was initially screened using cefoxitin disk diffusion and inhibitor-based methods, while the presence of plasmid-borne AmpC genes (CIT, EBC, and DHA) was confirmed by PCR. Additionally, the study used computational drug discovery techniques to screen for oxadiazole, quinazolinone, and sulfonylurea derivatives as potential inhibitors of the AmpC protein.Results  Our data showed high antibiotic resistance rates among E. coli and K. pneumoniae isolates: 74.5% were resistant to cefotaxime and ceftazidime, and 45% to cefoxitin. PCR testing revealed that the CIT gene was the most prevalent in both E. coli (65.4%) and K. pneumoniae (63%), while other genes (EBC and DHA) and combinations were also present (p < 0.005). Using computational drug discovery, several compound libraries were screened against the AmpC protein. Tolbutamide showed the most promising results, with strong binding affinity and favorable drug-like properties.Conclusion  Plasmid-mediated AmpC beta-lactamase-producing E. coli and K. pneumoniae were highly prevalent, with the CIT genotype predominating among clinical isolates. Computational screening identified Tolbutamide as a promising lead compound, warranting further experimental validation before therapeutic application.
SN  - 1712-9532
SN  - 1918-1493
ER  -