Overcoming beta-lactam resistance in Pseudomonas aeruginosa by targeting metallo-beta-lactamase VIM-1: a one-microsecond molecular dynamics simulation study
Pseudomonas aeruginosa (P. aeruginosa) is a Gram-negative opportunistic pathogen with a high resistance to beta-lactam antibiotics, mainly due to the production of metallo-beta-lactamase VIM-1 (MBL-VIM-1) enzyme. This study aimed to identify new inhibitors targeting MBL-VIM-1 to restore the efficacy...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-02-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1521391/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832542316081971200 |
|---|---|
| author | Mohammed Salleh M. Ardawi Samar A. Badreddine Muhammad Yasir Muhammad Yasir Aiah M. Khateb Aiah M. Khateb Safaa A. Turkistani Ahmed Afandi Samah O. Noor Adhari Alselmi Adhari Alselmi Vivek Dhar Dwivedi Vivek Dhar Dwivedi Esam I. Azhar Esam I. Azhar |
| author_facet | Mohammed Salleh M. Ardawi Samar A. Badreddine Muhammad Yasir Muhammad Yasir Aiah M. Khateb Aiah M. Khateb Safaa A. Turkistani Ahmed Afandi Samah O. Noor Adhari Alselmi Adhari Alselmi Vivek Dhar Dwivedi Vivek Dhar Dwivedi Esam I. Azhar Esam I. Azhar |
| author_sort | Mohammed Salleh M. Ardawi |
| collection | DOAJ |
| description | Pseudomonas aeruginosa (P. aeruginosa) is a Gram-negative opportunistic pathogen with a high resistance to beta-lactam antibiotics, mainly due to the production of metallo-beta-lactamase VIM-1 (MBL-VIM-1) enzyme. This study aimed to identify new inhibitors targeting MBL-VIM-1 to restore the efficacy of beta-lactam antibiotics. Extensive screening of natural compounds from the COCONUT database was performed to identify the structural analogs of the existing inhibitor of the MBL-VIM-1 protein. The virtual screening process selected four top-performing compounds (CNP0390322, CNP03905695, CNP0079056, and CNP0338283) that exhibited promising docking scores. These compounds were then subjected to re-docking and one-microsecond molecular dynamics (MD) simulations to assess their binding stability and interactions within the MBL-VIM-1 active site. Finally, post-MD simulation calculations were employed to estimate the interaction strengths and compare the efficacy of these compounds against the reference inhibitor. The findings highlighted that these four potent MBL-VIM-1 inhibitors show superior binding affinity and stability, suggesting their potential to combat antibiotic resistance in P. aeruginosa. The identified compounds offer a promising avenue for developing novel therapeutics to restore the efficacy of beta-lactam antibiotics against resistant bacterial strains. Therefore, further in vitro and in vivo studies are warranted to validate their potential. |
| format | Article |
| id | doaj-art-84b7eff9013643329b8b8d4de2358158 |
| institution | Kabale University |
| issn | 2235-2988 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj-art-84b7eff9013643329b8b8d4de23581582025-02-04T06:31:55ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-02-011510.3389/fcimb.2025.15213911521391Overcoming beta-lactam resistance in Pseudomonas aeruginosa by targeting metallo-beta-lactamase VIM-1: a one-microsecond molecular dynamics simulation studyMohammed Salleh M. Ardawi0Samar A. Badreddine1Muhammad Yasir2Muhammad Yasir3Aiah M. Khateb4Aiah M. Khateb5Safaa A. Turkistani6Ahmed Afandi7Samah O. Noor8Adhari Alselmi9Adhari Alselmi10Vivek Dhar Dwivedi11Vivek Dhar Dwivedi12Esam I. Azhar13Esam I. Azhar14Department of Pathological Sciences, Fakeeh College for Medical Sciences, Jeddah, Saudi ArabiaInfection Control Department, Dr. Soliman Fakeeh Hospital, Jeddah, Saudi ArabiaSpecial Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi ArabiaSpecial Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Clinical Laboratory Sciences, College of Applied Medical Science, Taibah University, Medina, Saudi ArabiaMedical Laboratory Sciences, Fakeeh College for Medical Sciences, Jeddah, Saudi ArabiaDiabetic Foot Wound Center, King Fahad Armed Forces Hospital, Jeddah, Saudi ArabiaDepartment of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi ArabiaClinical Sciences Department- MBBS Program, Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia0Dr. Sulaiman Fakeeh Medical Center, Jeddah, Saudi Arabia1Center for Global Health Research, Saveetha Institute of Medical and Technical Sciences, Saveetha Medical College and Hospitals, Saveetha University, Chennai, India2Bioinformatics Research Division, Quanta Calculus, Greater Noida, IndiaSpecial Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi ArabiaPseudomonas aeruginosa (P. aeruginosa) is a Gram-negative opportunistic pathogen with a high resistance to beta-lactam antibiotics, mainly due to the production of metallo-beta-lactamase VIM-1 (MBL-VIM-1) enzyme. This study aimed to identify new inhibitors targeting MBL-VIM-1 to restore the efficacy of beta-lactam antibiotics. Extensive screening of natural compounds from the COCONUT database was performed to identify the structural analogs of the existing inhibitor of the MBL-VIM-1 protein. The virtual screening process selected four top-performing compounds (CNP0390322, CNP03905695, CNP0079056, and CNP0338283) that exhibited promising docking scores. These compounds were then subjected to re-docking and one-microsecond molecular dynamics (MD) simulations to assess their binding stability and interactions within the MBL-VIM-1 active site. Finally, post-MD simulation calculations were employed to estimate the interaction strengths and compare the efficacy of these compounds against the reference inhibitor. The findings highlighted that these four potent MBL-VIM-1 inhibitors show superior binding affinity and stability, suggesting their potential to combat antibiotic resistance in P. aeruginosa. The identified compounds offer a promising avenue for developing novel therapeutics to restore the efficacy of beta-lactam antibiotics against resistant bacterial strains. Therefore, further in vitro and in vivo studies are warranted to validate their potential.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1521391/fullP. aeruginosametallo-beta-lactamaseVIM-1beta-lactam antibioticsdrug discovery |
| spellingShingle | Mohammed Salleh M. Ardawi Samar A. Badreddine Muhammad Yasir Muhammad Yasir Aiah M. Khateb Aiah M. Khateb Safaa A. Turkistani Ahmed Afandi Samah O. Noor Adhari Alselmi Adhari Alselmi Vivek Dhar Dwivedi Vivek Dhar Dwivedi Esam I. Azhar Esam I. Azhar Overcoming beta-lactam resistance in Pseudomonas aeruginosa by targeting metallo-beta-lactamase VIM-1: a one-microsecond molecular dynamics simulation study Frontiers in Cellular and Infection Microbiology P. aeruginosa metallo-beta-lactamase VIM-1 beta-lactam antibiotics drug discovery |
| title | Overcoming beta-lactam resistance in Pseudomonas aeruginosa by targeting metallo-beta-lactamase VIM-1: a one-microsecond molecular dynamics simulation study |
| title_full | Overcoming beta-lactam resistance in Pseudomonas aeruginosa by targeting metallo-beta-lactamase VIM-1: a one-microsecond molecular dynamics simulation study |
| title_fullStr | Overcoming beta-lactam resistance in Pseudomonas aeruginosa by targeting metallo-beta-lactamase VIM-1: a one-microsecond molecular dynamics simulation study |
| title_full_unstemmed | Overcoming beta-lactam resistance in Pseudomonas aeruginosa by targeting metallo-beta-lactamase VIM-1: a one-microsecond molecular dynamics simulation study |
| title_short | Overcoming beta-lactam resistance in Pseudomonas aeruginosa by targeting metallo-beta-lactamase VIM-1: a one-microsecond molecular dynamics simulation study |
| title_sort | overcoming beta lactam resistance in pseudomonas aeruginosa by targeting metallo beta lactamase vim 1 a one microsecond molecular dynamics simulation study |
| topic | P. aeruginosa metallo-beta-lactamase VIM-1 beta-lactam antibiotics drug discovery |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1521391/full |
| work_keys_str_mv | AT mohammedsallehmardawi overcomingbetalactamresistanceinpseudomonasaeruginosabytargetingmetallobetalactamasevim1aonemicrosecondmoleculardynamicssimulationstudy AT samarabadreddine overcomingbetalactamresistanceinpseudomonasaeruginosabytargetingmetallobetalactamasevim1aonemicrosecondmoleculardynamicssimulationstudy AT muhammadyasir overcomingbetalactamresistanceinpseudomonasaeruginosabytargetingmetallobetalactamasevim1aonemicrosecondmoleculardynamicssimulationstudy AT muhammadyasir overcomingbetalactamresistanceinpseudomonasaeruginosabytargetingmetallobetalactamasevim1aonemicrosecondmoleculardynamicssimulationstudy AT aiahmkhateb overcomingbetalactamresistanceinpseudomonasaeruginosabytargetingmetallobetalactamasevim1aonemicrosecondmoleculardynamicssimulationstudy AT aiahmkhateb overcomingbetalactamresistanceinpseudomonasaeruginosabytargetingmetallobetalactamasevim1aonemicrosecondmoleculardynamicssimulationstudy AT safaaaturkistani overcomingbetalactamresistanceinpseudomonasaeruginosabytargetingmetallobetalactamasevim1aonemicrosecondmoleculardynamicssimulationstudy AT ahmedafandi overcomingbetalactamresistanceinpseudomonasaeruginosabytargetingmetallobetalactamasevim1aonemicrosecondmoleculardynamicssimulationstudy AT samahonoor overcomingbetalactamresistanceinpseudomonasaeruginosabytargetingmetallobetalactamasevim1aonemicrosecondmoleculardynamicssimulationstudy AT adharialselmi overcomingbetalactamresistanceinpseudomonasaeruginosabytargetingmetallobetalactamasevim1aonemicrosecondmoleculardynamicssimulationstudy AT adharialselmi overcomingbetalactamresistanceinpseudomonasaeruginosabytargetingmetallobetalactamasevim1aonemicrosecondmoleculardynamicssimulationstudy AT vivekdhardwivedi overcomingbetalactamresistanceinpseudomonasaeruginosabytargetingmetallobetalactamasevim1aonemicrosecondmoleculardynamicssimulationstudy AT vivekdhardwivedi overcomingbetalactamresistanceinpseudomonasaeruginosabytargetingmetallobetalactamasevim1aonemicrosecondmoleculardynamicssimulationstudy AT esamiazhar overcomingbetalactamresistanceinpseudomonasaeruginosabytargetingmetallobetalactamasevim1aonemicrosecondmoleculardynamicssimulationstudy AT esamiazhar overcomingbetalactamresistanceinpseudomonasaeruginosabytargetingmetallobetalactamasevim1aonemicrosecondmoleculardynamicssimulationstudy |