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<p>Salmonella bacteria cause an infection called salmonellosis. Nontyphoidal salmonellae (NTS) are significant contributors to foodborne infections that must be reported. Infections caused by NTS affects both the blood stream and other sites that are free from bacteria and can lead to severe and potentially fatal invasive diseases. Ceftriaxone is a third-generation cephalosporin antibiotic used to treat bacterial infections like NTS. The antimicrobial properties of ceftriaxone stem from its capacity to hinder cell wall formation by interacting with penicillin-binding proteins (PBPs). The therapeutic issue lies in the resistance of NTS to ceftriaxone, thereby increasing the need for innovative antimicrobial medications. The primary goal of this research is to identify previously unknown ceftriaxone derivatives that could potentially serve as effective treatments for NTS, while also exhibiting a favorable pharmacokinetic profile. Retrieval of the target protein PBP was done from the Protein databank, and the 3D chemical structures were accessed through the PubChem database. The Lipinski rule of five and ADME prediction using Biovia Discovery Studio were employed to evaluate ceftriaxone and its similar structures. Extended analysis was completed by utilizing molecular dynamics simulation (MDS) studies and metabolic reactivity prediction via Xenosite server. In the docking study, it was shown that PL-1 and PL-2 possess inhibitory potential against PBP, with libdock scores of 126.6 and 124.10, respectively, higher than the control drug ceftriaxone's score of 95.4. The MDS molecular dynamics simulations demonstrated that the PL-1 complex with PBP exhibited similar stability when compared to the control ceftriaxone complex, showing average RMSD values of 10&#xa0;Å and 10.5&#xa0;Å, respectively. This outcome implies that PL-1 deserves additional scrutiny in the field of research. By considering the inhibitory effects of compound PL-1, it is plausible to conclude that the identified lead may exhibit an outstanding capacity to combat microbial pathogens.</p>

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Computational investigation for the analysis and prediction of chemical compounds to overcome drug resistance in Non Typhoidal Salmonella (NTS)

  • 期刊论文

  • 发表日期：

    2025年3月13日

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  • Amna Tamimi,
  • Mantasha Khan,
  • Masoom Raza Siddiqui,
  • Saikh Mohammad Wabaidur,
  • Qazi Inamur Rahman,
  • Mohammad Kalim Ahmad Khan,
  • Salman Akhtar

摘要

Salmonella bacteria cause an infection called salmonellosis. Nontyphoidal salmonellae (NTS) are significant contributors to foodborne infections that must be reported. Infections caused by NTS affects both the blood stream and other sites that are free from bacteria and can lead to severe and potentially fatal invasive diseases. Ceftriaxone is a third-generation cephalosporin antibiotic used to treat bacterial infections like NTS. The antimicrobial properties of ceftriaxone stem from its capacity to hinder cell wall formation by interacting with penicillin-binding proteins (PBPs). The therapeutic issue lies in the resistance of NTS to ceftriaxone, thereby increasing the need for innovative antimicrobial medications. The primary goal of this research is to identify previously unknown ceftriaxone derivatives that could potentially serve as effective treatments for NTS, while also exhibiting a favorable pharmacokinetic profile. Retrieval of the target protein PBP was done from the Protein databank, and the 3D chemical structures were accessed through the PubChem database. The Lipinski rule of five and ADME prediction using Biovia Discovery Studio were employed to evaluate ceftriaxone and its similar structures. Extended analysis was completed by utilizing molecular dynamics simulation (MDS) studies and metabolic reactivity prediction via Xenosite server. In the docking study, it was shown that PL-1 and PL-2 possess inhibitory potential against PBP, with libdock scores of 126.6 and 124.10, respectively, higher than the control drug ceftriaxone's score of 95.4. The MDS molecular dynamics simulations demonstrated that the PL-1 complex with PBP exhibited similar stability when compared to the control ceftriaxone complex, showing average RMSD values of 10 Å and 10.5 Å, respectively. This outcome implies that PL-1 deserves additional scrutiny in the field of research. By considering the inhibitory effects of compound PL-1, it is plausible to conclude that the identified lead may exhibit an outstanding capacity to combat microbial pathogens.