Unravelling Pasteurella multocida Toxin (PMT): Structural insights, antibiotic assessment, and identification of potential inhibitors

Subodh Soni; Priyanka; Pooja Chugh; Nisha Ghanghas; Manjeet Chahar; Sanjay Kumar; Manish Kumar Gupta; Hari Mohan

doi:10.1016/j.compbiolchem.2025.108567

Unravelling Pasteurella multocida Toxin (PMT): Structural insights, antibiotic assessment, and identification of potential inhibitors

Comput Biol Chem. 2025 Jun 23:119:108567. doi: 10.1016/j.compbiolchem.2025.108567. Online ahead of print.

Authors

Subodh Soni¹, Priyanka², Pooja Chugh¹, Nisha Ghanghas³, Manjeet Chahar¹, Sanjay Kumar⁴, Manish Kumar Gupta⁵, Hari Mohan⁶

Affiliations

¹ Centre for Medical Biotechnology, Maharshi Dayanand University, Rohtak, Haryana 124001, India.
² Department of Microbiology, Maharshi Dayanand University, Rohtak, Haryana 124001, India.
³ Department of Botany, Maharshi Dayanand University, Rohtak, Haryana 124001, India.
⁴ Bioinformatics Centre, Biotech Park, Sector G, Jankipuram, Lucknow, Uttar Pradesh 226021, India.
⁵ Department of Biotechnology, Faculty of Science, Veer Bahadur Singh Purvanchal University, Jaunpur, Uttar Pradesh 222003, India. Electronic address: manish.kumar.gupta@gmail.com.
⁶ Centre for Medical Biotechnology, Maharshi Dayanand University, Rohtak, Haryana 124001, India. Electronic address: harimohan.cmbt@mdurohtak.ac.in.

PMID: 40580590
DOI: 10.1016/j.compbiolchem.2025.108567

Abstract

Pasteurella multocida, a potent gram-negative bacterial pathogen, employs an array of virulence factors, viz lipopolysaccharides, adhesins, capsule and the prominent Pasteurella multocida toxin (PMT), play a significant role in establishing severe infections across a broad host range from cattle, birds, animals and human. PMT, a pivotal dermonecrotic toxin, exhibits mitogenic properties, causing tissue damage and atrophic rhinitis in diverse animal hosts. In this study, we scrutinized the structural basis insight of PMT, exercising experimentally determined wild and mutant-type proteins. Amikacin, Ertapenem, Tigecycline, and Vancomycin are identified as promising antibiotics by utilizing a computational virtual screening and molecular docking approach. Further assessment through molecular dynamic simulations over 100 ns, MMPBSA analysis, Antibiotic Sensitivity Testing (AST), revealed the superior efficacy of Amikacin (31 mm), Ertapenem (46 mm), and Tigecycline (38 mm) against PMT. Validation through disc diffusion tests confirmed their sensitivity and is superior to the standard drug, suggesting potential therapeutic agents against PMT. Our findings not only highlight promising antibiotic candidates but also pave the way for identification of potential inhibitors against Pasteurella multocida infection, thereby addressing critical needs in both veterinary and microbiological domains.

Keywords: AST; Molecular Dynamic Simulations; Molecular docking; PMT; Pasteurella multocida.