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Identification of Antibacterial Immunity Proteins in Escherichia coli using MALDI-TOF-TOF-MS/MS and Top-Down Proteomic Analysis
Published on: May 23, 2021
Unravelling Pasteurella multocida Toxin (PMT): Structural insights, antibiotic assessment, and identification of
Subodh Soni1, Priyanka2, Pooja Chugh1
1Centre for Medical Biotechnology, Maharshi Dayanand University, Rohtak, Haryana 124001, India.
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.
Insights
New antibiotics like Amikacin, Ertapenem, and Tigecycline show high efficacy against Pasteurella multocida toxin (PMT). This study identifies promising therapeutic agents to combat severe bacterial infections in veterinary and human medicine.
Area of Science:
- Microbiology
- Structural Biology
- Computational Chemistry
Background:
- Pasteurella multocida is a significant bacterial pathogen causing severe infections in various hosts.
- The Pasteurella multocida toxin (PMT) is a key virulence factor responsible for tissue damage and diseases like atrophic rhinitis.
Purpose of the Study:
- To investigate the structural basis of PMT.
- To identify potential antibiotic inhibitors against PMT using computational and experimental methods.
Main Methods:
- Experimental determination of wild and mutant-type PMT proteins.
- Computational virtual screening and molecular docking.
- Molecular dynamic simulations and MMPBSA analysis.
- Antibiotic Sensitivity Testing (AST) and disc diffusion tests.
Main Results:
- Amikacin, Ertapenem, and Tigecycline demonstrated superior efficacy against PMT.
- Disc diffusion tests validated the sensitivity and effectiveness of these antibiotics.
- The identified antibiotics showed greater efficacy compared to the standard drug.
Conclusions:
- Amikacin, Ertapenem, and Tigecycline are promising therapeutic agents against PMT.
- This research provides potential inhibitors for Pasteurella multocida infections.
- Findings address critical needs in veterinary and microbiological treatment strategies.
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