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Article

Identification of Therapeutic Targets in an Emerging Gastrointestinal Pathogen Campylobacter ureolyticus and Possible Intervention through Natural Products

1
PCMD, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
2
Jamil-ur-Rahman Center for Genome Research, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
3
HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
4
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia
5
Clinical Laboratory Science Department, College of Applied Medical Science, Shaqra University, Al-Quwayiyah 11961, Saudi Arabia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Dóra Kovács and Simone Carradori
Antibiotics 2022, 11(5), 680; https://doi.org/10.3390/antibiotics11050680
Received: 8 April 2022 / Revised: 9 May 2022 / Accepted: 16 May 2022 / Published: 18 May 2022
(This article belongs to the Special Issue Clinical Pharmacology and Pharmacy of Antimicrobial Agents)
Campylobacter ureolyticus is a Gram-negative, anaerobic, non-spore-forming bacteria that causes gastrointestinal infections. Being the most prevalent cause of bacterial enteritis globally, infection by this bacterium is linked with significant morbidity and mortality in children and immunocompromised patients. No information on pan-therapeutic drug targets for this species is available yet. In the current study, a pan-genome analysis was performed on 13 strains of C. ureolyticus to prioritize potent drug targets from the identified core genome. In total, 26 druggable proteins were identified using subtractive genomics. To the best of the authors’ knowledge, this is the first report on the mining of drug targets in C. ureolyticus. UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) was selected as a promiscuous pharmacological target for virtual screening of two bacterial-derived natural product libraries, i.e., postbiotics (n = 78) and streptomycin (n = 737) compounds. LpxC inhibitors from the ZINC database (n = 142 compounds) were also studied with reference to LpxC of C. ureolyticus. The top three docked compounds from each library (including ZINC26844580, ZINC13474902, ZINC13474878, Notoginsenoside St-4, Asiaticoside F, Paraherquamide E, Phytoene, Lycopene, and Sparsomycin) were selected based on their binding energies and validated using molecular dynamics simulations. To help identify potential risks associated with the selected compounds, ADMET profiling was also performed and most of the compounds were considered safe. Our findings may serve as baseline information for laboratory studies leading to the discovery of drugs for use against C. ureolyticus infections. View Full-Text
Keywords: pan-genome; Campylobacter ureolyticus; UDP-3-O-acyl-N-acetylglucosamine deacetylase; LpxC; campylobacteriosis pan-genome; Campylobacter ureolyticus; UDP-3-O-acyl-N-acetylglucosamine deacetylase; LpxC; campylobacteriosis
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MDPI and ACS Style

Khan, K.; Basharat, Z.; Jalal, K.; Mashraqi, M.M.; Alzamami, A.; Alshamrani, S.; Uddin, R. Identification of Therapeutic Targets in an Emerging Gastrointestinal Pathogen Campylobacter ureolyticus and Possible Intervention through Natural Products. Antibiotics 2022, 11, 680. https://doi.org/10.3390/antibiotics11050680

AMA Style

Khan K, Basharat Z, Jalal K, Mashraqi MM, Alzamami A, Alshamrani S, Uddin R. Identification of Therapeutic Targets in an Emerging Gastrointestinal Pathogen Campylobacter ureolyticus and Possible Intervention through Natural Products. Antibiotics. 2022; 11(5):680. https://doi.org/10.3390/antibiotics11050680

Chicago/Turabian Style

Khan, Kanwal, Zarrin Basharat, Khurshid Jalal, Mutaib M. Mashraqi, Ahmad Alzamami, Saleh Alshamrani, and Reaz Uddin. 2022. "Identification of Therapeutic Targets in an Emerging Gastrointestinal Pathogen Campylobacter ureolyticus and Possible Intervention through Natural Products" Antibiotics 11, no. 5: 680. https://doi.org/10.3390/antibiotics11050680

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