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Genome-Wide Investigation Reveals Potential Therapeutic Targets in Spp

Overview
Journal Biomed Res Int
Publisher Wiley
Date 2024 Apr 10
PMID 38595330
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Abstract

stands as a major contributor to bacterial dysentery worldwide , particularly in developing countries with inadequate sanitation and hygiene. The emergence of multidrug-resistant strains exacerbates the challenge of treating infections, particularly in regions where access to healthcare and alternative antibiotics is limited. Therefore, investigations on how bacteria evade antibiotics and eventually develop resistance could open new avenues for research to develop novel therapeutics. The aim of this study was to analyze whole genome sequence (WGS) of human pathogenic spp. to elucidate the antibiotic resistance genes (ARGs) and their mechanism of resistance, gene-drug interactions, protein-protein interactions, and functional pathways to screen potential therapeutic candidate(s). We comprehensively analyzed 45 WGS of , including ( = 17), ( = 14), ( = 11), and ( = 13), through different bioinformatics tools. Evolutionary phylogenetic analysis showed three distinct clades among the circulating strains of worldwide, with less genomic diversity. In this study, 2,146 ARGs were predicted in 45 genomes (average 47.69 ARGs/genome), of which only 91 ARGs were found to be shared across the genomes. Majority of these ARGs conferred their resistance through antibiotic efflux pump (51.0%) followed by antibiotic target alteration (23%) and antibiotic target replacement (18%). We identified 13 hub proteins, of which four proteins (e.g., tolC, acrR, mdtA, and gyrA) were detected as potential hub proteins to be associated with antibiotic efflux pump and target alteration mechanisms. These hub proteins were significantly ( < 0.05) enriched in biological process, molecular function, and cellular components. Therefore, the finding of this study suggests that human pathogenic strains harbored a wide range of ARGs that confer resistance through antibiotic efflux pumps and antibiotic target modification mechanisms, which must be taken into account to devise and formulate treatment strategy against this pathogen. Moreover, the identified hub proteins could be exploited to design and develop novel therapeutics against MDR pathogens like .

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References
1.
. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect Dis. 2018; 18(11):1211-1228. PMC: 6202444. DOI: 10.1016/S1473-3099(18)30362-1. View

2.
Puzari M, Sharma M, Chetia P . Emergence of antibiotic resistant Shigella species: A matter of concern. J Infect Public Health. 2017; 11(4):451-454. DOI: 10.1016/j.jiph.2017.09.025. View

3.
Baker S, Scott T . Antimicrobial-resistant Shigella: where do we go next?. Nat Rev Microbiol. 2023; 21(7):409-410. PMC: 10184058. DOI: 10.1038/s41579-023-00906-1. View

4.
Miryala S, Anbarasu A, Ramaiah S . Gene interaction network approach to elucidate the multidrug resistance mechanisms in the pathogenic bacterial strain Proteus mirabilis. J Cell Physiol. 2020; 236(1):468-479. DOI: 10.1002/jcp.29874. View

5.
Letunic I, Bork P . Interactive Tree Of Life (iTOL) v4: recent updates and new developments. Nucleic Acids Res. 2019; 47(W1):W256-W259. PMC: 6602468. DOI: 10.1093/nar/gkz239. View