Genome-Wide Investigation Reveals Potential Therapeutic Targets in Shigella spp.
Shigella stands as a major contributor to bacterial dysentery worldwide scale, particularly in developing countries with inadequate sanitation and hygiene. The emergence of multidrug-resistant strains exacerbates the challenge of treating Shigella infections, particularly in regions where access to...
| Publicado en: | BioMed Research International Vol. 2024; pp. 1 - 15 |
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| Autores principales: | , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
3/21/2024
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=176216132&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 176216132 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 3/21/2024 vid: 2024 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 176216132 176216132 176216132 10.1155/2024/5554208 176216132 ppf: 1 ppct: 14 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Genome-Wide Investigation Reveals Potential Therapeutic Targets in Shigella spp. aug: au: Hossain, Md. Arju Al Amin, Md. Khan, Md. Arif Refat, Md. Rashedur Rahman Sohel, Md Rahman, Md Habibur Islam, Ariful Hoque, M. Nazmul affil: Department of Biotechnology and Genetic Engineering, Mawlana Bhashani Science and Technology University, Tangail 1902, Bangladesh sug: subj: Genome Shigella Analysis Dysentery, Bacillary Drug Therapy Antibiotics Pharmacodynamics Shigella Drug Effects Drug Resistance, Microbial Pharmacogenetics Sequence Analysis Gene Expression Bacterial Proteins Analysis Bacterial Proteins Drug Effects Human Bioinformatics Phylogenetics Proteomics Descriptive Statistics T-Tests ab: Shigella stands as a major contributor to bacterial dysentery worldwide scale, particularly in developing countries with inadequate sanitation and hygiene. The emergence of multidrug-resistant strains exacerbates the challenge of treating Shigella 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 Shigella 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 Shigella, including S. flexneri (n = 17), S. dysenteriae (n = 14), S. boydii (n = 11), and S. sonnei (n = 13), through different bioinformatics tools. Evolutionary phylogenetic analysis showed three distinct clades among the circulating strains of Shigella 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 (p < 0.05) enriched in biological process, molecular function, and cellular components. Therefore, the finding of this study suggests that human pathogenic Shigella 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 Shigella. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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