{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T09:19:05Z","timestamp":1782897545217,"version":"3.54.5"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:00:00Z","timestamp":1731628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Nowadays, the emergence of some microbial species resistant to antibiotics, both gram-positive and gram-negative bacteria, is due to changes in molecular activities, biological processes and their cellular structure in order to survive. The aim of the gene network analysis for the drug-resistant <jats:italic>Enterococcus faecium<\/jats:italic> as gram-positive and <jats:italic>Salmonella Typhimurium<\/jats:italic> as gram-negative bacteria was to gain insights into the important interactions between hub genes involved in key molecular pathways associated with cellular adaptations and the comparison of survival mechanisms of these two bacteria exposed to ciprofloxacin. To identify the gene clusters and hub genes, the gene networks in drug-resistant <jats:italic>E<\/jats:italic>. <jats:italic>faecium<\/jats:italic> and <jats:italic>S<\/jats:italic>. <jats:italic>Typhimurium<\/jats:italic> were analyzed using Cytoscape. Subsequently, the putative regulatory elements were found by examining the promoter regions of the hub genes and their gene ontology (GO) was determined. In addition, the interaction between milRNAs and up-regulated genes was predicted. <jats:italic>RcsC<\/jats:italic> and <jats:italic>D920_01853<\/jats:italic> have been identified as the most important of the hub genes in <jats:italic>S<\/jats:italic>. <jats:italic>Typhimurium<\/jats:italic> and <jats:italic>E<\/jats:italic>. <jats:italic>faecium<\/jats:italic>, respectively. The enrichment analysis of hub genes revealed the importance of efflux pumps, and different enzymatic and binding activities in both bacteria. However, <jats:italic>E<\/jats:italic>. <jats:italic>faecium<\/jats:italic> specifically increases phospholipid biosynthesis and isopentenyl diphosphate biosynthesis, whereas <jats:italic>S<\/jats:italic>. <jats:italic>Typhimurium<\/jats:italic> focuses on phosphorelay signal transduction, transcriptional regulation, and protein autophosphorylation. The similarities in the GO findings of the promoters suggest common pathways for survival and basic physiological functions of both bacteria, including peptidoglycan production, glucose transport and cellular homeostasis. The genes with the most interactions with milRNAs include <jats:italic>dpiB<\/jats:italic>, <jats:italic>rcsC<\/jats:italic> and <jats:italic>kdpD<\/jats:italic> in <jats:italic>S<\/jats:italic>. <jats:italic>Typhimurium<\/jats:italic> and <jats:italic>EFAU004_01228<\/jats:italic>, <jats:italic>EFAU004_02016<\/jats:italic> and <jats:italic>EFAU004_00870<\/jats:italic> in <jats:italic>E<\/jats:italic>. <jats:italic>faecium<\/jats:italic>, respectively. The results showed that gram-positive and gram-negative bacteria have different mechanisms to survive under antibiotic stress. By deciphering their intricate adaptations, we can develop more effective therapeutic approaches and combat the challenges posed by multidrug-resistant bacteria.<\/jats:p>","DOI":"10.1371\/journal.pone.0311434","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T18:32:33Z","timestamp":1731695553000},"page":"e0311434","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Comparison of the antibiotic resistance mechanisms in a gram-positive and a gram-negative bacterium by gene networks analysis"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0064-0265","authenticated-orcid":true,"given":"Nafiseh","family":"Davati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abozar","family":"Ghorbani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,11,15]]},"reference":[{"issue":"3","key":"pone.0311434.ref001","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1086\/318514","article-title":"Practice guidelines for the management of infectious diarrhea","volume":"32","author":"RL Guerrant","year":"2001","journal-title":"Clinical infectious diseases"},{"issue":"9","key":"pone.0311434.ref002","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a025320","article-title":"Topoisomerase inhibitors: fluoroquinolone mechanisms of action and resistance","volume":"6","author":"DC Hooper","year":"2016","journal-title":"Cold Spring Harbor perspectives in medicine"},{"issue":"10","key":"pone.0311434.ref003","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1093\/bioinformatics\/btx801","article-title":"Machine learning for classifying tuberculosis drug-resistance from DNA sequencing data","volume":"34","author":"Y Yang","year":"2018","journal-title":"Bioinformatics"},{"issue":"3","key":"pone.0311434.ref004","doi-asserted-by":"crossref","DOI":"10.1128\/CMR.00181-19","article-title":"Antimicrobial resistance in ESKAPE pathogens","volume":"33","author":"DM De Oliveira","year":"2020","journal-title":"Clinical microbiology reviews"},{"issue":"3","key":"pone.0311434.ref005","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1177\/0956462418799017","article-title":"Complete ciprofloxacin resistance in gonococcal isolates in an urban Ugandan clinic: findings from a cross-sectional study","volume":"30","author":"E Mabonga","year":"2019","journal-title":"International journal of STD & AIDS"},{"key":"pone.0311434.ref006","doi-asserted-by":"crossref","first-page":"1025633","DOI":"10.3389\/fpubh.2022.1025633","article-title":"The resistance mechanisms of bacteria against ciprofloxacin and new approaches for enhancing the efficacy of this antibiotic","volume":"10","author":"A Shariati","year":"2022","journal-title":"Frontiers in Public Health"},{"issue":"5","key":"pone.0311434.ref007","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.02763-16","article-title":"Subinhibitory concentrations of ciprofloxacin enhance antimicrobial resistance and pathogenicity of Enterococcus faecium","volume":"61","author":"C Sinel","year":"2017","journal-title":"Antimicrobial Agents and Chemotherapy"},{"issue":"4","key":"pone.0311434.ref008","doi-asserted-by":"crossref","first-page":"e0175234","DOI":"10.1371\/journal.pone.0175234","article-title":"RNA-seq-based analysis of drug-resistant Salmonella enterica serovar Typhimurium selected in vivo and in vitro","volume":"12","author":"L Li","year":"2017","journal-title":"PLoS One"},{"key":"pone.0311434.ref009","doi-asserted-by":"crossref","first-page":"373","DOI":"10.2165\/00003495-198835040-00003","article-title":"Ciprofloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use","volume":"35","author":"DM Campoli-Richards","year":"1988","journal-title":"Drugs"},{"key":"pone.0311434.ref010","unstructured":"Davati N. 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