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| Format: | Artículo científico |
| Langue: | en |
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PloS one
2026
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| Accès en ligne: | https://pubmed.ncbi.nlm.nih.gov/41544099/ |
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| _version_ | 1868266097721999360 |
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| author | Gopikrishnan, Mohanraj Doss C, George Priya |
| author_facet | Gopikrishnan, Mohanraj Doss C, George Priya Gopikrishnan, Mohanraj Doss C, George Priya |
| collection | PubMed - marine biology |
| contents | Integrative pan-resistome and transcriptomic characterization reveals differential gene expression signatures in carbapenem-resistant Acinetobacter baumannii: Insights into efflux pump regulation and therapeutic targeting strategies. Gopikrishnan, Mohanraj Doss C, George Priya Acinetobacter baumannii Carbapenems Anti-Bacterial Agents Transcriptome Microbial Sensitivity Tests Bacterial Proteins Gene Expression Profiling Gene Expression Regulation, Bacterial Drug Resistance, Multiple, Bacterial Acinetobacter Infections Acinetobacter baumannii is a significant, multidrug-resistant pathogen that is increasingly recognized as an agent associated with hospital infections. Its increasing resistance to carbapenems and other necessary antibiotics poses a serious threat to public health worldwide. The present study provides an integrative analysis of the pan-resistome and transcriptomic landscape of carbapenem-resistant A. baumannii (CRAB) under sub-minimum inhibitory concentrations (sub-MICs) of clinically relevant antibiotics, i.e., ciprofloxacin, amikacin sulfate, meropenem, and polymyxin B. A focused investigation was conducted into the transcriptional modulation of efflux transport systems and cellular stress-response mechanisms. To identify differentially expressed genes (DEGs) among the CRAB strains, parallel comparative RNA-Seq analysis with already available public datasets was undertaken. Concurrently, high-throughput virtual screening against the comprehensive marine natural product database (CMNPD) was done to identify inhibitors for MacB, a major ABC-type efflux transporter. Binding stability and interaction profiles of lead compounds were assessed via molecular dynamics simulations of 1000 ns. Transcriptomic profiling consistently showed increased levels of MacA-MacB efflux components, RcnB an intracellular stress-response protein LolA an outer membrane chaperone and surface antigen protein 1, especially under polymyxin B exposure. CMNPD27284 is the best candidate, having a strong binding affinity and stable interaction networks with critical MacB residues (-7.20 kcal/mol). These results highlight that efflux-mediated resistance and stress adaptation are crucial factors in CRAB, and they also indicate CMNPD27284 as a potential candidate for marine-derived scaffolding in developing drugs targeting the efflux pump. |
| format | Artículo científico |
| id | pubmed_41544099 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | PloS one |
| record_format | pubmed |
| spellingShingle | Integrative pan-resistome and transcriptomic characterization reveals differential gene expression signatures in carbapenem-resistant Acinetobacter baumannii: Insights into efflux pump regulation and therapeutic targeting strategies. Gopikrishnan, Mohanraj Doss C, George Priya Acinetobacter baumannii Carbapenems Anti-Bacterial Agents Transcriptome Microbial Sensitivity Tests Bacterial Proteins Gene Expression Profiling Gene Expression Regulation, Bacterial Drug Resistance, Multiple, Bacterial Acinetobacter Infections Integrative pan-resistome and transcriptomic characterization reveals differential gene expression signatures in carbapenem-resistant Acinetobacter baumannii: Insights into efflux pump regulation and therapeutic targeting strategies. Gopikrishnan, Mohanraj Doss C, George Priya Acinetobacter baumannii Carbapenems Anti-Bacterial Agents Transcriptome Microbial Sensitivity Tests Bacterial Proteins Gene Expression Profiling Gene Expression Regulation, Bacterial Drug Resistance, Multiple, Bacterial Acinetobacter Infections Acinetobacter baumannii is a significant, multidrug-resistant pathogen that is increasingly recognized as an agent associated with hospital infections. Its increasing resistance to carbapenems and other necessary antibiotics poses a serious threat to public health worldwide. The present study provides an integrative analysis of the pan-resistome and transcriptomic landscape of carbapenem-resistant A. baumannii (CRAB) under sub-minimum inhibitory concentrations (sub-MICs) of clinically relevant antibiotics, i.e., ciprofloxacin, amikacin sulfate, meropenem, and polymyxin B. A focused investigation was conducted into the transcriptional modulation of efflux transport systems and cellular stress-response mechanisms. To identify differentially expressed genes (DEGs) among the CRAB strains, parallel comparative RNA-Seq analysis with already available public datasets was undertaken. Concurrently, high-throughput virtual screening against the comprehensive marine natural product database (CMNPD) was done to identify inhibitors for MacB, a major ABC-type efflux transporter. Binding stability and interaction profiles of lead compounds were assessed via molecular dynamics simulations of 1000 ns. Transcriptomic profiling consistently showed increased levels of MacA-MacB efflux components, RcnB an intracellular stress-response protein LolA an outer membrane chaperone and surface antigen protein 1, especially under polymyxin B exposure. CMNPD27284 is the best candidate, having a strong binding affinity and stable interaction networks with critical MacB residues (-7.20 kcal/mol). These results highlight that efflux-mediated resistance and stress adaptation are crucial factors in CRAB, and they also indicate CMNPD27284 as a potential candidate for marine-derived scaffolding in developing drugs targeting the efflux pump. |
| title | Integrative pan-resistome and transcriptomic characterization reveals differential gene expression signatures in carbapenem-resistant Acinetobacter baumannii: Insights into efflux pump regulation and therapeutic targeting strategies. |
| topic | Acinetobacter baumannii Carbapenems Anti-Bacterial Agents Transcriptome Microbial Sensitivity Tests Bacterial Proteins Gene Expression Profiling Gene Expression Regulation, Bacterial Drug Resistance, Multiple, Bacterial Acinetobacter Infections |
| url | https://pubmed.ncbi.nlm.nih.gov/41544099/ |