Targeting Gene Transcription Prevents Antibiotic Resistance
Innovative strategies are needed to curb the global health challenge of antibiotic resistance. The World Health Organization predicts that antibiotic resistance could lead to millions of deaths annually. Pharmaceutical experience has shown that modest alterations of commonly-used broad-spectrum anti...
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MDPI AG
2025-03-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/14/4/345 |
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| author | Paul F. Agris |
| author_facet | Paul F. Agris |
| author_sort | Paul F. Agris |
| collection | DOAJ |
| description | Innovative strategies are needed to curb the global health challenge of antibiotic resistance. The World Health Organization predicts that antibiotic resistance could lead to millions of deaths annually. Pharmaceutical experience has shown that modest alterations of commonly-used broad-spectrum antibiotics readily elicit resistant strains. Thus, continued simple iterative improvements on current antibiotics are not sustainable. Traditional strategies target single sites with the goal of a broad-spectrum antibiotic. In comparison, a novel strategy targets multiple sites in single- or multidrug-resistant Gram-positive bacterial pathogens. The objective is to exploit the mechanisms by which pathogenic bacteria require genes for transcriptional regulation. Transcription regulatory factors can be manipulated and their functions disrupted to hamper bacterial viability. Some transcription factors regulate one or more steps in metabolic pathways. Transcription factors are not always proteins; some are small-molecule metabolites triggering genetic functions through riboswitches, and others are RNAs. Novel agents have been discovered with computer-simulated docking to an unusual transcription regulatory site in nascent bacterial mRNA. These compounds exhibit innovative chemistries and modes of action that inhibit bacterial growth by binding to and blocking critical Gram-positive mRNA functions. The tRNA-dependent transcription regulation of amino acid metabolism illustrates the possibilities of novel strategies to inhibit antibiotic-resistant growth and thwart the emergence of novel resistant strains. |
| format | Article |
| id | doaj-art-905bac9a834f4e8eaf4e9613f33ccf49 |
| institution | OA Journals |
| issn | 2079-6382 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj-art-905bac9a834f4e8eaf4e9613f33ccf492025-08-20T02:28:40ZengMDPI AGAntibiotics2079-63822025-03-0114434510.3390/antibiotics14040345Targeting Gene Transcription Prevents Antibiotic ResistancePaul F. Agris0Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USAInnovative strategies are needed to curb the global health challenge of antibiotic resistance. The World Health Organization predicts that antibiotic resistance could lead to millions of deaths annually. Pharmaceutical experience has shown that modest alterations of commonly-used broad-spectrum antibiotics readily elicit resistant strains. Thus, continued simple iterative improvements on current antibiotics are not sustainable. Traditional strategies target single sites with the goal of a broad-spectrum antibiotic. In comparison, a novel strategy targets multiple sites in single- or multidrug-resistant Gram-positive bacterial pathogens. The objective is to exploit the mechanisms by which pathogenic bacteria require genes for transcriptional regulation. Transcription regulatory factors can be manipulated and their functions disrupted to hamper bacterial viability. Some transcription factors regulate one or more steps in metabolic pathways. Transcription factors are not always proteins; some are small-molecule metabolites triggering genetic functions through riboswitches, and others are RNAs. Novel agents have been discovered with computer-simulated docking to an unusual transcription regulatory site in nascent bacterial mRNA. These compounds exhibit innovative chemistries and modes of action that inhibit bacterial growth by binding to and blocking critical Gram-positive mRNA functions. The tRNA-dependent transcription regulation of amino acid metabolism illustrates the possibilities of novel strategies to inhibit antibiotic-resistant growth and thwart the emergence of novel resistant strains.https://www.mdpi.com/2079-6382/14/4/345antibiotic resistancediscovery strategynovel mRNA targetmulti-targeting |
| spellingShingle | Paul F. Agris Targeting Gene Transcription Prevents Antibiotic Resistance Antibiotics antibiotic resistance discovery strategy novel mRNA target multi-targeting |
| title | Targeting Gene Transcription Prevents Antibiotic Resistance |
| title_full | Targeting Gene Transcription Prevents Antibiotic Resistance |
| title_fullStr | Targeting Gene Transcription Prevents Antibiotic Resistance |
| title_full_unstemmed | Targeting Gene Transcription Prevents Antibiotic Resistance |
| title_short | Targeting Gene Transcription Prevents Antibiotic Resistance |
| title_sort | targeting gene transcription prevents antibiotic resistance |
| topic | antibiotic resistance discovery strategy novel mRNA target multi-targeting |
| url | https://www.mdpi.com/2079-6382/14/4/345 |
| work_keys_str_mv | AT paulfagris targetinggenetranscriptionpreventsantibioticresistance |