AI Article Synopsis
- The rise of multi-drug-resistant tuberculosis (MDR-TB) has made it increasingly difficult to prevent and control the disease, prompting the need for new treatment options.
- A program has been initiated to identify new agents with a good safety profile, focusing on targeting the unique lipid components of Mycobacterium tuberculosis, particularly mycolic acid.
- Screening compounds that can inhibit the biosynthesis of mycolic acid, specifically through the main drug target InhA, is a key strategy in developing effective treatments against MDR-TB.
Article Abstract
The challenges in preventing and controlling tuberculosis are further complicated by the deadly rise of multi-drug-resistant tuberculosis (MDR-TB). Recognizing the seriousness of the situation, we initiated a program to screen new agents that would satisfy these unmet needs and have a favorable safety profile. Mycobacteria are well known for their lipid-rich properties. In Mycobacterium tuberculosis, mycolic acid in particular has been established the wall component related to the pathogenesis in the host. There are approximately 250 identified genes related to biosynthesis of the lipid turnover that contain InhA, the main target of isoniazid. Thus, the logical approach for developing a chemotherapy agent against tubercle bacilli included screening compounds that could inhibit the biosyntheses of mycolic acid and that had a novel chemical structure to ensure improved efficacy against MDR-TB. Some of the screening systems established for those purposes and some of the candidates are outlined.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2174/156802607780059727 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Targeting the Heart of Mycobacterium: Advances in Anti-Tubercular Agents Disrupting Cell Wall Biosynthesis.
Pharmaceuticals (Basel)
January 2025
School of Pharmacy, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.
infections continue to pose a significant global health challenge, particularly due to the rise of multidrug-resistant strains, random mycobacterial mutations, and the complications associated with short-term antibiotic regimens. Currently, five approved drugs target cell wall biosynthesis in . This review provides a comprehensive analysis of these drugs and their molecular mechanisms.
View Article and Find Full Text PDF[Engineering of CmpLs enhances L-glutamate production of ].
Sheng Wu Gong Cheng Xue Bao
January 2025
Key Laboratory of Engineering Biology for Low-Carbon Manufacturing, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
The efficient production of L-glutamate is dependent on the product's rapid efflux, hence researchers have recently concentrated on artificially modifying its transport system and cell membrane wall structure. Considering the unique composition and structure of the cell wall of , we investigated the effects of CmpLs on L-glutamate synthesis and transport in SCgGC7, a constitutive L-glutamate efflux strain. First, the knockout strains of CmpLs were constructed, and it was confirmed that the deletion of CmpL1 and CmpL4 significantly improved the performance of L-glutamate producers.
View Article and Find Full Text PDFTargeting InhA in drug-resistant Mycobacterium tuberculosis: potent antimycobacterial activity of diaryl ether dehydrozingerone derivatives.
Arch Microbiol
January 2025
Clinical Microbiology and PK-PD Division, CSIR-Indian Institute of Integrative Medicine, Sanatnagar, Srinagar, J&K, 190005, India.
Tuberculosis (TB) remains a major global threat, with 10 million new cases and 1.5 million deaths each year. In multidrug-resistant tuberculosis (MDR-TB), resistance is most commonly observed against isoniazid (INH) and rifampicin (RIF), the two frontline drugs.
View Article and Find Full Text PDFFour novel nontuberculous mycobacteria species: sp. nov., sp. nov., sp. nov. and sp. nov. revived from a historical Danish strain collection.
Int J Syst Evol Microbiol
January 2025
International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, Denmark.
Four novel nontuberculous mycobacteria were discovered from a historical strain collection at the International Reference Laboratory of Mycobacteriology at Statens Serum Institut in Copenhagen, Denmark. Phylogenetic analysis combining the 16S , internal transcribed spacer and 23S elements, as well as a single-copy core-gene (, , and ) analysis of these freeze-dried mycobacteria, clinically isolated from gastric lavage samples between 1948 and 1955, showed to be associated with type strains grouping within the Terra and Fortuitum-Vaccae clade. Phenotypic characteristics, biochemical properties and fatty acid and mycolic acid profiles supported the classification as novel strains.
View Article and Find Full Text PDFManipulation and Structural Activity of AcpM in .
Biochemistry
January 2025
Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
(Mtb) is a leading cause of death, with an escalating global occurrence of drug-resistant infections that are partially attributed to cell wall mycolic acids derived from type II fatty acid biosynthesis (FAS-II). Here, the central acyl carrier protein, AcpM, contributes to the regulation of complex and specific protein-protein interactions (PPIs), though the orchestration of these events remain largely unresolved due to unique features of AcpM. Limitations include complexities in generating modified AcpM in a single state.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!