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The persistence of makes it difficult to eradicate the associated infection from the host. The flexible nature of mycobacteria and their ability to adapt to adverse host conditions give rise to different drug-tolerant phenotypes. Granuloma formation restricts nutrient supply, limits oxygen availability and exposes bacteria to a low pH environment, resulting in non-replicating bacteria. These non-replicating mycobacteria, which need high doses and long exposure to anti-tubercular drugs, are the root cause of lengthy chemotherapy. Novel strategies, which are effective against non-replicating mycobacteria, need to be adopted to shorten tuberculosis treatment. This not only will reduce the treatment time but also will help prevent the emergence of multi-drug-resistant strains of mycobacteria.
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http://dx.doi.org/10.1099/jmm.0.001695 | DOI Listing |
Arch Microbiol
August 2025
Department of Microbial Drugs, Helmholtz Center for Infection Research, Braunschweig, Inhoffenstrasse 7, 38124, Braunschweig, Germany.
Fungi of the order Diaporthales are prolific sources of antimicrobial secondary metabolites. In this paper, we describe antimicrobial and antituberculosis anthraquinones (AQs) from Diaporthe perseae, an endophytic fungus isolated and identified from the endemic Philippine medicinal plant Uvaria alba (Annonaceae). Large-scale rice fermentation of D.
View Article and Find Full Text PDFFront Microbiol
August 2025
Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
Treatment of (MAB) infections is complicated by the lack of bactericidal antibiotics, the ability of MAB to persist in the hypoxic environment of granulomas and the intrinsic antibiotic resistance, which results in patient treatment with drug combinations for several months. Therefore, the search for new drugs/drug combinations is an urgent need. This review provides a comprehensive update on the activity in the lungs of MAB-infected mice of new and old bactericidal and bacteriostatic compounds, alone and in combination, which showed killing greater than or equal to clinically used antibiotics and combination components.
View Article and Find Full Text PDFBioorg Med Chem
November 2025
Department of Pharmaceutical Engg. & Tech, IIT-Banaras Hindu University, Varanasi, UP 221005, India. Electronic address:
Cytochrome bd (Cyt-bd) oxidase, a key enzyme in the Mtb respiratory chain, is particularly crucial for ATP synthesis when the primary cytochrome bc:aa (Cyt-bc:aa) complex is compromised. There are several reported inhibitors of the Cyt-bd oxidase, predominantly featuring quinoline and quinazoline scaffolds. This study explores benzothiazole amides as potential inhibitors of Cyt-bd oxidase for their ability to deplete ATP in the presence of the Cyt-bc:aa inhibitor Q203.
View Article and Find Full Text PDFACS Infect Dis
August 2025
Department of Microbiology, University of Washington, Seattle, Washington 98109, United States.
In (Mtb), persisters are genotypically drug-sensitive bacteria that nonetheless survive antibiotic treatment. Persisters contribute to prolonged TB treatment duration and relapse risk, highlighting the need for new therapeutic strategies to effectively eliminate these tolerant subpopulations. In this study, we screened 2,336 FDA-approved compounds to identify agents that enhance the sterilizing activity of standard anti-TB drugs and prevent the regrowth of persisters.
View Article and Find Full Text PDFAdv Respir Med
June 2025
Biological and Bio-Computational Lab, Department of Life Science, School of Basic Sciences and Research, Sharda University, Greater Noida 201310, UP, India.
Dormancy occurs when (Mtb) enters a non-replicating and metabolically inactive state in response to hostile environment. During this state, it is highly resistant to conventional antibiotics, which increase the urgency to develop new potential drugs against dormant bacilli. In view of this, the dormancy survival regulator (DosR) protein is thought to be an essential component that plays a key role in bacterial adaptation to dormancy during hypoxic conditions.
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