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infection causes gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, and gastric cancer and can also promote thrombosis. It is estimated that approximately 4.5 billion individuals are infected, thus rendering the most prevalent microbial pathogen. Currently established regimes for antibiotic treatment are massively challenged by increasing drug resistance and the development of novel antimicrobial therapies is urgently required. The antibiotic capreomycin is clinically used against multiple drug-resistant strains of . It targets the complex between TlyA, a hemolysin- and RNA-binding protein, and the bacterial rRNA. In this study we have explored the possible antibacterial effects of capreomycin against several strains of and found only moderate activity which was comparable to metronidazole-resistant strains. Molecular docking of capreomycin to TlyA proteins from and identified several residues within TlyA which interact with the drug; however, binding affinities of - TlyA for capreomycin appear to be higher than those of - TlyA. The data suggest that capreomycin may warrant further investigations into its potential use as antibiotic against
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http://dx.doi.org/10.1155/2022/8924023 | DOI Listing |
Front Cell Infect Microbiol
August 2025
Institute of Tuberculosis Prevention and Control, Ningbo Municipal Center for Disease Control and Prevention, Ningbo, Zhejiang, China.
Rifampicin-resistant tuberculosis (RR-TB) remains a major global health challenge, with delayed sputum culture conversion (SCC) predicting poor treatment outcomes. This study integrated whole-genome sequencing (WGS) and machine learning to identify clinical and genomic determinants of SCC failure in 150 RR-TB patients (2019-2023). Phenotypic and genotypic analysis revealed high rates of isoniazid resistance (74.
View Article and Find Full Text PDFOrg Lett
August 2025
Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan.
Capreomycin (CMN) is a nonribosomal peptide (NRP) antituberculosis antibiotic. CMN biosynthesis involves a non-canonical -iterative adenylation (A) domain. Here, we report that the A domain-less nonribosomal peptide synthetase (NRPS) module CmnI utilizes another module's A domain CmnA-A to load the required amino acid onto its thiolation (T) domain.
View Article and Find Full Text PDFBMC Infect Dis
August 2025
Department of Clinical Laboratory, The Second Affiliated Hospital of Hainan Medical University, Haikou, 570311, People's Republic of China.
Objective: Multidrug-resistant tuberculosis (MDR-TB) remains a major public health challenge in China. Hainan, China's largest tropical island, possesses distinct socio-geographical features. However, the drug resistance patterns and molecular epidemiology of MDR-TB in this region have not been fully elucidated.
View Article and Find Full Text PDFNucleic Acids Res
July 2025
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, United States.
Loss of ribosomal RNA (rRNA) modifications incorporated by the intrinsic methyltransferase TlyA results in reduced sensitivity to tuberactinomycin antibiotics such as capreomycin. However, how rRNA methylation alters drug binding, particularly at the distant but functionally more important site in 23S rRNA helix 69 (H69), is currently unknown. We determined high-resolution cryo-electron microscopy structures of the Mycolicibacterium smegmatis 70S ribosome with or without the two ribose 2'-O-methyl modifications incorporated by TlyA.
View Article and Find Full Text PDFInt J Mycobacteriol
April 2025
Department of Biological Sciences, Faculty of Natural Sciences, Redeemer's University, Ede, Osun State, Nigeria.
Background: Tuberculosis (TB) remains a leading cause of mortality among people living with HIV/AIDS, who face a tenfold higher risk of Mycobacterium tuberculosis (MTB) infection. TB-HIV coinfection complicates disease management due to drug interactions, overlapping toxicities, immune reconstitution inflammatory syndrome, and high treatment burdens, potentially driving drug resistance. The emergence of resistant MTB further exacerbates this challenge.
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