Aim: Amid the current global challenge of antimicrobial resistance, RNA polymerase remains a paramount therapeutic target for tuberculosis. Dual binding of rifampin (RIF) and a novel compound, DAAP1, demonstrated the suppression of RIF resistance. However, a paucity of data elucidating the structural mechanism of action of this synergistic interaction prevails. Methodology & results: Molecular dynamic simulations unraveled the synergistic inhibitory characteristics of DAAP1 and RIF. Co-binding induced a stable protein, increased the degree of compactness of binding site residues around RIF and subsequently an improved binding affinity toward RIF.
Conclusion: Findings established the structural mechanism by which DAAP1 stabilizes Mycobacterium tuberculosis RNA polymerase, thus possibly suppressing RIF resistance. This study will assist toward the design of novel inhibitors combating drug resistance in tuberculosis.
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http://dx.doi.org/10.4155/fmc-2017-0197 | DOI Listing |
Mycobacteriophages are viruses that specifically infect bacteria of the Mycobacterium genus. A substantial collection of mycobacteriophages has been isolated and characterized, offering valuable insights into their diversity and evolution. This collection also holds significant potential for therapeutic applications, particularly as an alternative to antibiotics in combating drug-resistant bacterial strains.
View Article and Find Full Text PDFmBio
January 2025
Department of Microbiology, UMass Chan Medical School, Worcester, Massachusetts, USA.
Unlabelled: (Mtb) exhibits an impressive ability to adapt to rapidly changing environments, despite its genome's apparent stability. Recently, phase variation through indel formation in homopolymeric tracts (HT) has emerged as a potentially important mechanism promoting adaptation in Mtb. This study examines the impact of common phase variants associated with the ESX-1 type VII secretion system, focusing on a highly variable HT upstream of the ESX-1 regulatory factor, .
View Article and Find Full Text PDFACS Infect Dis
January 2025
Infectious Diseases Division, CSIR─Indian Institute of Integrative Medicine, Jammu 180001, India.
Tuberculosis (TB), a leading infectious disease caused by the pathogen , poses a significant treatment challenge due to its unique characteristics and resistance to existing drugs. The conventional treatment regimens, which are lengthy and involve multiple drugs, often result in poor patient adherence and subsequent drug resistance, particularly with multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. This highlights the urgent need for novel anti-TB therapies and new drug targets.
View Article and Find Full Text PDFInfect Drug Resist
January 2025
Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
We present a rare case of asymptomatic allergic bronchopulmonary aspergillosis (ABPA) concurrent with active pulmonary tuberculosis. Allergic bronchopulmonary aspergillosis is an immunological pulmonary disorder characterized by hypersensitivity to Aspergillus fumigatus, while pulmonary tuberculosis (PTB) is a complex infection caused by Mycobacterium tuberculosis (MTB). The association between pulmonary tuberculosis infections and Aspergillus infections remains a fascinating area of inquiry.
View Article and Find Full Text PDFIn this work, we investigated individual bacteria belonging to strains of the Beijing family with different drug sensitivity (sensitive, multi and extensive drug-resistant) by surface-enhanced Raman spectroscopy (SERS) in the fingerprint region. The latter is focused on the spectral bands, which correspond to a set of glutathione bands and DNA methylation patterns revealed due to 5-methylcytosine spectral biomarkers. It is shown that these spectral features can be correlated with drug sensitivity and DNA methylation.
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