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Infectious Disease: Tuberculosis
Therapy: Chemotherapy
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Total 1398 results found since Jan 2013.
Host cell environments and antibiotic efficacy in tuberculosis
Trends Microbiol. 2023 Sep 12:S0966-842X(23)00253-6. doi: 10.1016/j.tim.2023.08.009. Online ahead of print.ABSTRACTThe aetiologic agent of tuberculosis (TB), Mycobacterium tuberculosis (Mtb), can survive, persist, and proliferate in a variety of heterogeneous subcellular compartments. Therefore, TB chemotherapy requires antibiotics crossing multiple biological membranes to reach distinct subcellular compartments and target these bacterial populations. These compartments are also dynamic, and our understanding of intracellular pharmacokinetics (PK) often represents a challenge for antitubercular drug development. In recent ...
Source: Trends in Microbiology - September 14, 2023 Category: Microbiology Authors: Nathan J Day Pierre Santucci Maximiliano G Gutierrez Source Type: research
Intricate link between siderophore secretion and drug efflux in < em > Mycobacterium tuberculosis < /em >
In this study, we show that M. tuberculosis mutants lacking components of the MmpS4-MmpL4 and MmpS5-MmpL5 systems are more susceptible to bedaquiline, clofazimine, and rifabutin, important drugs for treatment of drug-resistant TB. While genetic deletion experiments revealed similar functions of the MmpL4 and MmpL5 transporters in siderophore and drug secretion, complementation experiments indicated that the MmpS4-MmpL4 proteins alone are not sufficient to restore drug efflux in an M. tuberculosis mutant lacking both operons, in contrast to MmpS5-MmpL5. Importantly, an M. tuberculosis mutant lacking the recently discovered ...
Source: Antimicrobial Agents and Chemotherapy - September 7, 2023 Category: Microbiology Authors: Virginia Meikle Lei Zhang Michael Niederweis Source Type: research
Discovery and characterization of antimycobacterial nitro-containing compounds with distinct mechanisms of action and < em > in vivo < /em > efficacy
Antimicrob Agents Chemother. 2023 Aug 23:e0047423. doi: 10.1128/aac.00474-23. Online ahead of print.ABSTRACTNitro-containing compounds have emerged as important agents in the control of tuberculosis (TB). From a whole-cell high-throughput screen for Mycobacterium tuberculosis (Mtb) growth inhibitors, 10 nitro-containing compounds were prioritized for characterization and mechanism of action studies. HC2209, HC2210, and HC2211 are nitrofuran-based prodrugs that need the cofactor F420 machinery for activation. Unlike pretomanid which depends only on deazaflavin-dependent nitroreductase (Ddn), these nitrofurans depend on Ddn ...
Source: Antimicrobial Agents and Chemotherapy - August 23, 2023 Category: Microbiology Authors: Ifeanyichukwu E Eke John T Williams Elizabeth R Haiderer Veronica J Albrecht Heather M Murdoch Bassel J Abdalla Robert B Abramovitch Source Type: research
Lung microenvironments harbor < em > Mycobacterium tuberculosis < /em > phenotypes with distinct treatment responses
Antimicrob Agents Chemother. 2023 Aug 11:e0028423. doi: 10.1128/aac.00284-23. Online ahead of print.ABSTRACTTuberculosis lung lesions are complex and harbor heterogeneous microenvironments that influence antibiotic effectiveness. Major strides have been made recently in understanding drug pharmacokinetics in pulmonary lesions, but the bacterial phenotypes that arise under these conditions and their contribution to drug tolerance are poorly understood. A pharmacodynamic marker called the RS ratio® quantifies ongoing rRNA synthesis based on the abundance of newly synthesized precursor rRNA relative to mature structural rRNA...
Source: Antimicrobial Agents and Chemotherapy - August 11, 2023 Category: Microbiology Authors: Nicholas D Walter Jackie P Ernest Christian Dide-Agossou Allison A Bauman Michelle E Ramey Karen Rossmassler Lisa M Massoudi Samantha Pauly Reem Al Mubarak Martin I Voskuil Firat Kaya Jansy P Sarathy Matthew D Zimmerman V éronique Dartois Brendan K Podel Source Type: research
