Real-time evaluation of macozinone activity against Mycobacterium tuberculosis through bacterial nanomotion analysis.

Autor: Vocat A; Resistell AG, Muttenz, Switzerland.; Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Luraschi-Eggemann A; Resistell AG, Muttenz, Switzerland., Antoni C; Innovative Medicines for Tuberculosis (iM4TB), Lausanne, Switzerland., Cathomen G; Resistell AG, Muttenz, Switzerland., Cichocka D; Resistell AG, Muttenz, Switzerland., Greub G; Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.; Service of Infectious Diseases, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Riabova O; Research Centre of Biotechnology RAS, Leninsky Prospect, Moscow, Russia., Makarov V; Research Centre of Biotechnology RAS, Leninsky Prospect, Moscow, Russia., Opota O; Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Mendoza A; Innovative Medicines for Tuberculosis (iM4TB), Lausanne, Switzerland., Cole ST; Innovative Medicines for Tuberculosis (iM4TB), Lausanne, Switzerland., Sturm A; Resistell AG, Muttenz, Switzerland.
Jazyk: angličtina
Zdroj: Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2024 Nov 27, pp. e0131824. Date of Electronic Publication: 2024 Nov 27.
DOI: 10.1128/aac.01318-24
Abstrakt: Novel drugs and improved diagnostics for Mycobacterium tuberculosis (MTB) are urgently needed and go hand in hand. We evaluated the in vitro activity of two benzothiazinone drug candidates (MCZ, PBTZ169; BTZ043) and their main metabolites against MTB using advanced nanomotion technology. The results demonstrated significant reductions in MTB viability within 7 h, indicating the potential for rapid, precise antibiotic susceptibility testing based on a phenotypic read-out in real time. PBTZ169 and H 2 -PBTZ169 achieved 100% separation between the susceptible H37Rv and a resistant dprE1 mutant strain NTB1. These findings support nanomotion technology's potential for faster antibiotic susceptibility testing of novel MTB drug candidates targeting the DprE1 enzyme that could reduce empirical treatment duration and antibiotic resistance selection pressure due to inaccurate treatments.
Databáze: MEDLINE
Externí odkaz: