Mutations in
Mycobacterium tuberculosis
drug resistance mechanisms
efflux pumps
molecular genetics
Journal
Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061
Informations de publication
Date de publication:
20 09 2022
20 09 2022
Historique:
pubmed:
4
8
2022
medline:
24
9
2022
entrez:
3
8
2022
Statut:
ppublish
Résumé
Tuberculosis (TB) is the leading cause of death from any bacterial infection, causing 1.5 million deaths worldwide each year. Due to the emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb) there have been significant efforts aimed at developing novel drugs to treat TB. One promising drug target in Mtb is the arabinogalactan biosynthetic enzyme DprE1, and there have been over a dozen unique chemical scaffolds identified which inhibit the activity of this protein. Among the most promising lead compounds are the benzothiazinones BTZ043 and PBTZ169, both of which are currently in or have completed phase IIa clinical trials. Due to the potential clinical utility of these drugs, we sought to identify potential synergistic interactions and new mechanisms of resistance using a genome-scale CRISPRi chemical-genetic screen with PBTZ169. We found that knockdown of
Identifiants
pubmed: 35920665
doi: 10.1128/aac.00904-22
pmc: PMC9487612
doi:
Substances chimiques
2-(2-methyl-1,4-dioxa-8-azaspiro(4.5)dec-8-yl)-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one
0
Antitubercular Agents
0
Diarylquinolines
0
Piperazines
0
Spiro Compounds
0
Thiazines
0
macozinone
A3M1353L40
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0090422Subventions
Organisme : NIAID NIH HHS
ID : U19 AI162584
Pays : United States
Organisme : NIAID NIH HHS
ID : DP2 AI144850
Pays : United States
Commentaires et corrections
Type : CommentIn
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