Using Proteolytic Hypomorphs to Detect Small Molecule Mechanism of Action.
Methods Mol Biol
; 2314: 323-342, 2021.
Article
em En
| MEDLINE
| ID: mdl-34235661
ABSTRACT
With increasing prevalence of antimicrobial resistance, a fundamental goal of antibiotic discovery is to uncover new small molecules that prevent growth of pathogenic bacteria through diverse mechanisms of action. This goal is particularly pertinent for tuberculosis, caused by Mycobacterium tuberculosis. In this chapter, we describe the application of a chemical-genetic method, PROSPECT (primary screening of strains to prioritize expanded chemistry and targets), for sensitively detecting small molecule bioactivity using a pooled panel of hypomorphs (strains depleted in a particular essential gene) of M. tuberculosis. We describe statistical and heuristic approaches to assign small molecule mechanism of action from the resulting chemical-genetic interaction profiles.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
3_ND
Problema de saúde:
3_neglected_diseases
/
3_tuberculosis
Assunto principal:
Proteínas de Bactérias
/
Genes Essenciais
/
Bibliotecas de Moléculas Pequenas
/
Descoberta de Drogas
/
Mycobacterium tuberculosis
/
Antituberculosos
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Methods Mol Biol
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Reino Unido