CRISPR Inhibition of Essential Peptidoglycan Biosynthesis Genes in Mycobacterium abscessus and Its Impact on β-Lactam Susceptibility.

Autor: Kurepina N; Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA., Chen L; Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.; Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, New Jersey, USA., Composto K; Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA., Rifat D; The Center for Tuberculosis Research, Department of Medicine, Johns Hopkins Universitygrid.21107.35, Baltimore, Maryland, USA., Nuermberger EL; The Center for Tuberculosis Research, Department of Medicine, Johns Hopkins Universitygrid.21107.35, Baltimore, Maryland, USA., Kreiswirth BN; Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.; Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, New Jersey, USA.
Jazyk: angličtina
Zdroj: Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2022 Apr 19; Vol. 66 (4), pp. e0009322. Date of Electronic Publication: 2022 Mar 21.
DOI: 10.1128/aac.00093-22
Abstrakt: We utilized a CRISPR interference (CRISPRi) assay to control the gene expressions of two predicted essential peptidoglycan biosynthesis genes, pbpB and cwIM , in Mycobacterium abscessus and to evaluate their contribution to β-lactam susceptibility. Our results showed that CRISPR inhibition of each gene led to a significant 3-log 10 reduction in CFU in the presence of imipenem but not for cefoxitin. These results demonstrate that CRISPRi provides an experimental approach to study drug/target interactions in M. abscessus.
Databáze: MEDLINE