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

Natalia Kurepina; Liang Chen; Kaelea Composto; Dalin Rifat; Eric L. Nuermberger; Barry N. Kreiswirth

doi:10.1128/aac.00093-22

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

Natalia Kurepina, Liang Chen, Kaelea Composto, Dalin Rifat, Eric L. Nuermberger, Barry N. Kreiswirth

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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 b-lactam susceptibility. Our results showed that CRISPR inhibition of each gene led to a significant 3-log10 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.

Original language	English (US)
Journal	Antimicrobial agents and chemotherapy
Volume	66
Issue number	4
DOIs	https://doi.org/10.1128/aac.00093-22
State	Published - Apr 2022

Keywords

CRISPRi
Mycobacterium abscessus
b-lactam
peptidoglycan biosynthesis

ASJC Scopus subject areas

Pharmacology (medical)
Infectious Diseases
Pharmacology

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10.1128/aac.00093-22

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abstract = "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 b-lactam susceptibility. Our results showed that CRISPR inhibition of each gene led to a significant 3-log10 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.",

keywords = "CRISPRi, Mycobacterium abscessus, b-lactam, peptidoglycan biosynthesis",

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AU - Chen, Liang

AU - Composto, Kaelea

AU - Rifat, Dalin

AU - Nuermberger, Eric L.

AU - Kreiswirth, Barry N.

PY - 2022/4

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AB - 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 b-lactam susceptibility. Our results showed that CRISPR inhibition of each gene led to a significant 3-log10 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.

KW - CRISPRi

KW - Mycobacterium abscessus

KW - b-lactam

KW - peptidoglycan biosynthesis

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

Abstract

Keywords

ASJC Scopus subject areas

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