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

Pharmacy

Hackensack Meridian Health
Johns Hopkins University
Hackensack Meridian School of Medicine

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

26 Scopus citations

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
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

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

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",

author = "Natalia Kurepina and Liang Chen and Kaelea Composto and Dalin Rifat and Nuermberger, \{Eric L.\} and Kreiswirth, \{Barry N.\}",

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AU - Kurepina, Natalia

AU - Chen, Liang

AU - Composto, Kaelea

AU - Rifat, Dalin

AU - Nuermberger, Eric L.

AU - Kreiswirth, Barry N.

PY - 2022/4

Y1 - 2022/4

N2 - 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.

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

UR - https://www.scopus.com/pages/publications/85128446851

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DO - 10.1128/aac.00093-22

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JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 4

ER -

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

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