Blunted blades: new CRISPR-derived technologies to dissect microbial multi-drug resistance and biofilm formation

ABSTRACTThe spread of multi-drug-resistant (MDR) pathogens has rapidly outpaced the development of effective treatments. Diverse resistance mechanisms further limit the effectiveness of our best treatments, including multi-drug regimens and last line-of-defense antimicrobials. Biofilm formation is a...

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Main Authors: Christopher Gager, Ana L. Flores-Mireles
Format: Article
Language:English
Published: American Society for Microbiology 2024-04-01
Series:mSphere
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/msphere.00642-23
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author Christopher Gager
Ana L. Flores-Mireles
author_facet Christopher Gager
Ana L. Flores-Mireles
author_sort Christopher Gager
collection DOAJ
description ABSTRACTThe spread of multi-drug-resistant (MDR) pathogens has rapidly outpaced the development of effective treatments. Diverse resistance mechanisms further limit the effectiveness of our best treatments, including multi-drug regimens and last line-of-defense antimicrobials. Biofilm formation is a powerful component of microbial pathogenesis, providing a scaffold for efficient colonization and shielding against anti-microbials, which further complicates drug resistance studies. Early genetic knockout tools didn’t allow the study of essential genes, but clustered regularly interspaced palindromic repeat inference (CRISPRi) technologies have overcome this challenge via genetic silencing. These tools rapidly evolved to meet new demands and exploit native CRISPR systems. Modern tools range from the creation of massive CRISPRi libraries to tunable modulation of gene expression with CRISPR activation (CRISPRa). This review discusses the rapid expansion of CRISPRi/a-based technologies, their use in investigating MDR and biofilm formation, and how this drives further development of a potent tool to comprehensively examine multi-drug resistance.
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spelling doaj.art-2b43841f2e994c3da2b8b15fc98815cf2024-04-23T13:00:39ZengAmerican Society for MicrobiologymSphere2379-50422024-04-019410.1128/msphere.00642-23Blunted blades: new CRISPR-derived technologies to dissect microbial multi-drug resistance and biofilm formationChristopher Gager0Ana L. Flores-Mireles1Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USADepartment of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USAABSTRACTThe spread of multi-drug-resistant (MDR) pathogens has rapidly outpaced the development of effective treatments. Diverse resistance mechanisms further limit the effectiveness of our best treatments, including multi-drug regimens and last line-of-defense antimicrobials. Biofilm formation is a powerful component of microbial pathogenesis, providing a scaffold for efficient colonization and shielding against anti-microbials, which further complicates drug resistance studies. Early genetic knockout tools didn’t allow the study of essential genes, but clustered regularly interspaced palindromic repeat inference (CRISPRi) technologies have overcome this challenge via genetic silencing. These tools rapidly evolved to meet new demands and exploit native CRISPR systems. Modern tools range from the creation of massive CRISPRi libraries to tunable modulation of gene expression with CRISPR activation (CRISPRa). This review discusses the rapid expansion of CRISPRi/a-based technologies, their use in investigating MDR and biofilm formation, and how this drives further development of a potent tool to comprehensively examine multi-drug resistance.https://journals.asm.org/doi/10.1128/msphere.00642-23antimicrobialCRISPRifungibacteriamulti-drug resistancebiofilms
spellingShingle Christopher Gager
Ana L. Flores-Mireles
Blunted blades: new CRISPR-derived technologies to dissect microbial multi-drug resistance and biofilm formation
mSphere
antimicrobial
CRISPRi
fungi
bacteria
multi-drug resistance
biofilms
title Blunted blades: new CRISPR-derived technologies to dissect microbial multi-drug resistance and biofilm formation
title_full Blunted blades: new CRISPR-derived technologies to dissect microbial multi-drug resistance and biofilm formation
title_fullStr Blunted blades: new CRISPR-derived technologies to dissect microbial multi-drug resistance and biofilm formation
title_full_unstemmed Blunted blades: new CRISPR-derived technologies to dissect microbial multi-drug resistance and biofilm formation
title_short Blunted blades: new CRISPR-derived technologies to dissect microbial multi-drug resistance and biofilm formation
title_sort blunted blades new crispr derived technologies to dissect microbial multi drug resistance and biofilm formation
topic antimicrobial
CRISPRi
fungi
bacteria
multi-drug resistance
biofilms
url https://journals.asm.org/doi/10.1128/msphere.00642-23
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