CRISPR-Cas. A Revolution in the Treatment and Study of ESKAPE Infections: Pre-Clinical Studies

Aledo, Manuel González de; González-Bardanca, Mónica; Blasco, Lucía; Pacios, Olga; Bleriot, Inés; Fernández-García, Laura; López, María; Fernández-Quejo, Melisa; Bou, Germán; Tomás, María

doi:10.20944/preprints202105.0598.v1

2021

DOI: 10.20944/preprints202105.0598.v1

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CRISPR-Cas. A Revolution in the Treatment and Study of ESKAPE Infections: Pre-Clinical Studies

Manuel González de Aledo¹,

Mónica González-Bardanca²,

Lucía Blasco³

et al.

Abstract: One of the biggest threats we face globally is the emergence of antimicrobial resistant (AMR) bacteria, which runs in parallel with a lack in the development of new antimicrobials. Among these AMR bacteria, pathogens belonging to the ESKAPE group can be highlighted (Enterococcus spp, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp) due to their profile of drug resistance and virulence. Therefore, innovative lines of treatment must be developed … Show more

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Cited by 4 publications

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Progress in Alternative Strategies to Combat Antimicrobial Resistance: Focus on Antibiotics

et al. 2022

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Antibiotic resistance, and, in a broader perspective, antimicrobial resistance (AMR), continues to evolve and spread beyond all boundaries. As a result, infectious diseases have become more challenging or even impossible to treat, leading to an increase in morbidity and mortality. Despite the failure of conventional, traditional antimicrobial therapy, in the past two decades, no novel class of antibiotics has been introduced. Consequently, several novel alternative strategies to combat these (multi-) drug-resistant infectious microorganisms have been identified. The purpose of this review is to gather and consider the strategies that are being applied or proposed as potential alternatives to traditional antibiotics. These strategies include combination therapy, techniques that target the enzymes or proteins responsible for antimicrobial resistance, resistant bacteria, drug delivery systems, physicochemical methods, and unconventional techniques, including the CRISPR-Cas system. These alternative strategies may have the potential to change the treatment of multi-drug-resistant pathogens in human clinical settings.

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Progress in Alternative Strategies to Combat Antimicrobial Resistance: Focus on Antibiotics

et al. 2022

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The Mechanism of Bacterial Resistance and Potential Bacteriostatic Strategies

Zhang

Cheng

2022

Antibiotics

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Bacterial drug resistance is rapidly developing as one of the greatest threats to human health. Bacteria will adopt corresponding strategies to crack the inhibitory effect of antibiotics according to the antibacterial mechanism of antibiotics, involving the mutation of drug target, secreting hydrolase, and discharging antibiotics out of cells through an efflux pump, etc. In recent years, bacteria are found to constantly evolve new resistance mechanisms to antibiotics, including target protective protein, changes in cell morphology, and so on, endowing them with multiple defense systems against antibiotics, leading to the emergence of multi-drug resistant (MDR) bacteria and the unavailability of drugs in clinics. Correspondingly, researchers attempt to uncover the mystery of bacterial resistance to develop more convenient and effective antibacterial strategies. Although traditional antibiotics still play a significant role in the treatment of diseases caused by sensitive pathogenic bacteria, they gradually lose efficacy in the MDR bacteria. Therefore, highly effective antibacterial compounds, such as phage therapy and CRISPER-Cas precision therapy, are gaining an increasing amount of attention, and are considered to be the treatments with the moist potential with regard to resistance against MDR in the future. In this review, nine identified drug resistance mechanisms are summarized, which enhance the retention rate of bacteria under the action of antibiotics and promote the distribution of drug-resistant bacteria (DRB) in the population. Afterwards, three kinds of potential antibacterial methods are introduced, in which new antibacterial compounds exhibit broad application prospects with different action mechanisms, the phage therapy has been successfully applied to infectious diseases caused by super bacteria, and the CRISPER-Cas precision therapy as a new technology can edit drug-resistant genes in pathogenic bacteria at the gene level, with high accuracy and flexibility. These antibacterial methods will provide more options for clinical treatment, and will greatly alleviate the current drug-resistant crisis.

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CRISPR-Based Gene Editing in Acinetobacter baumannii to Combat Antimicrobial Resistance

et al. 2023

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Antimicrobial resistance (AMR) poses a significant threat to the health, social, environment, and economic sectors on a global scale and requires serious attention to addressing this issue. Acinetobacter baumannii was given top priority among infectious bacteria because of its extensive resistance to nearly all antibiotic classes and treatment options. Carbapenem-resistant A. baumannii is classified as one of the critical-priority pathogens on the World Health Organization (WHO) priority list of antibiotic-resistant bacteria for effective drug development. Although available genetic manipulation approaches are successful in A. baumannii laboratory strains, they are limited when employed on newly acquired clinical strains since such strains have higher levels of AMR than those used to select them for genetic manipulation. Recently, the CRISPR-Cas (Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein) system has emerged as one of the most effective, efficient, and precise methods of genome editing and offers target-specific gene editing of AMR genes in a specific bacterial strain. CRISPR-based genome editing has been successfully applied in various bacterial strains to combat AMR; however, this strategy has not yet been extensively explored in A. baumannii. This review provides detailed insight into the progress, current scenario, and future potential of CRISPR-Cas usage for AMR-related gene manipulation in A. baumannii.

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CRISPR-Cas. A Revolution in the Treatment and Study of ESKAPE Infections: Pre-Clinical Studies

Cited by 4 publications

References 93 publications

Progress in Alternative Strategies to Combat Antimicrobial Resistance: Focus on Antibiotics

Progress in Alternative Strategies to Combat Antimicrobial Resistance: Focus on Antibiotics

The Mechanism of Bacterial Resistance and Potential Bacteriostatic Strategies

CRISPR-Based Gene Editing in Acinetobacter baumannii to Combat Antimicrobial Resistance

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