Aplicações do CRISPR-Cas na clivagem de genes de resistência para ressensibilização bacteriana a antibióticos
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Abstract
The horizontal transmission of resistance genes between bacteria and the spread of multidrug-resistant strains are progressively exceeding the effectiveness limits of antimicrobial therapies. Considered an urgent and global problem, the constant evolution of bacteria's adaptive mechanisms emphasizes the need for the development of new antimicrobials. In this context, the CRISPR-Cas system and its gene editing capacity have emerged as a promising strategy to restore bacterial sensitivity to antibiotics by selectively cleaving genetic sequences associated with resistance mechanisms located in plasmids and chromosomes. Therefore, this study analyzes the mechanisms and possibilities of CRISPR to restore bacterial susceptibility and control multidrug-resistant and systematizes recent experimental evidence regarding its use. The methodology consisted of a qualitative narrative literature review, with data collection from the Web of Science, PubMed, and EMBASE databases, including in vitro and in vivo experimental studies published between 2015 and 2025. The results indicate that the use of the CRISPR-based approaches, mainly associated with the Cas9 nuclease, demonstrate promising outcomes in thetargeted cleavage of resistance genes, resulting in partial or complete resensitization in the majority of the analyzed studies. However, this technology presents several challenges related to transport mechanisms, such as limitations in capacity, host range restrictions, and low efficiency of conjugation. Furthermore, the high number of mutations in resistance genes hinders the design of efficient sgRNA and highlights the need for further advances in the area, despite the great therapeutic potential of the CRISPR-Cas system.
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