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The RecA intein is a self-splicing protein element embedded within the RecA protein of Mycobacterium tuberculosis, the pathogen responsible for tuberculosis (Nature Communications, 2015). It acts as an intervening sequence that must be post-translationally removed through a process called protein splicing to generate a functional RecA enzyme (PNAS, 2015). RecA itself is a critical component of the bacterial DNA repair machinery and the SOS response, allowing the pathogen to survive DNA damage and oxidative stress within the host (UniProt, P9WGI7). Because inteins are not found in human proteins, the RecA intein represents a highly selective target for antimicrobial intervention (Journal of Biological Chemistry, 2016). Inhibition of this splicing process by small molecules or metal complexes prevents the maturation of RecA, thereby sensitizing the bacteria to existing antibiotics and host immune defenses (Applied Microbiology and Biotechnology, 2018). Compounds such as cisplatin and certain nucleoside analogs have been shown to effectively block the splicing mechanism, highlighting the potential for this target in treating multi-drug resistant tuberculosis (Angewandte Chemie, 2011).
Inhibition of the protein splicing mechanism of the RecA intein, which prevents the maturation of the RecA protein and disrupts DNA repair pathways in Mycobacterium tuberculosis (Nature Communications, 2015; Angewandte Chemie, 2011).
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