PE-PGRS family protein PE_PGRS57 (PE_PGRS57)

PE-PGRS57 (Rv3514) is a surface-exposed protein found in the Mycobacterium tuberculosis complex and belongs to the large Proline-Glutamic acid/Polymorphic GC-rich Repetitive Sequence (PE-PGRS) family (Seo et al., 2022). The protein is characterized by a conserved N-terminal PE domain, which is essential for its translocation and localization to the mycobacterial cell wall, and a variable C-terminal PGRS domain consisting of numerous glycine-rich repeats (Virulence, 2020). PE-PGRS57 has recently emerged as a significant therapeutic target following the discovery of a novel class of antitubercular compounds known as PPs (methyl (S)-1-((3-alkoxy-6,7-dimethoxyphenanthren-9-yl)methyl)-5-oxopyrrolidine-2-carboxylate derivatives). These PP derivatives exert potent bactericidal activity against drug-sensitive, multi-drug resistant (MDR), and extensively drug-resistant (XDR) M. tuberculosis by selectively targeting PE-PGRS57 (PLOS Biology, 2022). Because this protein is unique to the M. tuberculosis complex and absent in most other bacterial species, targeting it offers high specificity and prevents disruption of the host's commensal microbiome (PharmaFocus Europe). Resistance to these novel agents is primarily driven by missense mutations in the PE-PGRS57 gene, validating its role as the primary target of action. Like other members of its family, PE-PGRS57 is thought to play a vital role in the pathogen's ability to evade or modulate host immunity and persist within host tissues during infection.

Other names

Rv3514PE-PGRS57PGRS57

Selective targeting and inhibition of the PE-PGRS57 protein by phenanthrene-based pyrrolidinedione (PP) derivatives, which disrupts essential bacterial functions or host-interaction mechanisms required for Mycobacterium tuberculosis viability (Seo et al., 2022).