ReviewFrontiers in microbiology2026
A review of research progress on periplasmic adaptor proteins in bacterial tripartite pumps.
Review in Frontiers in microbiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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0 citing papers in PubMed.
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gram-negative bacteria exhibit higher intrinsic resistance to antimicrobial agents than Gram-positive bacteria, largely attributable to their efficient multidrug efflux pumps. Among these, tripartite pumps spanning the inner membrane, periplasm, and outer membrane are central to both intrinsic and acquired resistance. Periplasmic adaptor proteins (PAPs) serve as the core connectors of these systems. Once regarded merely as passive scaffolds, PAPs are now confirmed to function as dynamic allosteric couplers that mediate complex assembly and conformational coordination. Moving beyond structural descriptions, this review synthesizes recent advances regarding the structural architecture of PAPs across RND (Resistance-Nodulation-Division), MFS (Major Facilitator Superfamily), and ABC (ATP-Binding Cassette) superfamilies, highlighting their conserved domains and subtype-specific adaptations. We place special emphasis on the multifaceted roles of PAPs-from substrate recognition and environmental sensing to their surprising function as extracellular "public goods" in bacterial necrosignaling. Furthermore, we dissect the clinical epidemiology of PAP overexpression and evaluate the potential of targeting PAPs with novel inhibitors. By reframing PAPs as active regulatory hubs rather than static linkers, this review elucidates the assembly logic of tripartite efflux mechanisms and provides a theoretical basis for combating antimicrobial resistance.
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