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Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis


Gram-negative pathogens depend on fibrous adhesive organelles to attach to target tissues and establish infection. The major class of these organelles is assembled via the classical, alternative and archaic chaperone-usher (CU) pathways. CU pathways are recognized as promising new targets for the next generation of antibacterial drugs. The recently discovered archaic and alternative systems are of particular interest, as they are implicated in biofilm formation of antibiotic resistant pathogens, have a wider phylogenetic distribution and are associated with a broader range of diseases than the classical systems. Here, we report an atomic-resolution insight into the structure and assembly mechanism of two such biofilm-forming organelles assembled via the archaic and alternative pathways. We show that the archaic and alternative systems are structurally related, but their assembly mechanism is strikingly different from the classical assembly pathway. Whereas the classical chaperones deliver folded subunits to the usher assembly platform, non-classical chaperones apply a unique binding mechanism to maintain subunits in substantially unfolded state. The open subunit core allows for a new mode of strand replacement during polymerisation, and also represents an attractive target for the rational design of antimicrobials.


Vyšlo v časopise: Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis. PLoS Pathog 11(11): e32767. doi:10.1371/journal.ppat.1005269
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005269

Souhrn

Gram-negative pathogens depend on fibrous adhesive organelles to attach to target tissues and establish infection. The major class of these organelles is assembled via the classical, alternative and archaic chaperone-usher (CU) pathways. CU pathways are recognized as promising new targets for the next generation of antibacterial drugs. The recently discovered archaic and alternative systems are of particular interest, as they are implicated in biofilm formation of antibiotic resistant pathogens, have a wider phylogenetic distribution and are associated with a broader range of diseases than the classical systems. Here, we report an atomic-resolution insight into the structure and assembly mechanism of two such biofilm-forming organelles assembled via the archaic and alternative pathways. We show that the archaic and alternative systems are structurally related, but their assembly mechanism is strikingly different from the classical assembly pathway. Whereas the classical chaperones deliver folded subunits to the usher assembly platform, non-classical chaperones apply a unique binding mechanism to maintain subunits in substantially unfolded state. The open subunit core allows for a new mode of strand replacement during polymerisation, and also represents an attractive target for the rational design of antimicrobials.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


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