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TitleSecretin-interacting plug proteins prevent antibiotic influx during type IV pilus assembly in Pseudomonas aeruginosa.
Journal, issue, pagesNat Commun, Year 2026
Publish dateMay 29, 2026
AuthorsOh Hyun Kwon / Yeseul Lee / Bumhan Ryu / Joel W Sher / Sohee Park / Frédéric Lauber / Bi-O Kim / Youngki Yoo / Seung-Hyun Cho / Donghui Choe / You-Hee Cho / Jean-François Collet / Melanie D Ohi / Thomas G Bernhardt / Jeong Min Chung / Hongbaek Cho /
PubMed AbstractType IV pili (T4P) are important virulence factors that mediate host attachment and other pathogenic functions. In Gram-negative bacteria, T4P are assembled from pilin subunits at the inner membrane ...Type IV pili (T4P) are important virulence factors that mediate host attachment and other pathogenic functions. In Gram-negative bacteria, T4P are assembled from pilin subunits at the inner membrane (IM) and extend through the outer membrane (OM) via secretin channels. Although essential for T4P function, secretin complexes can impair the OM permeability barrier, potentially allowing entry of toxic compounds. The mechanisms that prevent such influx remain poorly understood. Here, we identify SlkA and SlkB (PA5122 and PA5123) as periplasmic proteins that interact with the T4P secretin channel and block antibiotic influx. Our data indicate that these proteins function as physical plugs sealing the channel until the IM complex docks and pilus assembly begins. These findings demonstrate that Slk proteins and the IM complex function redundantly to maintain OM barrier integrity, and that their interaction with the secretin channel represents a promising target for antibiotic potentiation.
External linksNat Commun / PubMed:42215499
MethodsEM (single particle)
Resolution2.45 - 4.35 Å
Structure data

EMDB-66444: Pseudomonas aeruginosa (PAO1) Outer membrane PilQ (Secretin) in C1 symmetry
Method: EM (single particle) / Resolution: 4.35 Å

EMDB-66445: Pseudomonas aeruginosa (PAO1) Outer membrane PilQ (Secretin) with SlkB in C1 symmetry
Method: EM (single particle) / Resolution: 2.85 Å

EMDB-66446: Pseudomonas aeruginosa (PAO1) Outer membrane PilQ (Secretin) with SlkA in C1 symmetry
Method: EM (single particle) / Resolution: 3.06 Å

66447

9x0w

EMDB-66447, PDB-9x0w:
Pseudomonas aeruginosa (PAO1) Outer membrane PilQ (Secretin) in C14 symmetry
Method: EM (single particle) / Resolution: 3.02 Å

66448

9x0x

EMDB-66448, PDB-9x0x:
Pseudomonas aeruginosa (PAO1) Outer membrane PilQ (Secretin) with SlkB in C14 symmetry
Method: EM (single particle) / Resolution: 2.45 Å

66449

9x0y

EMDB-66449, PDB-9x0y:
Pseudomonas aeruginosa (PAO1) Outer membrane PilQ (Secretin) with SlkA in C14 symmetry
Method: EM (single particle) / Resolution: 2.68 Å

Chemicals

ChemComp-PTY:
PHOSPHATIDYLETHANOLAMINE / phospholipid*YM

Source
  • pseudomonas aeruginosa pao1 (bacteria)
KeywordsTRANSPORT PROTEIN / type IV pili / secretin / plug / outer membrane / permeability barrier / antibiotics / drug resistance

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