Secretin-interacting plug proteins prevent antibiotic influx during type IV pilus assembly in Pseudomonas aeruginosa

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. The assembly of type IV pili in Gram-negative bacteria involves the formation of secretin channels in the outer membrane. Here, the authors identify two periplasmic proteins that seal the secretin channel during pilus assembly, thus preventing loss of the outer-membrane permeability barrier.

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Publication Details

Journal
Nature Communications
Published
2026-05-29
DOI
https://doi.org/10.1038/s41467-026-73864-w
Primary Topic
Bacterial Genetics and Biotechnology
Type
article
Field-Weighted Citation Impact
0.00

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article

Secretin-interacting plug proteins prevent antibiotic influx during type IV pilus assembly in Pseudomonas aeruginosa

You‐Hee Cho, Jeong Min Chung, Frédéric Lauber, Bumhan Ryu et al.
Nature Communications
Bacterial Genetics and Biotechnology
article

Secretin-interacting plug proteins prevent antibiotic influx during type IV pilus assembly in Pseudomonas aeruginosa

You‐Hee Cho, Jeong Min Chung, Frédéric Lauber, Bumhan Ryu, Donghui Choe, Bi-o Kim, Melanie D. Ohi, Joel W. Sher, Youngki Yoo, Jean‐François Collet, Hongbaek Cho, Oh Hyun Kwon, Thomas G. Bernhardt, Sohee Park, Seung-Hyun Cho, Yeseul Lee
article en

Abstract

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. The assembly of type IV pili in Gram-negative bacteria involves the formation of secretin channels in the outer membrane. Here, the authors identify two periplasmic proteins that seal the secretin channel during pilus assembly, thus preventing loss of the outer-membrane permeability barrier.

Nature Communications
Howard Hughes Medical Institute (US), Harvard University (US), University of Michigan (US), Institute for Basic Science (KR), de Duve Institute (BE), Boston VA Research Institute (US), Korea Basic Science Institute (KR), Walloon Excellence in Lifesciences and Biotechnology (BE), CHA University (KR), Sungkyunkwan University (KR), Catholic University of Korea (KR)
National Research Foundation of Korea
Openalex Percentile: Top 6%
Bacterial Genetics and Biotechnology
DOIOpen Access PDFOpenAlex
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