The type IV pilin PilA couples surface attachment and cell-cycle initiation in Caulobacter crescentus.

Abstract

Understanding how bacteria colonize surfaces and regulate cell-cycle progression in response to cellular adhesion is of fundamental importance. Here, we use transposon sequencing in conjunction with fluorescence resonance energy transfer (FRET) microscopy to uncover the molecular mechanism for how surface sensing drives cell-cycle initiation in Caulobacter crescentus We identify the type IV pilin protein PilA as the primary signaling input that couples surface contact to cell-cycle initiation via the second messenger cyclic di-GMP (c-di-GMP). Upon retraction of pili filaments, the monomeric pilin reservoir in the inner membrane is sensed by the 17-amino acid transmembrane helix of PilA to activate the PleC-PleD two-component signaling system, increase cellular c-di-GMP levels, and signal the onset of the cell cycle. We termed the PilA signaling sequence CIP for "cell-cycle initiating pilin" peptide. Addition of the chemically synthesized CIP peptide initiates cell-cycle progression and simultaneously inhibits surface attachment. The broad conservation of the type IV pili and their importance in pathogens for host colonization suggests that CIP peptide mimetics offer strategies to inhibit surface sensing, prevent biofilm formation and control persistent infections.

• Authors: Luca Del Medico, Dario Cerletti, Philipp Schächle, Matthias Christen, Beat Christen
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 117 Issue 17 Pg. 9546-9553 (04 28 2020) ISSN: 1091-6490 [Electronic] United States
• PMID: 32295877 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 the Author(s). Published by PNAS.

Chemical References

• Fimbriae Proteins

Topics

• Bacterial Adhesion (physiology)
• Caulobacter crescentus (physiology)
• Cell Cycle (physiology)
• Fimbriae Proteins (genetics, metabolism)
• Gene Expression Regulation, Bacterial (physiology)