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

Open access
Date
2019-09-27Type
- Working Paper
ETH Bibliography
yes
Altmetrics
Abstract
Understanding how bacteria colonize surfaces and regulate cell cycle progression in response to cellular adhesion is of fundamental importance. Here, we used transposon sequencing in conjunction with FRET microscopy to uncover the molecular mechanism how surface sensing drives cell cycle initiation in Caulobacter crescentus. We identified the type IV pilin protein PilA as the primary signaling input that couples surface contact to cell cycle initiation via the second messenger 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 new strategies to inhibit surface-sensing, prevent biofilm formation and control persistent infections. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000393899Publication status
publishedExternal links
Journal / series
bioRxivPublisher
Cold Spring Harbor LaboratorySubject
cell cycle; Type IV pili biogenesis; TnSeq; surface sensingOrganisational unit
09461 - Christen, Beat (ehemalig) / Christen, Beat (former)
Funding
166476 - Global identification and characterization of essential genome features by random transposon mutagenesis (SNF)
184664 - Chemical synthesis rewriting of a bacterial genome (SNF)
177164 - Intermicrobial and host-microbial interactions that determine the trajectory of mammalian microbial colorization in early life (SNF)
More
Show all metadata
ETH Bibliography
yes
Altmetrics