The type IV pilin PilA couples surface attachment and cell-cycle initiation in Caulobacter crescentus
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Date
2020-04-28
Publication Type
Journal Article
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yes
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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.
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published
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Volume
117 (17)
Pages / Article No.
9546 - 9553
Publisher
National Academy of Sciences
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Date created
Subject
Caulobacter crescentus; c-di-GMP; type IV pilin; TnSeq; FRET microscopy
Organisational unit
09461 - Christen, Beat (ehemalig) / Christen, Beat (former)
Notes
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)
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)