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.

c-di-GMP Homeostasis Is Critical for Heterocyst Development in Anabaena sp. PCC 7120

“…It was first discovered in Gluconacetobacter xylinus about 30years ago, as a positive allosteric regulator of cellulose synthase ( Ross et al, 1987 ). Subsequent studies have revealed that c-di-GMP regulates a variety of important cellular processes, including biofilm formation, motility, virulence, cell differentiation, cell cycle and mechanical sensing ( Tischler and Camilli, 2004 ; Kulesekara et al, 2006 ; Hengge, 2009 ; Boehm et al, 2010 ; Romling et al, 2013 ; Tschowri et al, 2014 ; Lori et al, 2015 ; Hug et al, 2017 ; Xu et al, 2019 ; Del Medico et al, 2020 ; Snyder et al, 2020 ). Such regulations may take place at the transcriptional, post-transcriptional, or post-translational levels by interacting with different types of effectors ( Romling et al, 2013 ; Chou and Galperin, 2016 ).…”

Regulation of the activity of the bacterial histidine kinase PleC by the scaffolding protein PodJ

“…One factor is that unphosphorylated DivK allosterically stimulates the kinase activity of PleC ( 26 ). Second, PleC signaling activity is regulated by pilus retraction upon surface contact ( 27 ). In this model, pilus retraction leads to the accumulation of PilA monomers in the periplasm that interacts and regulates PleC activity ( 27 ).…”

Environmental Conditions Modulate the Transcriptomic Response of Both Caulobacter crescentus Morphotypes to Cu Stress

“…However, a Cu stress-inducible aTSS was detected on its antisense strand. The PilA protein was recently shown to couple mechanical cell-surface contact with initiation of the cell cycle [ 122 ]. Expression of pilA is regulated by the cell-cycle regulator CtrA [ 123 ]; nonetheless, non-canonical factors governing its expression seem to be present.…”