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Systematic Identification of Cyclic-di-GMP Binding Proteins in Reveals a Novel Class of Cyclic-di-GMP-Binding ATPases Associated with Type II Secretion Systems


Cyclic-di-GMP (c-di-GMP) is a ubiquitous bacterial signaling molecule that regulates important bacterial functions, including virulence, antibiotic resistance, biofilm formation and cell division. The list of known c-di-GMP receptors is clearly incomplete. Here we utilized a systematic and unbiased biochemical approach to identify c-di-GMP receptors from the 3,812 genes of the Vibrio cholerae genome. Results from this analysis identified most known c-di-GMP receptors as well as MshE, a protein not known to interact with c-di-GMP. The c-di-GMP binding site was identified at the N-terminus of MshE and requires a conserved arginine residue in the 9th position. MshE is the ATPase that powers the secretion of the MshA pili onto the surface of the bacteria. We show that c-di-GMP binding to MshE is required for MshA export and the function of the pili in attachment and biofilm formation. ATPases responsible for related processes such as type IV pili and type II secretion were also tested for c-di-GMP binding, which identified the P. aeruginosa ATPase PA14_29490 as another c-di-GMP binding protein. These findings reveal a new class of c-di-GMP receptor and raise the possibility that c-di-GMP regulate membrane complexes through direct interaction with related type II secretion and type IV pili ATPases.


Vyšlo v časopise: Systematic Identification of Cyclic-di-GMP Binding Proteins in Reveals a Novel Class of Cyclic-di-GMP-Binding ATPases Associated with Type II Secretion Systems. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005232
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005232

Souhrn

Cyclic-di-GMP (c-di-GMP) is a ubiquitous bacterial signaling molecule that regulates important bacterial functions, including virulence, antibiotic resistance, biofilm formation and cell division. The list of known c-di-GMP receptors is clearly incomplete. Here we utilized a systematic and unbiased biochemical approach to identify c-di-GMP receptors from the 3,812 genes of the Vibrio cholerae genome. Results from this analysis identified most known c-di-GMP receptors as well as MshE, a protein not known to interact with c-di-GMP. The c-di-GMP binding site was identified at the N-terminus of MshE and requires a conserved arginine residue in the 9th position. MshE is the ATPase that powers the secretion of the MshA pili onto the surface of the bacteria. We show that c-di-GMP binding to MshE is required for MshA export and the function of the pili in attachment and biofilm formation. ATPases responsible for related processes such as type IV pili and type II secretion were also tested for c-di-GMP binding, which identified the P. aeruginosa ATPase PA14_29490 as another c-di-GMP binding protein. These findings reveal a new class of c-di-GMP receptor and raise the possibility that c-di-GMP regulate membrane complexes through direct interaction with related type II secretion and type IV pili ATPases.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


2015 Číslo 10
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