Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2016 May 24;113(21):6017-22. doi: 10.1073/pnas.1512947113. Epub 2016 May 9.

Type IV pilins regulate their own expression via direct intramembrane interactions with the sensor kinase PilS.

Author information

1
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8S 4K1; Michael G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, ON, Canada L8S 4K1.
2
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8S 4K1; Michael G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, ON, Canada L8S 4K1 burrowl@mcmaster.ca.

Abstract

Type IV pili are important virulence factors for many pathogens, including Pseudomonas aeruginosa Transcription of the major pilin gene-pilA-is controlled by the PilS-PilR two-component system in response to unknown signals. The absence of a periplasmic sensing domain suggested that PilS may sense an intramembrane signal, possibly PilA. We suggest that direct interactions between PilA and PilS in the inner membrane reduce pilA transcription when PilA levels are high. Overexpression in trans of PilA proteins with diverse and/or truncated C termini decreased native pilA transcription, suggesting that the highly conserved N terminus of PilA was the regulatory signal. Point mutations in PilA or PilS that disrupted their interaction prevented autoregulation of pilA transcription. A subset of PilA point mutants retained the ability to interact with PilS but could no longer decrease pilA transcription, suggesting that interaction between the pilin and sensor kinase is necessary but not sufficient for pilA autoregulation. Furthermore, PilS's phosphatase motif was required for the autoregulation of pilA transcription, suggesting that under conditions where PilA is abundant, the PilA-PilS interaction promotes PilR dephosphorylation and thus down-regulation of further pilA transcription. These data reveal a clever bacterial inventory control strategy in which the major subunit of an important P. aeruginosa virulence factor controls its own expression.

KEYWORDS:

Geobacter sulfurreducens; Pseudomonas aeruginosa; transcriptional regulation; two-component system; type IV pili

PMID:
27162347
PMCID:
PMC4889343
DOI:
10.1073/pnas.1512947113
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center