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Edited* by Frederick M. Ausubel, Harvard Medical School and Massachusetts General Hospital, Boston, MA, and approved June 23, 2014 (received for review February 25, 2014)
Significance
We have identified a phage-encoded protein that inhibits the bacterial ATPase PilB, which is involved in type IV pilus (TFP) biogenesis and function. This phage protein-mediated PilB dysfunction is regarded as the superinfection-exclusion maneuver of the phage toward TFP-specific phages. This study inspires an antipathogenic target based on the ATPases ubiquitously conserved in the motility and secretion machineries important in bacterial pathogenesis.
Abstract
Type IV pili (TFPs) are required for bacterial twitching motility and for phage infection in the opportunistic human pathogen Pseudomonas aeruginosa. Here we describe a phage-encoded protein, D3112 protein gp05 (hereafter referred to as Tip, representing twitching inhibitory protein), whose expression is necessary and sufficient to mediate the inhibition of twitching motility. Tip interacts with and blocks the activity of bacterial-encoded PilB, the TFP assembly/extension ATPase, at an internal 40-aa region unique to PilB. Tip expression results in the loss of surface piliation. Based on these observations and the fact that many P. aeruginosa phages require TFPs for infection, Tip-mediated twitching inhibition may represent a generalized strategy for superinfection exclusion. Moreover, because TFPs are required for full virulence, PilB may be an attractive target for the development of novel antiinfectives.
Footnotes
- ↵1To whom correspondence should be addressed. Email: youhee{at}cha.ac.kr.
Author contributions: Y.-H.C. designed research; I.-Y.C. performed research; H.-J.J. and H.-W.B. contributed new reagents/analytic tools; I.-Y.C. and Y.-H.C. analyzed data; and I.-Y.C. and Y.-H.C. wrote the paper.
The authors declare no conflict of interest.
↵*This Direct Submission article had a prearranged editor.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1403537111/-/DCSupplemental.
A phage protein inhibiting TFP assembly
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