Introducing ALZET?ew Model 2006 Pump Sign up for PNAS Online eTocs
Link: Info for AuthorsLink: Editorial BoardLink: AboutLink: SubscribeLink: AdvertiseLink: ContactLink: Sitemap Link: PNAS Home
Proceedings of the National Academy of Sciences
Link: Current Issue "" Link: Archives "" Link: Online Submission ""  Link: Advanced Search

Published online on January 22, 2004, 10.1073/pnas.0307694100
PNAS | February 3, 2004 | vol. 101 | no. 5 | 1339-1344


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supporting Figures
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via ISI Web of Science (57)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Déziel, E.
Right arrow Articles by Rahme, L. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Déziel, E.
Right arrow Articles by Rahme, L. G.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg  
What's this?

 Previous Article  | Table of Contents |  Next Article 

MICROBIOLOGY
Analysis of Pseudomonas aeruginosa 4-hydroxy-2-alkylquinolines (HAQs) reveals a role for 4-hydroxy-2-heptylquinoline in cell-to-cell communication

Eric Déziel *, François Lépine {dagger}, Sylvain Milot {dagger}, Jianxin He *, Michael N. Mindrinos {ddagger}, Ronald G. Tompkins *, and Laurence G. Rahme * §

*Department of Surgery, Harvard Medical School and Shriners Burns Institute, Massachusetts General Hospital, Boston, MA 02114; {dagger}Institut National de la Recherche Scientifique-Institut Armand-Frappier, Laval, Québec, QC, Canada H7V 1B7; and {ddagger}Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305

Communicated by Frederick M. Ausubel, Massachusetts General Hospital, Boston, MA, December 1, 2003 (received for review June 11, 2003)

Bacterial communities use "quorum sensing" (QS) to coordinate their population behavior through the action of extracellular signal molecules, such as the N-acyl-L-homoserine lactones (AHLs). The versatile and ubiquitous opportunistic pathogen Pseudomonas aeruginosa is a well-studied model for AHL-mediated QS. This species also produces an intercellular signal distinct from AHLs, 3,4-dihydroxy-2-heptylquinoline (PQS), which belongs to a family of poorly characterized 4-hydroxy-2-alkylquinolines (HAQs) previously identified for their antimicrobial activity. Here we use liquid chromatography (LC)/MS, genetics, and whole-genome expression to investigate the structure, biosynthesis, regulation, and activity of HAQs. We show that the pqsA-E operon encodes enzymes that catalyze the biosynthesis of five distinct classes of HAQs, and establish the sequence of synthesis of these compounds, which include potent cytochrome inhibitors and antibiotics active against human commensal and pathogenic bacteria. We find that anthranilic acid, the product of the PhnAB synthase, is the primary precursor of HAQs and that the HAQ congener 4-hydroxy-2-heptylquinoline (HHQ) is the direct precursor of the PQS signaling molecule. Significantly, whereas phnAB and pqsA-E are positively regulated by the virulence-associated transcription factor MvfR, which is also required for the expression of several QS-regulated genes, the conversion of HHQ to PQS is instead controlled by LasR. Finally, our results reveal that HHQ is itself both released from, and taken up by, bacterial cells where it is converted into PQS, suggesting that it functions as a messenger molecule in a cell-to-cell communication pathway. HAQ signaling represents a potential target for the pharmacological intervention of P. aeruginosa-mediated infections.

Abbreviations: QS, quorum sensing; AA, anthranilic acid; HAQ, 4-hydroxy-2-alkylquinolines; PQS, Pseudomonas quinolone signal (3,4-dihydroxy-2-heptylquinoline); HHQ, 4-hydroxy-2-heptylquinoline; HQNO, 4-hydroxy-2-heptylquinoline N-oxide; HNQ, 4-hydroxy-2-nonylquinoline; AHL, N-acyl-L-homoserine lactone; LC/MS, liquid chromatography/MS; CF, cystic fibrosis.

§ To whom correspondence should be addressed at: Wellman 340, Massachusetts General Hospital, 50 Blossom Street, Boston, MA 02114. E-mail: rahme{at}molbio.mgh.harvard.edu.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg    What's this?


This article has been cited by other articles in HighWire Press-hosted journals:


Home page
 J. Bacteriol.Home page
M. A. Oberhardt, J. Puchalka, K. E. Fryer, V. A. P. Martins dos Santos, and J. A. Papin
Genome-Scale Metabolic Network Analysis of the Opportunistic Pathogen Pseudomonas aeruginosa PAO1
J. Bacteriol., April 15, 2008; 190(8): 2790 - 2803.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
J. P. Coleman, L. L. Hudson, S. L. McKnight, J. M. Farrow III, M. W. Calfee, C. A. Lindsey, and E. C. Pesci
Pseudomonas aeruginosa PqsA Is an Anthranilate-Coenzyme A Ligase
J. Bacteriol., February 15, 2008; 190(4): 1247 - 1255.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
B. Baert, C. Baysse, S. Matthijs, and P. Cornelis
Multiple phenotypic alterations caused by a c-type cytochrome maturation ccmC gene mutation in Pseudomonas aeruginosa
Microbiology, January 1, 2008; 154(1): 127 - 138.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
S. M. Kirov, J. S. Webb, C. Y. O'May, D. W. Reid, J. K. K. Woo, S. A. Rice, and S. Kjelleberg
Biofilm differentiation and dispersal in mucoid Pseudomonas aeruginosa isolates from patients with cystic fibrosis
Microbiology, October 1, 2007; 153(10): 3264 - 3274.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
J. M. Farrow III and E. C. Pesci
Two Distinct Pathways Supply Anthranilate as a Precursor of the Pseudomonas Quinolone Signal
J. Bacteriol., May 1, 2007; 189(9): 3425 - 3433.
[Abstract] [Full Text] [PDF]

Home page
 Appl. Environ. Microbiol.Home page
J. Yao and A. M. Lambowitz
Gene Targeting in Gram-Negative Bacteria by Use of a Mobile Group II Intron ("Targetron") Expressed from a Broad-Host-Range Vector
Appl. Envir. Microbiol., April 15, 2007; 73(8): 2735 - 2743.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. R. Hoffman, E. Deziel, D. A. D'Argenio, F. Lepine, J. Emerson, S. McNamara, R. L. Gibson, B. W. Ramsey, and S. I. Miller
Selection for Staphylococcus aureus small-colony variants due to growth in the presence of Pseudomonas aeruginosa
PNAS, December 26, 2006; 103(52): 19890 - 19895.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
G. Xiao, J. He, and L. G. Rahme
Mutation analysis of the Pseudomonas aeruginosa mvfR and pqsABCDE gene promoters demonstrates complex quorum-sensing circuitry
Microbiology, June 1, 2006; 152(6): 1679 - 1686.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
C. F. Sio, L. G. Otten, R. H. Cool, S. P. Diggle, P. G. Braun, R. Bos, M. Daykin, M. Camara, P. Williams, and W. J. Quax
Quorum Quenching by an N-Acyl-Homoserine Lactone Acylase from Pseudomonas aeruginosa PAO1
Infect. Immun., March 1, 2006; 74(3): 1673 - 1682.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
A. Camilli and B. L. Bassler
Bacterial small-molecule signaling pathways.
Science, February 24, 2006; 311(5764): 1113 - 1116.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
K. L. Visick and C. Fuqua
Decoding Microbial Chatter: Cell-Cell Communication in Bacteria
J. Bacteriol., August 15, 2005; 187(16): 5507 - 5519.
[Full Text] [PDF]

Home page
 J. Bacteriol.Home page
K. L. Palmer, L. M. Mashburn, P. K. Singh, and M. Whiteley
Cystic Fibrosis Sputum Supports Growth and Cues Key Aspects of Pseudomonas aeruginosa Physiology
J. Bacteriol., August 1, 2005; 187(15): 5267 - 5277.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
C. Baysse, M. Cullinane, V. Denervaud, E. Burrowes, J. M. Dow, J. P. Morrissey, L. Tam, J. T. Trevors, and F. O'Gara
Modulation of quorum sensing in Pseudomonas aeruginosa through alteration of membrane properties
Microbiology, August 1, 2005; 151(8): 2529 - 2542.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
D. S. Wade, M. W. Calfee, E. R. Rocha, E. A. Ling, E. Engstrom, J. P. Coleman, and E. C. Pesci
Regulation of Pseudomonas Quinolone Signal Synthesis in Pseudomonas aeruginosa
J. Bacteriol., July 1, 2005; 187(13): 4372 - 4380.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
F. Bredenbruch, M. Nimtz, V. Wray, M. Morr, R. Muller, and S. Haussler
Biosynthetic Pathway of Pseudomonas aeruginosa 4-Hydroxy-2-Alkylquinolines
J. Bacteriol., June 1, 2005; 187(11): 3630 - 3635.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
S. Aendekerk, S. P. Diggle, Z. Song, N. Hoiby, P. Cornelis, P. Williams, and M. Camara
The MexGHI-OpmD multidrug efflux pump controls growth, antibiotic susceptibility and virulence in Pseudomonas aeruginosa via 4-quinolone-dependent cell-to-cell communication
Microbiology, April 1, 2005; 151(4): 1113 - 1125.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
L. M. Mashburn, A. M. Jett, D. R. Akins, and M. Whiteley
Staphylococcus aureus Serves as an Iron Source for Pseudomonas aeruginosa during In Vivo Coculture
J. Bacteriol., January 15, 2005; 187(2): 554 - 566.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
P. Cornelis and S. Aendekerk
A new regulator linking quorum sensing and iron uptake in Pseudomonas aeruginosa
Microbiology, April 1, 2004; 150(4): 752 - 756.
[Full Text] [PDF]