Skip to main content

Advertisement

SpringerLink
Log in

Pseudomonas aeruginosa aerobic fatty acid desaturase DesB is important for virulence factor production

  • Short Communication
  • Published:
Archives of Microbiology Aims and scope Submit manuscript

Abstract

Unsaturated fatty acids (UFAs) play a pivotal role in maintaining a functional cellular membrane in response to changes in environmental factors. Unlike in other gram-negative bacteria, in Pseudomonas aeruginosa, UFA synthesis is governed by 2 pathways: (1) the anaerobic FabAB-mediated pathway and (2) the aerobic inducible DesA/DesB desaturase pathway. Although fatty acids are functional constituents of several known virulence factors, the roles of Pseudomonas aeruginosa fatty acid synthesis enzymes in virulence factor production and pathogenesis have not yet been examined. Previous studies have shown that the mycobacterial DesA1 and DesA3 proteins are required for full virulence. Therefore, we assessed the effect, if any, of mutations affecting the various UFA synthesis enzymes on virulence factor production. Testing of individual mutations or combinations of mutations revealed that desB mutants were severely deficient in the production of proteolytic enzymes, pyocyanin, and rhamnolipid. In addition, the desB mutants showed impaired swarming and twitching motilities and reduced virulence in the Caenorhabditis elegans infection model. Taken together, these results demonstrate that DesB is not only a fatty acid desaturase but also a factor required for full virulence in Pseudomonas aeruginosa. DesB may thus constitute a novel drug target.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  • Allen L, Dockrell DH, Pattery T, Lee DG, Cornelis P, Hellewell PG, Whyte MK (2005) Pyocyanin production by Pseudomonas aeruginosa induces neutrophil apoptosis and impairs neutrophil-mediated host defenses in vivo. J Immunol 174:3643–3649

    CAS  PubMed  Google Scholar 

  • Beatson SA, Whitchurch CB, Semmler AB, Mattick JS (2002) Quorum sensing is not required for twitching motility in Pseudomonas aeruginosa. J Bacteriol 184:3598–3604

    Article  CAS  PubMed  Google Scholar 

  • Brint JM, Ohman DE (1995) Synthesis of multiple exoproducts in Pseudomonas aeruginosa is under the control of RhlR-RhlI, another set of regulators in strain PAO1 with homology to the autoinducer-responsive LuxR-LuxI family. J Bacteriol 177:7155–7163

    CAS  PubMed  Google Scholar 

  • Brosch R, Gordon SV, Garnier T, Eiglmeier K, Frigui W, Valenti P, Dos Santos S, Duthoy S, Lacroix C, Garcia-Pelayo C, Inwald JK, Golby P, Garcia JN, Hewinson RG, Behr MA, Quail MA, Churcher C, Barrell BG, Parkhill J, Cole ST (2007) Genome plasticity of BCG and impact on vaccine efficacy. Proc Natl Acad Sci USA 104:5596–5601

    Article  CAS  PubMed  Google Scholar 

  • Darzins A (1993) The pilG gene product, required for Pseudomonas aeruginosa pilus production and twitching motility, is homologous to the enteric, single-domain response regulator CheY. J Bacteriol 175:5934–5944

    CAS  PubMed  Google Scholar 

  • Davey ME, Caiazza NC, O’Toole GA (2003) Rhamnolipid surfactant production affects biofilm architecture in Pseudomonas aeruginosa PAO1. J Bacteriol 185:1027–1036

    Article  CAS  PubMed  Google Scholar 

  • Déziel E, Lépine F, Milot S, Villemur R (2003) rhlA is required for the production of a novel biosurfactant promoting swarming motility in Pseudomonas aeruginosa: 3-(3-hydroxyalkanoyloxy)alkanoic acids (HAAs), the precursors of rhamnolipids. Microbiology 149:2005–2013

    Article  PubMed  Google Scholar 

  • Essar DW, Eberly L, Hadero A, Crawford IP (1990) Identification and characterization of genes for a second anthranilate synthase in Pseudomonas aeruginosa: interchangeability of the two anthranilate synthases and evolutionary implications. J Bacteriol 172:884–900

    CAS  PubMed  Google Scholar 

  • Heck LW, Morihara K, McRae WB, Miller EJ (1986) Specific cleavage of human type III and IV collagens by Pseudomonas aeruginosa elastase. Infect Immun 51:115–118

    CAS  PubMed  Google Scholar 

  • Heck LW, Alarcon PG, Kulhavy RM, Morihara K, Russell MW, Mestecky JF (1990) Degradation of IgA proteins by Pseudomonas aeruginosa elastase. J Immunol 6:2253–2257

    Google Scholar 

  • Henrichsen J (1972) Bacterial surface translocation: A survey and a classification. Bacteriol Rev 36:478–503

    CAS  PubMed  Google Scholar 

  • Hoang TT, Schweizer HP (1997) Fatty acid biosynthesis in Pseudomonas aeruginosa: cloning and characterization of the fabAB operon encoding beta-hydroxyacyl-acyl carrier protein dehydratase (FabA) and beta-ketoacyl-acyl carrier protein synthase I (FabB). J Bacteriol 179:5326–5332

    CAS  PubMed  Google Scholar 

  • Holloway BW (1995) Genetic recombination in Pseudomonas aeruginosa. J Gen Microbiol 13:572–581

    Google Scholar 

  • Hong Y, Ghebrehiwet B (1992) Effect of Pseudomonas aeruginosa elastase and alkaline protease on serum complement and isolated components C1q and C3. Clin Immunol Immunopathol 62:133–138

    Article  CAS  PubMed  Google Scholar 

  • Jaffar-Bandjee MC, Lazdunski A, Bally M, Carrere J, Chazalette JP, Galabert C (1995) Production of elastase, exotoxin A, and alkaline protease in sputa during pulmonary exacerbation of cystic fibrosis in patients chronically infected by Pseudomonas aeruginosa. J Clin Microbiol 33:924–929

    CAS  PubMed  Google Scholar 

  • Köhler T, Curty LK, Barja F, van Delden C, Pechère JC (2000) Swarming of Pseudomonas aeruginosa is dependent on cell-to-cell signaling and requires flagella and pili. J Bacteriol 182:5990–5996

    Article  PubMed  Google Scholar 

  • Köhler T, van Delden C, Curty LK, Hamzehpour MM, Pechere JC (2001) Overexpression of the MexEF-OprN multidrug efflux system affects cell-to-cell signaling in Pseudomonas aeruginosa. J Bacteriol 183:5213–5222

    Article  PubMed  Google Scholar 

  • Lee DG, Urbach JM, Wu G, Liberati NT, Feinbaum RL, Miyata S, Diggins LT, He J, Saucier M, Desiel E, Friedman L, Li L, Grills G, Montgomery K, Kucherlapati Pahme LG, Ausubel FM (2006) Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial. Genome Biol 7:R90

    Article  PubMed  Google Scholar 

  • Leone I, Chirillo MG, Raso T, Zucca M, Savoia D (2008) Phenotypic and genotypic characterization of Pseudomonas aeruginosa from cystic fibrosis patients. Eur J Clin Microbiol Infect Dis 27:1093–1099

    Article  CAS  PubMed  Google Scholar 

  • Liaw S-J, Lai H-C, Wang W-B (2004) Modulation of swarming and virulence by fatty acids through the RsbA protein Proteus mirabilis. Infect Immun 72:6836–6845

    Article  CAS  PubMed  Google Scholar 

  • Liu PV (1974) Extracellular toxins of Pseudomonas aeruginosa. J Infect Dis 130:94–99

    Google Scholar 

  • Liu PV (1979) Toxins of Pseudomonas aeruginosa. Pseudomonas aeruginosa. In: Doggett RG (ed) Clinical manifestations of infection and current therapy. Academic Press, New York, pp 63–88

    Google Scholar 

  • Mahajan-Miklos S, Tan M-W, Rahme LG, Ausubel FM (1999) Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa-Caenorhabditis elegans pathogenesis model. Cell 96:47–56

    Article  CAS  PubMed  Google Scholar 

  • Mahajan-Miklos S, Tan M-W, Rahme LG, Ausubel FM (2000) Elucidating the molecular mechanisms of bacterial virulence using non-mammalian hosts. Mol Microbiol 37:981–988

    Article  CAS  PubMed  Google Scholar 

  • Overhage J, Lewenza S, Marr AK, Hancock REW (2007) Identification of genes involved in swarming motility using a Pseudomonas aeruginosa PAO1 mini-Tn5-lux mutant library. J Bacteriol 189:2164–2169

    Article  CAS  PubMed  Google Scholar 

  • Overhage J, Bains M, Brazas MD, Hancock REW (2008) Swarming of Pseudomonas aeruginosa is a complex adaptation leading to increased production of virulence factors and antibiotic resistance. J Bacteriol 190:2671–2679

    Article  CAS  PubMed  Google Scholar 

  • Phetsuksiri B, Jackson M, Scherman H, McNeil M, Besra GS, Baulard AR, Slayden RA, DeBarber AE, Barry CE 3rd, Baird MS, Crick DC, Brennan PJ (2003) Unique mechanism of action of the thiourea drug isoxyl on Mycobacterium tuberculosis. J Biol Chem 278:53123–53130

    Article  CAS  PubMed  Google Scholar 

  • Prithiviraj B, Bais HP, Weir T, Suresh B, Najarro EH, Dayakar BV, Schweizer HP, Vivanco JM (2005) Down regulation of virulence factors of Pseudomonas aeruginosa by salicylic acid attenuates its virulence on Arabidopsis thaliana and Caenorhabditis elegans. Infect Immun 73:5319–5328

    Article  CAS  PubMed  Google Scholar 

  • Ran H, Hassett DJ, Lau GW (2003) Human targets of Pseudomonas aeruginosa pyocyanin. Proc Natl Acad Sci USA 100:14315–14320

    Article  CAS  PubMed  Google Scholar 

  • Rashid MH, Kornberg A (2000) Inorganic polyphosphate is needed for swimming, swarming, and twitching motilities of Pseudomonas aeruginosa. Proc Natl Acad Sci USA 97:4885–4890

    Article  CAS  PubMed  Google Scholar 

  • Sassetti CM, Rubin EJ (2003) Genetic requirements for mycobacterial survival during infection. Proc Natl Acad Sci USA 100:12989–12994

    Article  CAS  PubMed  Google Scholar 

  • Schweizer HP (2004) Fatty acid biosynthesis and biologically significant acyl transfer reactions in pseudomonads. In: Ramos J-L (ed) Pseudomonas, Vol. 3 biosynthesis of macromolecules and molecular metabolism. Kluwer Academic/Plenum Publishers, New York, pp 83–109

    Google Scholar 

  • Shrout JD, Chopp DL, Just CL, Hentzer M, Givskov M, Parsek MR (2006) The impact of quorum sensing and swarming motility on Pseudomonas aeruginosa biofilm formation is nutritionally conditional. Mol Microbiol 62:1264–1277

    Article  CAS  PubMed  Google Scholar 

  • Soberón-Chávez G, Lépine F, Déziel E (2005) Production of rhamnolipids by Pseudomonas aeruginosa. Appl Microbiol Biotechnol 68:718–725

    Article  PubMed  Google Scholar 

  • Tamura Y, Suzuki S, Sawada T (1992) Role of elastase as a virulence factor in experimental Pseudomonas aeruginosa infection in mice. Microb Pathog 12:237–244

    Article  CAS  PubMed  Google Scholar 

  • Tan M-W, Mahajan-Miklos S, Ausubel FM (1999) Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. Proc Natl Acad Sci USA 96:715–720

    Article  CAS  PubMed  Google Scholar 

  • Tang HB, DiMango E, Bryan R, Gambello M, Iglewski BH, Goldberg JB, Prince A (1996) Contribution of specific Pseudomonas aeruginosa virulence factors to pathogenesis of pneumonia in a neonatal mouse model of infection. Infect Immun 64:37–43

    CAS  PubMed  Google Scholar 

  • Van Delden CV (2004) Virulence factors in Pseudomonas aeruginosa. In: Ramos J-L (ed) Pseudomonas: virulence and gene regulation. Vol. 2. Kluwer Academic/Plenum Publishers, New York, pp 3–45

    Google Scholar 

  • Van Delden C, Iglewski BH (1998) Cell-to-cell signaling and Pseudomonas aeruginosa infections. Emerg Infect Dis 4:551–560

    Article  PubMed  Google Scholar 

  • Whitchurch CB, Beatson SA, Comolli JC, Jakobsen T, Sargent JL, Bertrand JJ, West J, Klausen M, Waite LL, Kang PJ, Tolker-Nielsen T, Mattick JS, Engel JN (2005) Pseudomonas aeruginosa fimL regulates multiple virulence functions by intersecting with Vfr-modulated pathways. Mol Microbiol 55:1357–1378

    Article  CAS  PubMed  Google Scholar 

  • Zhang YM, Zhu K, Frank MW, Rock CO (2007) A Pseudomonas aeruginosa transcriptional regulator which senses fatty acid structure. Mol Microbiol 66:622–632

    Article  CAS  PubMed  Google Scholar 

  • Zhu K, Choi KH, Schweizer HP, Rock CO, Zhang YM (2006) Two aerobic pathways for the formation of unsaturated fatty acids in Pseudomonas aeruginosa. Mol Microbiol 60:260–273

    Article  CAS  PubMed  Google Scholar 

  • Zolfaghar I, Evans DJ, Fleiszig SM (2003) Twitching motility contributes to the role of pili in corneal infection caused by Pseudomonas aaeruginosa. Infect Immun 71:5389–5393

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0004068).

Author information

Authors and Affiliations

  1. Department of Microbiology, Immunology, and Pathology, IDRC at Foothills Campus, Colorado State University, Fort Collins, CO, 80523-2025, USA

    Herbert P. Schweizer

  2. Department of Oral Microbiology, College of Dentistry, Wonkwang University, Iksan, Chonbuk, 570-749, South Korea

    Kyoung-Hee Choi

Authors
  1. Herbert P. Schweizer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyoung-Hee Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kyoung-Hee Choi.

Additional information

Communicated by David Kelly.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schweizer, H.P., Choi, KH. Pseudomonas aeruginosa aerobic fatty acid desaturase DesB is important for virulence factor production. Arch Microbiol 193, 227–234 (2011). https://doi.org/10.1007/s00203-010-0665-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00203-010-0665-6

Keywords

Search

Navigation