Archives of Microbiology

, Volume 193, Issue 3, pp 227–234 | Cite as

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

Short Communication

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.

Keywords

Pseudomonas aeruginosa DesB Desaturase Virulence factor 

Notes

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).

References

  1. 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 174:3643–3649PubMedGoogle Scholar
  2. Beatson SA, Whitchurch CB, Semmler AB, Mattick JS (2002) Quorum sensing is not required for twitching motility in Pseudomonas aeruginosa. J Bacteriol 184:3598–3604CrossRefPubMedGoogle Scholar
  3. 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 177:7155–7163PubMedGoogle Scholar
  4. 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 104:5596–5601CrossRefPubMedGoogle Scholar
  5. 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 175:5934–5944PubMedGoogle Scholar
  6. Davey ME, Caiazza NC, O’Toole GA (2003) Rhamnolipid surfactant production affects biofilm architecture in Pseudomonas aeruginosa PAO1. J Bacteriol 185:1027–1036CrossRefPubMedGoogle Scholar
  7. 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 149:2005–2013CrossRefPubMedGoogle Scholar
  8. 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 172:884–900PubMedGoogle Scholar
  9. Heck LW, Morihara K, McRae WB, Miller EJ (1986) Specific cleavage of human type III and IV collagens by Pseudomonas aeruginosa elastase. Infect Immun 51:115–118PubMedGoogle Scholar
  10. Heck LW, Alarcon PG, Kulhavy RM, Morihara K, Russell MW, Mestecky JF (1990) Degradation of IgA proteins by Pseudomonas aeruginosa elastase. J Immunol 6:2253–2257Google Scholar
  11. Henrichsen J (1972) Bacterial surface translocation: A survey and a classification. Bacteriol Rev 36:478–503PubMedGoogle Scholar
  12. 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 179:5326–5332PubMedGoogle Scholar
  13. Holloway BW (1995) Genetic recombination in Pseudomonas aeruginosa. J Gen Microbiol 13:572–581Google Scholar
  14. 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 62:133–138CrossRefPubMedGoogle Scholar
  15. 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 33:924–929PubMedGoogle Scholar
  16. 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 182:5990–5996CrossRefPubMedGoogle Scholar
  17. 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 183:5213–5222CrossRefPubMedGoogle Scholar
  18. 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:R90CrossRefPubMedGoogle Scholar
  19. 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 27:1093–1099CrossRefPubMedGoogle Scholar
  20. 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 72:6836–6845CrossRefPubMedGoogle Scholar
  21. Liu PV (1974) Extracellular toxins of Pseudomonas aeruginosa. J Infect Dis 130:94–99Google Scholar
  22. 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 63–88Google Scholar
  23. 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 96:47–56CrossRefPubMedGoogle Scholar
  24. Mahajan-Miklos S, Tan M-W, Rahme LG, Ausubel FM (2000) Elucidating the molecular mechanisms of bacterial virulence using non-mammalian hosts. Mol Microbiol 37:981–988CrossRefPubMedGoogle Scholar
  25. 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 189:2164–2169CrossRefPubMedGoogle Scholar
  26. 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 190:2671–2679CrossRefPubMedGoogle Scholar
  27. 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 278:53123–53130CrossRefPubMedGoogle Scholar
  28. 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 73:5319–5328CrossRefPubMedGoogle Scholar
  29. Ran H, Hassett DJ, Lau GW (2003) Human targets of Pseudomonas aeruginosa pyocyanin. Proc Natl Acad Sci USA 100:14315–14320CrossRefPubMedGoogle Scholar
  30. Rashid MH, Kornberg A (2000) Inorganic polyphosphate is needed for swimming, swarming, and twitching motilities of Pseudomonas aeruginosa. Proc Natl Acad Sci USA 97:4885–4890CrossRefPubMedGoogle Scholar
  31. Sassetti CM, Rubin EJ (2003) Genetic requirements for mycobacterial survival during infection. Proc Natl Acad Sci USA 100:12989–12994CrossRefPubMedGoogle Scholar
  32. 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 83–109Google Scholar
  33. 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 62:1264–1277CrossRefPubMedGoogle Scholar
  34. Soberón-Chávez G, Lépine F, Déziel E (2005) Production of rhamnolipids by Pseudomonas aeruginosa. Appl Microbiol Biotechnol 68:718–725CrossRefPubMedGoogle Scholar
  35. Tamura Y, Suzuki S, Sawada T (1992) Role of elastase as a virulence factor in experimental Pseudomonas aeruginosa infection in mice. Microb Pathog 12:237–244CrossRefPubMedGoogle Scholar
  36. 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 96:715–720CrossRefPubMedGoogle Scholar
  37. 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 64:37–43PubMedGoogle Scholar
  38. 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 3–45Google Scholar
  39. Van Delden C, Iglewski BH (1998) Cell-to-cell signaling and Pseudomonas aeruginosa infections. Emerg Infect Dis 4:551–560CrossRefPubMedGoogle Scholar
  40. 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 55:1357–1378CrossRefPubMedGoogle Scholar
  41. Zhang YM, Zhu K, Frank MW, Rock CO (2007) A Pseudomonas aeruginosa transcriptional regulator which senses fatty acid structure. Mol Microbiol 66:622–632CrossRefPubMedGoogle Scholar
  42. 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 60:260–273CrossRefPubMedGoogle Scholar
  43. Zolfaghar I, Evans DJ, Fleiszig SM (2003) Twitching motility contributes to the role of pili in corneal infection caused by Pseudomonas aaeruginosa. Infect Immun 71:5389–5393CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Department of Microbiology, Immunology, and Pathology, IDRC at Foothills CampusColorado State UniversityFort CollinsUSA
  2. 2.Department of Oral Microbiology, College of DentistryWonkwang UniversityIksan, ChonbukSouth Korea

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