Pseudomonas aeruginosa aerobic fatty acid desaturase DesB is important for virulence factor production
- 309 Downloads
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.
KeywordsPseudomonas aeruginosa DesB Desaturase Virulence factor
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).
- 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
- 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
- Holloway BW (1995) Genetic recombination in Pseudomonas aeruginosa. J Gen Microbiol 13:572–581Google 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 33:924–929PubMedGoogle 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:R90CrossRefPubMedGoogle Scholar
- Liu PV (1974) Extracellular toxins of Pseudomonas aeruginosa. J Infect Dis 130:94–99Google 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 63–88Google 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 73:5319–5328CrossRefPubMedGoogle 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 83–109Google 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 3–45Google 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 55:1357–1378CrossRefPubMedGoogle Scholar