1887

Abstract

Gamma-aminobutyric acid (GABA) is widespread in the environment and can be used by animal and plants as a communication molecule. species, in particular fluorescent ones, synthesize GABA and express GABA-binding proteins. In this study, we investigated the effects of GABA on the virulence of . While exposure to GABA (10 µM) did not modify either the growth kinetics or the motility of the bacterium, its cytotoxicity and virulence were strongly increased. The ‘fast killing test’ model revealed that GABA acts essentially through an increase in diffusible toxin(s). GABA also modulates the biofilm formation activity and adhesion properties of PAO1. GABA has no effect on cell surface polarity, biosurfactant secretion or on the lipopolysaccharide structure. The production of several exo-enzymes, pyoverdin and exotoxin A is not modified by GABA but we observed an increase in cyanogenesis which, by itself, could explain the effect of GABA on virulence. This mechanism appears to be regulated by quorum sensing. A proteomic analysis revealed that the effect of GABA on cyanogenesis is correlated with a reduction of oxygen accessibility and an over-expression of oxygen-scavenging proteins. GABA also promotes specific changes in the expression of thermostable and unstable elongation factors Tuf/Ts involved in the interaction of the bacterium with the host proteins. Taken together, these results suggest that GABA is a physiological regulator of virulence.

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2013-02-01
2024-03-28
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References

  1. Aballay A., Ausubel F. M. ( 2002). Caenorhabditis elegans as a host for the study of host-pathogen interactions. Curr Opin Microbiol 5:97–101 [View Article][PubMed]
    [Google Scholar]
  2. Angulo M. C., Le Meur K., Kozlov A. S., Charpak S., Audinat E. ( 2008). GABA, a forgotten gliotransmitter. Prog Neurobiol 86:297–303 [View Article][PubMed]
    [Google Scholar]
  3. Barbey C., Crépin A., Cirou A., Budin-Verneuil A., Orange N., Feuilloley M., Faure D., Dessaux Y., Burini J.-F., Latour X. ( 2012). Catabolic pathway of gamma-caprolactone in the biocontrol agent Rhodococcus erythropolis . J Proteome Res 11:206–216 [View Article][PubMed]
    [Google Scholar]
  4. Bellon-Fontaine M. N., Rault J., Van Oss C. J. ( 1996). Microbial adhesion to solvents: a novel method to determine the electron-donor/electron-acceptor or Lewis acid-base properties of microbial cells. Colloids Surf B Biointerfaces 7:47–53 [View Article]
    [Google Scholar]
  5. Blier A.-S., Veron W., Bazire A., Gérault E., Taupin L., Vieillard J., Rehel K., Dufour A., Le Derf F. & other authors ( 2011). C-type natriuretic peptide modulates quorum sensing molecule and toxin production in Pseudomonas aeruginosa . Microbiology 157:1929–1944 [View Article][PubMed]
    [Google Scholar]
  6. Blier A. S., Vieillard J., Gerault E., Dagorn A., Varacavoudin T., Le Derf F., Orange N., Feuilloley M., Lesouhaitier O. ( 2012). Quantification of Pseudomonas aeruginosa hydrogen cyanide production by a polarographic approach. J Microbiol Methods 90:20–24 [View Article][PubMed]
    [Google Scholar]
  7. Bouché N., Lacombe B., Fromm H. ( 2003). GABA signaling: a conserved and ubiquitous mechanism. Trends Cell Biol 13:607–610 [View Article][PubMed]
    [Google Scholar]
  8. Brechtel C. E., King S. C. ( 1998). 4-Aminobutyrate (GABA) transporters from the amine-polyamine-choline superfamily: substrate sprcificity and ligand recognition profile of the 4-aminobutyrate permease from Bacillus subtilis.. Biochem J 333:565–571 [View Article][PubMed]
    [Google Scholar]
  9. Carrillo P. G., Mardaraz C., Pitta-Alvarez S. I., Giulietti A. M. ( 1996). Isolation and selection of biosurfactant-producing bacteria. J Microbiol Biotechnol 12:82–84 [View Article]
    [Google Scholar]
  10. Castric K. F., McDevitt D. A., Castric P. A. ( 1981). Influence of aeration on hydrogen cyanide biosynthesis by Pseudomonas aeruginosa . Curr Microbiol 5:223–226 [View Article]
    [Google Scholar]
  11. Chevrot R., Rosen R., Haudecoeur E., Cirou A., Shelp B. J., Ron E., Faure D. ( 2006). GABA controls the level of quorum-sensing signal in Agrobacterium tumefaciens . Proc Natl Acad Sci U S A 103:7460–7464 [View Article][PubMed]
    [Google Scholar]
  12. Chou H. T., Kwon D. H., Hegazy M., Lu C. D. ( 2008). Transcriptome analysis of agmatine and putrescine catabolism in Pseudomonas aeruginosa PAO1. J Bacteriol 190:1966–1975 [View Article][PubMed]
    [Google Scholar]
  13. Darveau R. P., Hancock R. E. ( 1983). Procedure for isolation of bacterial lipopolysaccharides from both smooth and rough Pseudomonas aeruginosa and Salmonella typhimurium strains. J Bacteriol 155:831–838[PubMed]
    [Google Scholar]
  14. de Bruijn I., de Kock M. J., Yang M., de Waard P., van Beek T. A., Raaijmakers J. M. ( 2007). Genome-based discovery, structure prediction and functional analysis of cyclic lipopeptide antibiotics in Pseudomonas species. Mol Microbiol 63:417–428 [View Article][PubMed]
    [Google Scholar]
  15. Déziel E., Lépine F., Milot S., Villemur R. ( 2000). Mass spectrometry monitoring of rhamnolipids from a growing culture of Pseudomonas aeruginosa strain 57RP. Biochim Biophys Acta 1485:145–152 [View Article][PubMed]
    [Google Scholar]
  16. Diggle S. P., Cornelis P., Williams P., Cámara M. ( 2006). 4-quinolone signalling in Pseudomonas aeruginosa: old molecules, new perspectives. Int J Med Microbiol 296:83–91 [View Article][PubMed]
    [Google Scholar]
  17. Duclairoir Poc C., Groboillot A., Lesouhaitier O., Morin J.-P., Orange N., Feuilloley M. J. ( 2011). Caenorhabditis elegans: a model to monitor bacterial air quality. BMC Res Notes 4:503 [View Article][PubMed]
    [Google Scholar]
  18. Fothergill J. L., Winstanley C., James C. E. ( 2012). Novel therapeutic strategies to counter Pseudomonas aeruginosa infections. Expert Rev Anti Infect Ther 10:219–235 [View Article][PubMed]
    [Google Scholar]
  19. Gaines J. M., Carty N. L., Colmer-Hamood J. A., Hamood A. N. ( 2005). Effect of static growth and different levels of environmental oxygen on toxA and ptxR expression in the Pseudomonas aeruginosa strain PAO1. Microbiology 151:2263–2275 [View Article][PubMed]
    [Google Scholar]
  20. Gallagher L. A., Manoil C. ( 2001). Pseudomonas aeruginosa PAO1 kills Caenorhabditis elegans by cyanide poisoning. J Bacteriol 183:6207–6214 [View Article][PubMed]
    [Google Scholar]
  21. Goure J., Pastor A., Faudry E., Chabert J., Dessen A., Attree I. ( 2004). The V antigen of Pseudomonas aeruginosa is required for assembly of the functional PopB/PopD translocation pore in host cell membranes. Infect Immun 72:4741–4750 [View Article][PubMed]
    [Google Scholar]
  22. Guthrie G. D., Nicholson-Guthrie C. S. ( 1989). gamma-Aminobutyric acid uptake by a bacterial system with neurotransmitter binding characteristics. Proc Natl Acad Sci U S A 86:7378–7381 [View Article][PubMed]
    [Google Scholar]
  23. Guthrie G. D., Nicholson-Guthrie C. S., Leary H. L. Jr ( 2000). A bacterial high-affinity GABA binding protein: isolation and characterization. Biochem Biophys Res Commun 268:65–68 [View Article][PubMed]
    [Google Scholar]
  24. Hiemenz P. C., Lagowski J. J. ( 1977). Principles of Colloid and Surface Chemistry209 New York: Marcel Dekker Ed;
    [Google Scholar]
  25. Higuchi T., Hayashi H., Abe K. ( 1997). Exchange of glutamate and gamma-aminobutyrate in a Lactobacillus strain. J Bacteriol 179:3362–3364[PubMed]
    [Google Scholar]
  26. Høiby N., Ciofu O., Bjarnsholt T. ( 2010). Pseudomonas aeruginosa biofilms in cystic fibrosis. Future Microbiol 5:1663–1674 [View Article][PubMed]
    [Google Scholar]
  27. Hu L. A., King S. C. ( 1998). Membrane topology of the Escherichia coli γ-aminobutyrate transporter: implications on the topography and mechanism of prokaryotic and eukaryotic transporters from the APC superfamily. Biochem J 336:69–76[PubMed]
    [Google Scholar]
  28. Jin Z., Mendu S. K., Birnir B. ( 2011). GABA is an effective immunomodulatory molecule. Amino Acids [View Article][PubMed]
    [Google Scholar]
  29. Johnson C. R., Muir D. G., Reysenbach A. L. ( 1991). Characteristic bacteria associated with surfaces of coralline algae: a hypothesis for bacterial induction of marine invertebrate larvae. Mar Ecol Prog Ser 74:281–294 [View Article]
    [Google Scholar]
  30. Kunert A., Losse J., Gruszin C., Hühn M., Kaendler K., Mikkat S., Volke D., Hoffmann R., Jokiranta T. S. & other authors ( 2007). Immune evasion of the human pathogen Pseudomonas aeruginosa: elongation factor Tuf is a factor H and plasminogen binding protein. J Immunol 179:2979–2988[PubMed] [CrossRef]
    [Google Scholar]
  31. Mesaros N., Nordmann P., Plésiat P., Roussel-Delvallez M., Van Eldere J., Glupczynski Y., Van Laethem Y., Jacobs F., Lebecque P. & other authors ( 2007). Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millennium. Clin Microbiol Infect 13:560–578 [View Article][PubMed]
    [Google Scholar]
  32. Meyer J. M., Neely A., Stintzi A., Georges C., Holder I. A. ( 1996). Pyoverdin is essential for virulence of Pseudomonas aeruginosa . Infect Immun 64:518–523[PubMed]
    [Google Scholar]
  33. Mezghani-Abdelmoula S., Khémiri A., Lesouhaitier O., Chevalier S., Orange N., Cazin L., Feuilloley M. G. J. ( 2004). Sequential activation of constitutive and inducible nitric oxide synthase (NOS) in rat cerebellar granule neurons by Pseudomonas fluorescens and invasive behaviour of the bacteria. Microbiol Res 159:355–363 [View Article][PubMed]
    [Google Scholar]
  34. Morin D., Grasland B., Vallée-Réhel K., Dufau C., Haras D. ( 2003). On-line high-performance liquid chromatography-mass spectrometric detection and quantification of N-acylhomoserine lactones, quorum sensing signal molecules, in the presence of biological matrices. J Chromatogr A 1002:79–92 [View Article][PubMed]
    [Google Scholar]
  35. Morse D. E., Duncan H., Hooker N., Baloun A., Young G. ( 1980). GABA induces behavioral and developmental metamorphosis in planktonic molluscan larvae. Fed Proc 39:3237–3241[PubMed]
    [Google Scholar]
  36. Mozrzymas J. W., Zarnowska E. D., Pytel M., Mercik K. ( 2003). Modulation of GABAA receptors by hydrogen ions reveals synaptic GABA transient and a crucial role of the desensitization process. J Neurosci 23:7981–7992[PubMed]
    [Google Scholar]
  37. O’Toole G. A., Kolter R. ( 1998). Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Mol Microbiol 30:295–304 [View Article][PubMed]
    [Google Scholar]
  38. Ochsner U. A., Vasil M. L., Alsabbagh E., Parvatiyar K., Hassett D. J. ( 2000). Role of the Pseudomonas aeruginosa oxyR-recG operon in oxidative stress defense and DNA repair: OxyR-dependent regulation of katB-ankB, ahpB, and ahpC-ahpF . J Bacteriol 182:4533–4544 [View Article][PubMed]
    [Google Scholar]
  39. Ostroff R. M., Wretlind B., Vasil M. L. ( 1989). Mutations in the hemolytic-phospholipase C operon result in decreased virulence of Pseudomonas aeruginosa PAO1 grown under phosphate-limiting conditions. Infect Immun 57:1369–1373[PubMed]
    [Google Scholar]
  40. Owens D. F., Kriegstein A. R. ( 2002). Is there more to GABA than synaptic inhibition?. Nat Rev Neurosci 3:715–727 [View Article][PubMed]
    [Google Scholar]
  41. Palanivelu R., Brass L., Edlund A. F., Preuss D. ( 2003). Pollen tube growth and guidance is regulated by POP2, an Arabidopsis gene that controls GABA levels. Cell 114:47–59 [View Article][PubMed]
    [Google Scholar]
  42. Petty F., Fulton M., Kramer G. L., Kram M., Davis L. L., Rush A. J. ( 1999). Evidence for the segregation of a major gene for human plasma GABA levels. Mol Psychiatry 4:587–589 [View Article][PubMed]
    [Google Scholar]
  43. Picot L., Abdelmoula S. M., Merieau A., Leroux P., Cazin L., Orange N., Feuilloley M. G. J. ( 2001). Pseudomonas fluorescens as a potential pathogen: adherence to nerve cells. Microbes Infect 3:985–995 [View Article][PubMed]
    [Google Scholar]
  44. Picot L., Chevalier S., Mezghani-Abdelmoula S., Merieau A., Lesouhaitier O., Leroux P., Cazin L., Orange N., Feuilloley M. G. J. ( 2003). Cytotoxic effects of the lipopolysaccharide from Pseudomonas fluorescens on neurons and glial cells. Microb Pathog 35:95–106 [View Article][PubMed]
    [Google Scholar]
  45. Picot L., Mezghani-Abdelmoula S., Chevalier S., Merieau A., Lesouhaitier O., Guerillon J., Cazin L., Orange N., Feuilloley M. G. J. ( 2004). Regulation of the cytotoxic effects of Pseudomonas fluorescens by growth temperature. Res Microbiol 155:39–46 [View Article][PubMed]
    [Google Scholar]
  46. Richard H. T., Foster J. W. ( 2003). Acid resistance in Escherichia coli . Adv Appl Microbiol 52:167–186 [View Article][PubMed]
    [Google Scholar]
  47. Rashid M. H., Kornberg A. ( 2000). Inorganic polyphosphatase is needed for swimming, swarming and twitching motilities of Pseudomonas aeruginosa . Proc Natl Acad Sci U S A 97:4885–4890 [View Article][PubMed]
    [Google Scholar]
  48. Schreiber K., Boes N., Eschbach M., Jaensch L., Wehland J., Bjarnsholt T., Givskov M., Hentzer M., Schobert M. ( 2006). Anaerobic survival of Pseudomonas aeruginosa by pyruvate fermentation requires an Usp-type stress protein. J Bacteriol 188:659–668 [View Article][PubMed]
    [Google Scholar]
  49. Schuster M., Greenberg E. P. ( 2006). A network of networks: quorum-sensing gene regulation in Pseudomonas aeruginosa . Int J Med Microbiol 296:73–81 [View Article][PubMed]
    [Google Scholar]
  50. Shelp B. J., Bown A. W., McLean M. D. ( 1999). Metabolism and functions of gamma-aminobutyric acid. Trends Plant Sci 4:446–452 [View Article][PubMed]
    [Google Scholar]
  51. Shelp B. J., Bown A. W., Faure D. ( 2006). Extracellular gamma-aminobutyrate mediates communication between plants and other organisms. Plant Physiol 142:1350–1352 [View Article][PubMed]
    [Google Scholar]
  52. Siragusa S., De Angelis M., Di Cagno R., Rizzello C. G., Coda R., Gobbetti M. ( 2007). Synthesis of gamma-aminobutyric acid by lactic acid bacteria isolated from a variety of Italian cheeses. Appl Environ Microbiol 73:7283–7290 [View Article][PubMed]
    [Google Scholar]
  53. Tunnicliff G., Malatynska E. ( 2003). Central GABAergic systems and depressive illness. Neurochem Res 28:965–976 [View Article][PubMed]
    [Google Scholar]
  54. van Delden C. ( 2007). Pseudomonas aeruginosa bloodstream infections: how should we treat them?. Int J Antimicrob Agents 30:Suppl. 1S71–S75 [View Article][PubMed]
    [Google Scholar]
  55. Vander Wauven C., Piérard A., Kley-Raymann M., Haas D. ( 1984). Pseudomonas aeruginosa mutants affected in anaerobic growth on arginine: evidence for a four-gene cluster encoding the arginine deiminase pathway. J Bacteriol 160:928–934[PubMed]
    [Google Scholar]
  56. Veron W., Lesouhaitier O., Pennanec X., Rehel K., Leroux P., Orange N., Feuilloley M. G. J. ( 2007). Natriuretic peptides affect Pseudomonas aeruginosa and specifically modify lipopolysaccharide biosynthesis. FEBS J 274:5852–5864 [View Article][PubMed]
    [Google Scholar]
  57. Williams P. L., Anderson G. L., Johnstone J. L., Nunn A. D., Tweedle M. F., Wedeking P. ( 2000). Caenorhabditis elegans as an alternative animal species. J Toxicol Environ Health A 61:641–647 [View Article][PubMed]
    [Google Scholar]
  58. Wittinghofer A., Guariguata R., Leberman R. ( 1983). Bacterial elongation factor Ts: isolation and reactivity with elongation factor Tu. J Bacteriol 153:1266–1271[PubMed]
    [Google Scholar]
  59. Wolf P., Elsässer-Beile U. ( 2009). Pseudomonas exotoxin A: from virulence factor to anti-cancer agent. Int J Med Microbiol 299:161–176 [View Article][PubMed]
    [Google Scholar]
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