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PMID: 10722574 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Secreted enzymatic activities of wild-type and pilD-deficient Legionella pneumophila.

Infection and immunity ·Vol. 68 ·No. 4 ·2000-04-00 ·Pages 1855-63

Aragon V, Kurtz S, Flieger A, Neumeister B, Cianciotto NP

Abstract

Legionella pneumophila, the agent of Legionnaires' disease, is an intracellular pathogen of protozoa and macrophages. Previously, we had determined that the Legionella pilD gene is involved in type IV pilus biogenesis, type II protein secretion, intracellular infection, and virulence. Since the loss of pili and a protease do not account for the infection defect exhibited by a pilD-deficient strain, we sought to define other secreted proteins absent in the mutant. Based upon the release of p-nitrophenol (pNP) from p-nitrophenyl phosphate, acid phosphatase activity was detected in wild-type but not in pilD mutant supernatants. Mutant supernatants also did not release either pNP from p-nitrophenyl caprylate and palmitate or free fatty acid from 1-monopalmitoylglycerol, suggesting that they lack a lipase-like activity. However, since wild-type samples failed to release free fatty acids from 1,2-dipalmitoylglycerol or to cleave a triglyceride derivative, this secreted activity should be viewed as an esterase-monoacylglycerol lipase. The mutant supernatants were defective for both release of free fatty acids from phosphatidylcholine and degradation of RNA, indicating that PilD-negative bacteria lack a secreted phospholipase A (PLA) and nuclease. Finally, wild-type but not mutant supernatants liberated pNP from p-nitrophenylphosphorylcholine (pNPPC). Characterization of a new set of mutants defective for pNPPC-hydrolysis indicated that this wild-type activity is due to a novel enzyme, as opposed to a PLC or another known enzyme. Some, but not all, of these mutants were greatly impaired for intracellular infection, suggesting that a second regulator or processor of the pNPPC hydrolase is critical for L. pneumophila virulence.

MeSH Terms
Bacterial Proteins/genetics,metabolism,physiology Endopeptidases Genetic Complementation Test Humans Legionella pneumophila/enzymology Macrophages/microbiology Monoacylglycerol Lipases/metabolism Mutagenesis Mutation Phospholipases A/metabolism Phosphoric Diester Hydrolases/metabolism Ribonucleases/metabolism Substrate Specificity Time Factors U937 Cells
Chemicals
Bacterial Proteins Ribonucleases Monoacylglycerol Lipases Phospholipases A 4-nitrophenylphosphorylcholine phosphodiesterase Phosphoric Diester Hydrolases Endopeptidases prepilin peptidase protein, Bacteria
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Aragon V
Department of Microbiology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Kurtz S
Flieger A
Neumeister B
Cianciotto N P
References (75)
75 references, click to expand
  1. Identification of two genes with prepilin-like leader sequences involved in type 4 fimbrial biogenesis in Pseudomonas aeruginosa.
    J Bacteriol. 1996 Jul;178(13):3809-17 PMID: 8682785
  2. Cloning, sequencing, and role in virulence of two phospholipases (A1 and C) from mesophilic Aeromonas sp. serogroup O:34.
    Infect Immun. 1999 Aug;67(8):4008-13 PMID: 10417167
  3. Identification of fimbrial assembly genes from Dichelobacter nodosus: evidence that fimP encodes the type-IV prepilin peptidase.
    Gene. 1995 Aug 8;161(1):21-6 PMID: 7642131
  4. Comparative cytotoxicities of selected minor dietary non-nutrients with chemopreventive properties.
    Cancer Lett. 1993 Sep 30;73(2-3):127-33 PMID: 8221624
  5. Characterization and sequencing of a respiratory burst-inhibiting acid phosphatase from Francisella tularensis.
    J Biol Chem. 1996 May 3;271(18):10973-83 PMID: 8631917
  6. Common themes in microbial pathogenicity revisited.
    Microbiol Mol Biol Rev. 1997 Jun;61(2):136-69 PMID: 9184008
  7. The determination of acid and alkaline phosphatase using p-nitrophenyl phosphate as substrate.
    Am J Med Technol. 1954 Jul-Aug;20(4):244-53 PMID: 13180523
  8. Identification and characterization of xcpR encoding a subunit of the general secretory pathway necessary for dodecane degradation in Acinetobacter calcoaceticus ADP1.
    J Bacteriol. 1997 Jul;179(14):4631-4 PMID: 9226277
  9. Legionnaires disease: historical perspective.
    Clin Microbiol Rev. 1988 Jan;1(1):60-81 PMID: 3060246
  10. A single bifunctional enzyme, PilD, catalyzes cleavage and N-methylation of proteins belonging to the type IV pilin family.
    Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2404-8 PMID: 8096341
  11. Construction of an alkaline phosphatase fusion-generating transposon, mTn10phoA.
    Gene. 1996 Apr 17;170(1):147-8 PMID: 8621078
  12. Critical evaluation of p-nitrophenylphosphorylcholine (p-NPPC) as artificial substrate for the detection of phospholipase C*
    Enzyme Microb Technol. 2000 Mar 1;26(5-6):451-458 PMID: 10713220
  13. Cloning of an Aeromonas hydrophila type IV pilus biogenesis gene cluster: complementation of pilus assembly functions and characterization of a type IV leader peptidase/N-methyltransferase required for extracellular protein secretion.
    Mol Microbiol. 1996 Feb;19(4):857-69 PMID: 8820654
  14. Legionella pneumophila mip gene potentiates intracellular infection of protozoa and human macrophages.
    Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5188-91 PMID: 1594630
  15. The Legionella pneumophila major secretory protein, a protease, is not required for intracellular growth or cell killing.
    Infect Immun. 1990 Aug;58(8):2585-92 PMID: 2164510
  16. Bacterial biocatalysts: molecular biology, three-dimensional structures, and biotechnological applications of lipases.
    Annu Rev Microbiol. 1999;53:315-51 PMID: 10547694
  17. (3-sn-Phosphatidyl)cholines (lecithins) in amniotic fluid.
    Clin Chem. 1983 Nov;29(11):1951-4 PMID: 6627632
  18. Phospholipase C assay using p-nitrophenylphosphoryl-choline together with sorbitol and its application to studying the metal and detergent requirement of the enzyme.
    Anal Biochem. 1976 Sep;75(1):281-9 PMID: 183567
  19. Identification and temperature regulation of Legionella pneumophila genes involved in type IV pilus biogenesis and type II protein secretion.
    Infect Immun. 1998 Apr;66(4):1776-82 PMID: 9529113
  20. Cloning and expression of Legionella pneumophila antigens in Escherichia coli.
    Infect Immun. 1984 May;44(2):222-7 PMID: 6325347
  21. Exotoxin activity associated with the Legionnaires disease bacterium.
    J Clin Microbiol. 1979 Mar;9(3):453-6 PMID: 572374
  22. Cleavage, methylation, and localization of the Pseudomonas aeruginosa export proteins XcpT, -U, -V, and -W.
    J Bacteriol. 1993 Jul;175(14):4375-82 PMID: 8331069
  23. Virulence factors of the family Legionellaceae.
    Microbiol Rev. 1992 Mar;56(1):32-60 PMID: 1579112
  24. Endochitinase is transported to the extracellular milieu by the eps-encoded general secretory pathway of Vibrio cholerae.
    J Bacteriol. 1998 Nov;180(21):5591-600 PMID: 9791107
  25. Purification, gene cloning, amino acid sequence analysis, and expression of an extracellular lipase from an Aeromonas hydrophila human isolate.
    Appl Environ Microbiol. 1993 Aug;59(8):2411-7 PMID: 8368830
  26. Identification of an additional member of the secretin superfamily of proteins in Pseudomonas aeruginosa that is able to function in type II protein secretion.
    Mol Microbiol. 1998 Jun;28(6):1235-46 PMID: 9680212
  27. Fimbrial biogenesis genes of Pseudomonas aeruginosa: pilW and pilX increase the similarity of type 4 fimbriae to the GSP protein-secretion systems and pilY1 encodes a gonococcal PilC homologue.
    Mol Microbiol. 1996 Oct;22(1):161-73 PMID: 8899718
  28. A new, sensitive determination of phosphate.
    Anal Biochem. 1969 Jul;30(1):51-7 PMID: 5791084
  29. Random mutagenesis of Legionella pneumophila with mini-Tn10.
    FEMS Microbiol Lett. 1994 Nov 15;124(1):107-11 PMID: 8001761
  30. Photometric determination of phospholipase A.
    J Clin Chem Clin Biochem. 1986 Nov;24(11):871-5 PMID: 2433381
  31. Extracellular enzymes of Legionella pneumophila.
    Infect Immun. 1981 Aug;33(2):632-5 PMID: 6268549
  32. A spectrophotometric assay of Zn(2+)-glycerophosphorylcholine phosphocholine phosphodiesterase using p-nitrophenylphosphorylcholine.
    Anal Biochem. 1992 Jun;203(2):201-5 PMID: 1384383
  33. Legionellosis: ecological factors of an environmentally 'new' disease.
    Zentralbl Hyg Umweltmed. 1994 Jun;195(5-6):470-82 PMID: 7916875
  34. Improved semiselective medium for isolation of Legionella pneumophila from contaminated clinical and environmental specimens.
    J Clin Microbiol. 1981 Sep;14(3):298-303 PMID: 7287886
  35. Biogenesis of the bundle-forming pilus of enteropathogenic Escherichia coli: reconstitution of fimbriae in recombinant E. coli and role of DsbA in pilin stability--a review.
    Gene. 1997 Jun 11;192(1):33-8 PMID: 9224871
  36. Identification of the Vibrio cholerae type 4 prepilin peptidase required for cholera toxin secretion and pilus formation.
    Mol Microbiol. 1998 Sep;29(6):1481-92 PMID: 9781884
  37. Glycogen, hyaluronate, and some other polysaccharides greatly enhance the formation of exolipase by Serratia marcescens.
    J Bacteriol. 1979 Jun;138(3):663-70 PMID: 222724
  38. Hydrolysis of p-nitrophenylphosphorylcholine by alkaline phosphatase and phospholipase C from rabbit sperm-acrosome.
    Biochem Biophys Res Commun. 1982 Oct 15;108(3):1120-5 PMID: 7181885
  39. Elastase and the LasA protease of Pseudomonas aeruginosa are secreted with their propeptides.
    J Biol Chem. 1998 Nov 13;273(46):30225-31 PMID: 9804780
  40. Legionella micdadei phosphatase catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate in human neutrophils.
    Arch Biochem Biophys. 1988 Aug 15;265(1):94-104 PMID: 2843104
  41. Structure-function relationship of type-IV prepilin peptidase of Pseudomonas aeruginosa--a review.
    Gene. 1997 Jun 11;192(1):117-21 PMID: 9224881
  42. The pilE gene product of Pseudomonas aeruginosa, required for pilus biogenesis, shares amino acid sequence identity with the N-termini of type 4 prepilin proteins.
    Mol Microbiol. 1994 Sep;13(6):973-85 PMID: 7854130
  43. Conservation of genes encoding components of a type IV pilus assembly/two-step protein export pathway in Neisseria gonorrhoeae.
    Mol Microbiol. 1993 Apr;8(2):357-68 PMID: 8100347
  44. Protein secretion in Pseudomonas aeruginosa: characterization of seven xcp genes and processing of secretory apparatus components by prepilin peptidase.
    Mol Microbiol. 1992 May;6(9):1121-31 PMID: 1588814
  45. A phospholipase C from the Dallas 1E strain of Legionella pneumophila serogroup 5: purification and characterization of conditions for optimal activity with an artificial substrate.
    J Gen Microbiol. 1988 Feb;134(2):489-98 PMID: 3171547
  46. Infection of macrophage-like cells by Legionella species that have not been associated with disease.
    Infect Immun. 1996 Oct;64(10):4381-4 PMID: 8926117
  47. Cytolytic and phospholipase C activity in Legionella species.
    J Gen Microbiol. 1985 Jun;131(6):1383-91 PMID: 4045420
  48. Multiple roles of the pilus biogenesis protein pilD: involvement of pilD in excretion of enzymes from Pseudomonas aeruginosa.
    J Bacteriol. 1991 Feb;173(3):1175-80 PMID: 1671384
  49. The complete general secretory pathway in gram-negative bacteria.
    Microbiol Rev. 1993 Mar;57(1):50-108 PMID: 8096622
  50. The secretion apparatus of Pseudomonas aeruginosa: identification of a fifth pseudopilin, XcpX (GspK family).
    Mol Microbiol. 1998 Jan;27(1):31-40 PMID: 9466253
  51. Phosphatase-negative mutants of Legionella pneumophila and their behavior in mammalian cell infection.
    Microb Pathog. 1994 Jul;17(1):51-62 PMID: 7861953
  52. Insertion mutagenesis of XpsD, an outer-membrane protein involved in extracellular protein secretion in Xanthomonas campestris pv. campestris.
    Microbiology. 1998 Jun;144 ( Pt 6):1479-86 PMID: 9639918
  53. Effects of an isogenic Zn-metalloprotease-deficient mutant of Legionella pneumophila in a guinea-pig pneumonia model.
    Mol Microbiol. 1994 Jun;12(5):693-705 PMID: 8052122
  54. Expression of multiple pili by Legionella pneumophila: identification and characterization of a type IV pilin gene and its role in adherence to mammalian and protozoan cells.
    Infect Immun. 1998 Apr;66(4):1768-75 PMID: 9529112
  55. The molecular ecology of legionellae.
    Trends Microbiol. 1996 Jul;4(7):286-90 PMID: 8829338
  56. Specificity of the lipase-specific foldases of gram-negative bacteria and the role of the membrane anchor.
    Mol Gen Genet. 1999 Jun;261(4-5):770-6 PMID: 10394914
  57. An iron- and fur-repressed Legionella pneumophila gene that promotes intracellular infection and encodes a protein with similarity to the Escherichia coli aerobactin synthetases.
    Infect Immun. 1997 Jan;65(1):133-43 PMID: 8975903
  58. Macromolecular assembly and secretion across the bacterial cell envelope: type II protein secretion systems.
    J Mol Biol. 1998 Jun 12;279(3):485-99 PMID: 9641973
  59. Product of the Pseudomonas aeruginosa gene pilD is a prepilin leader peptidase.
    Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3281-5 PMID: 1901657
  60. Phospholipase A of Yersinia enterocolitica contributes to pathogenesis in a mouse model.
    Infect Immun. 1998 Aug;66(8):3941-51 PMID: 9673284
  61. The prepilin peptidase is required for protein secretion by and the virulence of the intracellular pathogen Legionella pneumophila.
    Mol Microbiol. 1999 Feb;31(3):959-70 PMID: 10048038
  62. A Legionella pneumophila gene encoding a species-specific surface protein potentiates initiation of intracellular infection.
    Infect Immun. 1989 Apr;57(4):1255-62 PMID: 2925251
  63. General secretion pathway (eps) genes required for toxin secretion and outer membrane biogenesis in Vibrio cholerae.
    J Bacteriol. 1997 Nov;179(22):6994-7003 PMID: 9371445
  64. GSP-dependent protein secretion in gram-negative bacteria: the Xcp system of Pseudomonas aeruginosa.
    FEMS Microbiol Rev. 1998 Sep;22(3):177-98 PMID: 9818381
  65. The pilH gene encodes an ABC transporter homologue required for type IV pilus biogenesis and social gliding motility in Myxococcus xanthus.
    Mol Microbiol. 1998 Sep;29(5):1249-61 PMID: 9767592
  66. Legionella pneumophila contains a type II general secretion pathway required for growth in amoebae as well as for secretion of the Msp protease.
    Infect Immun. 1999 Jul;67(7):3662-6 PMID: 10377156
  67. The vacB gene required for virulence in Shigella flexneri and Escherichia coli encodes the exoribonuclease RNase R.
    J Biol Chem. 1998 Jun 5;273(23):14077-80 PMID: 9603904
  68. Radial diffusion in gel for micro determination of enzymes. I. Muramidase, alpha-amylase, DNase 1, RNase A, acid phosphatase, and alkaline phosphatase.
    Anal Biochem. 1972 Apr;46(2):502-33 PMID: 4502712
  69. Interactions between macrophages and Legionella pneumophila.
    Curr Top Microbiol Immunol. 1992;181:265-82 PMID: 1424783
  70. Purification and characterization of an extracellular protease of Legionella pneumophila.
    Infect Immun. 1986 Mar;51(3):736-43 PMID: 3512431
  71. Enzymatic profile of Legionella pneumophilia.
    J Clin Microbiol. 1981 Mar;13(3):423-6 PMID: 6165735
  72. Protein secretion in Pseudomonas aeruginosa: molecular cloning and characterization of the xcp-1 gene.
    J Bacteriol. 1989 Aug;171(8):4342-8 PMID: 2502537
  73. Enzymatic activities of Legionella pneumophila and Legionella-like organisms.
    J Clin Microbiol. 1982 Jan;15(1):175-7 PMID: 7186905
  74. Products of three accessory genes, pilB, pilC, and pilD, are required for biogenesis of Pseudomonas aeruginosa pili.
    J Bacteriol. 1990 Jun;172(6):2911-9 PMID: 1971619
  75. Genetic characterization of a new type IV-A pilus gene cluster found in both classical and El Tor biotypes of Vibrio cholerae.
    Infect Immun. 1999 Mar;67(3):1393-404 PMID: 10024587
Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
Published
2000-04-00
Pages
1855-63
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC97358
Subset
IM
Grants
NIAID NIH HHS · R01 AI043987 · United States
NIAID NIH HHS · AI43987 · United States
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