1887

Abstract

We have found that FSS2, an infective endocarditis (IE) isolate, expresses a dipeptidyl-carboxypeptidase with activity homologous to angiotensin-converting enzyme (ACE). The carboxypeptidase activity was purified to homogeneity as a complex/aggregate from a bacterial surface extract and was also active as a 165 kDa monomer. The specific activity for the carboxypeptidase activity was eightfold higher than that for recombinant human ACE. Selected ACE inhibitors, captopril, lisinopril and enalapril, did not inhibit the ACE activity. The carboxypeptidase also hydrolysed the Aα and Bβ-chains of human fibrinogen, which resulted in impaired fibrin formation by thrombin. The gene encoding ACE carboxypeptidase activity was sequenced and the inferred polypeptide product showed 99 % amino acid homology to SGO_0566, , ‘challisin’ of CL1 Challis, and had no significant amino acid sequence homology to human ACE. Homologues of challisin ACE activity were commonly detected among the viridans group streptococci most often associated with IE.

Funding
This study was supported by the:
  • The Clive and Vera Ramaciotti Foundations
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.048710-0
2011-07-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/micro/157/7/2143.html?itemId=/content/journal/micro/10.1099/mic.0.048710-0&mimeType=html&fmt=ahah

References

  1. Antikainen J., Kuparinen V., Lähteenmäki K., Korhonen T. K. ( 2007). pH-dependent association of enolase and glyceraldehyde-3-phosphate dehydrogenase of Lactobacillus crispatus with the cell wall and lipoteichoic acids. J Bacteriol 189:4539–4543 [View Article][PubMed]
    [Google Scholar]
  2. Barrau K., Boulamery A., Imbert G., Casalta J.-P., Habib G., Messana T., Bonnet J. L., Rubinstein E., Raoult D. ( 2004). Causative organisms of infective endocarditis according to host status. Clin Microbiol Infect 10:302–308 [View Article][PubMed]
    [Google Scholar]
  3. Bensing B. A., López J. A., Sullam P. M. ( 2004). The Streptococcus gordonii surface proteins GspB and Hsa mediate binding to sialylated carbohydrate epitopes on the platelet membrane glycoprotein Ibα. Infect Immun 72:6528–6537 [View Article][PubMed]
    [Google Scholar]
  4. Bernstein K. E., Shen X. Z., Gonzalez-Villalobos R. A., Billet S., Okwan-Duodu D., Ong F. S., Fuchs S. ( 2011). Different in vivo functions of the two catalytic domains of angiotensin-converting enzyme (ACE). Curr Opin Pharmacol 11:105–111 [View Article][PubMed]
    [Google Scholar]
  5. Bondos S. E., Bicknell A. ( 2003). Detection and prevention of protein aggregation before, during, and after purification. Anal Biochem 316:223–231 [View Article][PubMed]
    [Google Scholar]
  6. Bonifait L., Vaillancourt K., Gottschalk M., Frenette M., Grenier D. ( 2011). Purification and characterization of the subtilisin-like protease of Streptococcus suis that contributes to its virulence. Vet Microbiol 148:333–340 [View Article][PubMed]
    [Google Scholar]
  7. Carey R. M., Siragy H. M. ( 2003). Newly recognized components of the renin–angiotensin system: potential roles in cardiovascular and renal regulation. Endocr Rev 24:261–271 [View Article][PubMed]
    [Google Scholar]
  8. Chaudhuri B., Paju S., Haase E. M., Vickerman M. M., Tanzer J. M., Scannapieco F. A. ( 2008). Amylase-binding protein B of Streptococcus gordonii is an extracellular dipeptidyl-peptidase. Infect Immun 76:4530–4537 [View Article][PubMed]
    [Google Scholar]
  9. Cork A. J., Jergic S., Hammerschmidt S., Kobe B., Pancholi V., Benesch J. L. P., Robinson C. V., Dixon N. E., Aquilina J. A., Walker M. J. ( 2009). Defining the structural basis of human plasminogen binding by streptococcal surface enolase. J Biol Chem 284:17129–17137 [View Article][PubMed]
    [Google Scholar]
  10. Davies J. R., Svensäter G., Herzberg M. C. ( 2009). Identification of novel LPXTG-linked surface proteins from Streptococcus gordonii . Microbiology 155:1977–1988 [View Article][PubMed]
    [Google Scholar]
  11. Deprèle C., Berthelot P., Lemetayer F., Comtet C., Fresard A., Cazorla C., Fascia P., Cathébras P., Chaumentin G. et al. ( 2004). Risk factors for systemic emboli in infective endocarditis. Clin Microbiol Infect 10:46–53 [View Article][PubMed]
    [Google Scholar]
  12. Fyhrquist F., Saijonmaa O. ( 2008). Renin–angiotensin system revisited. J Intern Med 264:224–236 [View Article][PubMed]
    [Google Scholar]
  13. Goldstein J. M., Banbula A., Kordula T., Mayo J. A., Travis J. ( 2001). Novel extracellular x-prolyl dipeptidyl-peptidase (DPP) from Streptococcus gordonii FSS2: an emerging subfamily of viridans streptococcal x-prolyl DPPs. Infect Immun 69:5494–5501 [View Article][PubMed]
    [Google Scholar]
  14. Goldstein J. M., Nelson D., Kordula T., Mayo J. A., Travis J. ( 2002). Extracellular arginine aminopeptidase from Streptococcus gordonii FSS2. Infect Immun 70:836–843 [View Article][PubMed]
    [Google Scholar]
  15. Goldstein J. M., Kordula T., Moon J. L., Mayo J. A., Travis J. ( 2005). Characterization of an extracellular dipeptidase from Streptococcus gordonii FSS2. Infect Immun 73:1256–1259 [View Article][PubMed]
    [Google Scholar]
  16. Harty D. W. S., Patrikakis M., Hume E. B. H., Oakey H. J., Knox K. W. ( 1993). The aggregation of human platelets by Lactobacillus species. J Gen Microbiol 139:2945–2951[PubMed] [CrossRef]
    [Google Scholar]
  17. Harty D. W. S., Mayo J. A., Cook S. L., Jacques N. A. ( 2000). Environmental regulation of glycosidase and peptidase production by Streptococcus gordonii FSS2. Microbiology 146:1923–1931[PubMed]
    [Google Scholar]
  18. Harty D. W. S., Chen Y., Simpson C. L., Berg T., Cook S. L., Mayo J. A., Hunter N., Jacques N. A. ( 2004). Characterisation of a novel homodimeric N-acetyl-β-d-glucosaminidase from Streptococcus gordonii . Biochem Biophys Res Commun 319:439–447 [View Article][PubMed]
    [Google Scholar]
  19. Jagroop I. A., Mikhailidis D. P. ( 2000). Angiotensin II can induce and potentiate shape change in human platelets: effect of losartan. J Hum Hypertens 14:581–585 [View Article][PubMed]
    [Google Scholar]
  20. Jakubovics N. S., Kerrigan S. W., Nobbs A. H., Strömberg N., van Dolleweerd C. J., Cox D. M., Kelly C. G., Jenkinson H. F. ( 2005). Functions of cell surface-anchored antigen I/II family and Hsa polypeptides in interactions of Streptococcus gordonii with host receptors. Infect Immun 73:6629–6638 [View Article][PubMed]
    [Google Scholar]
  21. Karlsson C., Mörgelin M., Collin M., Lood R., Andersson M. L., Schmidtchen A., Björck L., Frick I.-M. ( 2009). SufA – a bacterial enzyme that cleaves fibrinogen and blocks fibrin network formation. Microbiology 155:238–248 [View Article][PubMed]
    [Google Scholar]
  22. Kerrigan S. W., Jakubovics N. S., Keane C., Maguire P., Wynne K., Jenkinson H. F., Cox D. ( 2007). Role of Streptococcus gordonii surface proteins SspA/SspB and Hsa in platelet function. Infect Immun 75:5740–5747 [View Article][PubMed]
    [Google Scholar]
  23. Kinnby B., Booth N. A., Svensäter G. ( 2008). Plasminogen binding by oral streptococci from dental plaque and inflammatory lesions. Microbiology 154:924–931 [View Article][PubMed]
    [Google Scholar]
  24. Kozek-Langenecker S. A., Masaki T., Mohammad H., Green W., Mohammad S. F., Cheung A. K. ( 1999). Fibrinogen fragments and platelet dysfunction in uremia. Kidney Int 56:299–305 [View Article][PubMed]
    [Google Scholar]
  25. Lord S. T. ( 2011). Molecular mechanisms affecting fibrin structure and stability. Arterioscler Thromb Vasc Biol 31:494–499 [View Article][PubMed]
    [Google Scholar]
  26. Moreillon P., Que Y.-A. ( 2004). Infective endocarditis. Lancet 363:139–149 [View Article][PubMed]
    [Google Scholar]
  27. Nelson D., Goldstein J. M., Boatright K., Harty D. W. S., Cook S. L., Hickman P. J., Potempa J., Travis J., Mayo J. A. ( 2001). pH-regulated secretion of a glyceraldehyde-3-phosphate dehydrogenase from Streptococcus gordonii FSS2: purification, characterization, and cloning of the gene encoding this enzyme. J Dent Res 80:371–377 [View Article][PubMed]
    [Google Scholar]
  28. Petersen H. J., Keane C., Jenkinson H. F., Vickerman M. M., Jesionowski A., Waterhouse J. C., Cox D., Kerrigan S. W. ( 2010). Human platelets recognize a novel surface protein, PadA, on Streptococcus gordonii through a unique interaction involving fibrinogen receptor GPIIbIIIa. Infect Immun 78:413–422 [View Article][PubMed]
    [Google Scholar]
  29. Rivière G., Michaud A., Corradi H. R., Sturrock E. D., Ravi Acharya K., Cogez V., Bohin J.-P., Vieau D., Corvol P. ( 2007). Characterization of the first angiotensin-converting like enzyme in bacteria: ancestor ACE is already active. Gene 399:81–90 [View Article][PubMed]
    [Google Scholar]
  30. Senchenkova E. Y., Russell J., Almeida-Paula L. D., Harding J. W., Granger D. N. ( 2010). Angiotensin II-mediated microvascular thrombosis. Hypertension 56:1089–1095 [View Article][PubMed]
    [Google Scholar]
  31. Stinson M. W., Alder S., Kumar S. ( 2003). Invasion and killing of human endothelial cells by viridans group streptococci. Infect Immun 71:2365–2372 [View Article][PubMed]
    [Google Scholar]
  32. Takahashi Y., Yajima A., Cisar J. O., Konishi K. ( 2004). Functional analysis of the Streptococcus gordonii DL1 sialic acid-binding adhesin and its essential role in bacterial binding to platelets. Infect Immun 72:3876–3882 [View Article][PubMed]
    [Google Scholar]
  33. Turner L. S., Kanamoto T., Unoki T., Munro C. L., Wu H., Kitten T. ( 2009). Comprehensive evaluation of Streptococcus sanguinis cell wall-anchored proteins in early infective endocarditis. Infect Immun 77:4966–4975 [View Article][PubMed]
    [Google Scholar]
  34. Vriesema A. J., Dankert J., Zaat S. A. J. ( 2000). A shift from oral to blood pH is a stimulus for adaptive gene expression of Streptococcus gordonii CH1 and induces protection against oxidative stress and enhanced bacterial growth by expression of msrA . Infect Immun 68:1061–1068 [View Article][PubMed]
    [Google Scholar]
  35. Wang B.-Y., Kuramitsu H. K. ( 2005). Interactions between oral bacteria: inhibition of Streptococcus mutans bacteriocin production by Streptococcus gordonii . Appl Environ Microbiol 71:354–362 [View Article][PubMed]
    [Google Scholar]
  36. Watanabe T., Barker T. A., Berk B. C. ( 2005). Angiotensin II and the endothelium: diverse signals and effects. Hypertension 45:163–169 [View Article][PubMed]
    [Google Scholar]
  37. Weisel J. W. ( 2004). The mechanical properties of fibrin for basic scientists and clinicians. Biophys Chem 112:267–276 [View Article][PubMed]
    [Google Scholar]
  38. Wösten-van Asperen R. M., Lutter R., Specht P. A. C., van Woensel J. B., van der Loos C. M., Florquin S., Lachmann B., Bos A. P. ( 2010). Ventilator-induced inflammatory response in lipopolysaccharide-exposed rat lung is mediated by angiotensin-converting enzyme. Am J Pathol 176:2219–2227 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.048710-0
Loading
/content/journal/micro/10.1099/mic.0.048710-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Supplementary material 2

PDF

Supplementary material 3

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error