Skip to main content
Log in

The mystery of the fourth clone: comparative genomic analysis of four non-typeable Streptococcus pneumoniae strains with different susceptibilities to optochin

  • Original Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Optochin-resistant pneumococci can be rarely caught in clinical microbiology laboratories because of the routine identification of all such strains as viridans group non-pneumococci. We were lucky to find four non-typeable Streptococcus pneumoniae clones demonstrating the different susceptibilities to optochin: one of them (Spn_13856) was resistant to optochin, while the other three (Spn_1719, Spn_27, and Spn_2298) were susceptible. Whole genome nucleotide sequences of these strains were compared to reveal the differences between the optochin-resistant and optochin-susceptible strains. Two adjacent genes coding maltose O-acetyltransferase and uridine phosphorylase which were presented in the genomes of all optochin-susceptible strains and missed in the optochin-resistant strain were revealed. Non-synonymous substitutions in 14 protein-coding genes were discovered, including the Ala49Ser mutation in the C-subunit of the F0 part of the ATP synthase rotor usually associated with pneumococcal optochin resistance. Modeling of a process of optochin interaction with the F0 part of the ATP synthase rotor indicates that the complex of optochin with “domain C” composed by wild-type C-subunits is more stable than the same complex composed of Ala49Ser mutant C-subunits.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Kontiainen S, Sivonen A (1987) Optochin resistance in Streptococcus pneumoniae strains isolated from blood and middle ear fluid. Eur J Clin Microbiol 6:422–424

    Article  PubMed  CAS  Google Scholar 

  2. Muñoz R, Fenoll A, Vicioso D, Casal J (1990) Optochin-resistant variants of Streptococcus pneumoniae. Diagn Microbiol Infect Dis 13:63–66

    Article  PubMed  Google Scholar 

  3. Tsai HY, Hsueh PR, Teng LJ, Lee PI, Huang LM, Lee CY, Luh KT (2000) Bacteremic pneumonia caused by a single clone of Streptococcus pneumoniae with different optochin susceptibilities. J Clin Microbiol 38:458–459

    PubMed  CAS  PubMed Central  Google Scholar 

  4. Aguiar SI, Frias MJ, Santos L, Melo-Cristino J, Ramirez M; Portuguese Surveillance Group for Study of Respiratory Pathogens (2006) Emergence of optochin resistance among Streptococcus pneumoniae in Portugal. Microb Drug Resist 12:239–245

    Article  PubMed  CAS  Google Scholar 

  5. Nunes S, Sá-Leão R, de Lencastre H (2008) Optochin resistance among Streptococcus pneumoniae strains colonizing healthy children in Portugal. J Clin Microbiol 46:321–324

    Article  PubMed  PubMed Central  Google Scholar 

  6. Karunanayake L, Tennakoon C (2011) Optochin-resistant Streptococcus pneumoniae. Ceylon Med J 56:84

    Article  PubMed  CAS  Google Scholar 

  7. Kacou-N’douba A, Okpo SC, Ekaza E, Pakora A, Koffi S, Dosso M (2010) Emergence of optochin resistance among S. pneumoniae strains colonizing healthy children in Abidjan. Indian J Med Microbiol 28:80–81

    Article  PubMed  Google Scholar 

  8. Nagata M, Ueda O, Shobuike T, Muratani T, Aoki Y, Miyamoto H (2012) Emergence of optochin resistance among Streptococcus pneumoniae in Japan. Open J Med Microbiol 2:8–15

    Article  Google Scholar 

  9. Fenoll A, Muñoz R, García E, de la Campa AG (1994) Molecular basis of the optochin-sensitive phenotype of pneumococcus: characterization of the genes encoding the F0 complex of the Streptococcus pneumoniae and Streptococcus oralis H(+)-ATPases. Mol Microbiol 12:587–598

    Article  PubMed  CAS  Google Scholar 

  10. Cogné N, Claverys J, Denis F, Martin C (2000) A novel mutation in the alpha-helix 1 of the C subunit of the F(1)/F(0) ATPase responsible for optochin resistance of a Streptococcus pneumoniae clinical isolate. Diagn Microbiol Infect Dis 38:119–121

    Article  PubMed  Google Scholar 

  11. Pikis A, Campos JM, Rodriguez WJ, Keith JM (2001) Optochin resistance in Streptococcus pneumoniae: mechanism, significance, and clinical implications. J Infect Dis 184:582–590

    Article  PubMed  CAS  Google Scholar 

  12. Dias CA, Agnes G, Frazzon APG, Kruger FD, d’Azevedo PA, Carvalho Mda GS, Facklam RR, Teixeira LM (2007) Diversity of mutations in the atpC gene coding for the C subunit of F0F1 ATPase in clinical isolates of optochin-resistant Streptococcus pneumoniae from Brazil. J Clin Microbiol 45:3065–3067

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  14. Enright MC, Spratt BG (1998) A multilocus sequence typing scheme for Streptococcus pneumoniae: identification of clones associated with serious invasive disease. Microbiology 144:3049–3060

    Article  PubMed  CAS  Google Scholar 

  15. Bishop CJ, Aanensen DM, Jordan GE, Kilian M, Hanage WP, Spratt BG (2009) Assigning strains to bacterial species via the internet. BMC Biol 7:3

    Article  PubMed  PubMed Central  Google Scholar 

  16. Ikryannikova LN, Lapin KN, Malakhova MV, Filimonova AV, Ilina EN, Dubovickaya VA, Sidorenko SV, Govorun VM (2011) Misidentification of alpha-hemolytic streptococci by routine tests in clinical practice. Infect Genet Evol 11:1709–1715

    Article  PubMed  CAS  Google Scholar 

  17. Eddy SR (2004) Where did the BLOSUM62 alignment score matrix come from? Nat Biotechnol 22:1035–1036

    Article  PubMed  CAS  Google Scholar 

  18. Boos W, Shuman H (1998) Maltose/maltodextrin system of Escherichia coli: transport, metabolism, and regulation. Microbiol Mol Biol Rev 62:204–229

    PubMed  CAS  PubMed Central  Google Scholar 

  19. Matsumoto N, Yamada M, Kurakata Y, Yoshida H, Kamitori S, Nishikawa A, Tonozuka T (2009) Crystal structures of open and closed forms of cyclo/maltodextrin-binding protein. FEBS J 276:3008–3019

    Article  PubMed  CAS  Google Scholar 

  20. Goldsmith DB, Crosti G, Dwivedi B, McDaniel LD, Varsani A, Suttle CA, Weinbauer MG, Sandaa RA, Breitbart M (2011) Development of phoH as a novel signature gene for assessing marine phage diversity. Appl Environ Microbiol 77:7730–7739

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Derré I, Rapoport G, Devine K, Rose M, Msadek T (1999) ClpE, a novel type of HSP100 ATPase, is part of the CtsR heat shock regulon of Bacillus subtilis. Mol Microbiol 32:581–593

    Article  PubMed  Google Scholar 

  22. Miethke M, Hecker M, Gerth U (2006) Involvement of Bacillus subtilis ClpE in CtsR degradation and protein quality control. J Bacteriol 188:4610–4619

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  23. Kaval KG, Halbedel S (2012) Architecturally the same, but playing a different game: the diverse species-specific roles of DivIVA proteins. Virulence 3:406–407

    Article  PubMed  PubMed Central  Google Scholar 

  24. Nolivos S, Sherratt D (2014) The bacterial chromosome: architecture and action of bacterial SMC and SMC-like complexes. FEMS Microbiol Rev 38:380–392

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Procko E, O’Mara ML, Bennett WFD, Tieleman DP, Gaudet R (2009) The mechanism of ABC transporters: general lessons from structural and functional studies of an antigenic peptide transporter. FASEB J 23:1287–1302

    Article  PubMed  CAS  Google Scholar 

  26. Muñoz R, García E, De la Campa AG (1996) Quinine specifically inhibits the proteolipid subunit of the F0F1 H+ -ATPase of Streptococcus pneumoniae. J Bacteriol 178:2455–2458

    PubMed  PubMed Central  Google Scholar 

  27. Pinto TCA, Souza ARV, de Pina SECM, Costa NS, Neto AAB, Neves FPG, Merquior VLC, Dias CAG, Peralta JM, Teixeira LM (2013) Optochin-resistant Streptococcus pneumoniae: phenotypic and molecular characterization of isolates from Brazil with description of five novel mutations in the atpC gene. J Clin Microbiol 51:3242–3249

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. Romanovsky YM, Tikhonov AN (2010) Molecular energy transducers of the living cell. Proton ATP synthase: a rotating molecular motor. Phys Usp 53:893–914

    Article  CAS  Google Scholar 

  29. Martín-Galiano AJ, Gorgojo B, Kunin CM, de la Campa AG (2002) Mefloquine and new related compounds target the F(0) complex of the F(0)F(1) H(+)-ATPase of Streptococcus pneumoniae. Antimicrob Agents Chemother 46:1680–1687

    Article  PubMed  PubMed Central  Google Scholar 

  30. Cortes PR, Piñas GE, Albarracin Orio AG, Echenique JR (2008) Subinhibitory concentrations of penicillin increase the mutation rate to optochin resistance in Streptococcus pneumoniae. J Antimicrob Chemother 62:973–977

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Russian Science Foundation (RSF), grant no. 15-15-00158. This publication made use of the Viridans.eMLSA.net database (http://viridans.emlsa.net/) and the Streptococcus pneumoniae MLST database (http://spneumoniae.mlst.net/), hosted at the Department of Infectious Disease Epidemiology, Imperial College London.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L. N. Ikryannikova.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

Submission of manuscript: All authors have contributed sufficiently to the scientific work presented in this manuscript and, therefore, share collective responsibility for the results. All authors agree with the final version of the manuscript under submission. This manuscript is not under consideration by any other journal. No parts of the data have been previously submitted for publication.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ikryannikova, L.N., Ischenko, D.S., Lominadze, G.G. et al. The mystery of the fourth clone: comparative genomic analysis of four non-typeable Streptococcus pneumoniae strains with different susceptibilities to optochin. Eur J Clin Microbiol Infect Dis 35, 119–130 (2016). https://doi.org/10.1007/s10096-015-2516-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-015-2516-5

Keywords

Navigation