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Biochemistry (Moscow)

, Volume 80, Issue 7, pp 901–914 | Cite as

O-Antigen modifications providing antigenic diversity of Shigella flexneri and underlying genetic mechanisms

  • Y. A. KnirelEmail author
  • Qiangzheng SunEmail author
  • S. N. Senchenkova
  • A. V. Perepelov
  • A. S. Shashkov
  • Jianguo XuEmail author
Review

Abstract

O-Antigens (O-specific polysaccharides) of Shigella flexneri, a primary cause of shigellosis, are distinguished by a wide diversity of chemical modifications following the oligosaccharide O-unit assembly. The present review is devoted to structural, serological, and genetic aspects of these modifications, including O-acetylation and phosphorylation with phosphoethanolamine that have been identified recently. The modifications confer the host with specific immunodeterminants (O-factors or O-antigen epitopes), which accounts for the antigenic diversity of S. flexneri considered as a virulence factor of the pathogen. Totally, 30 O-antigen variants have been recognized in these bacteria, the corresponding O-factors characterized using specific antibodies, and a significant extension of the serotyping scheme of S. flexneri on this basis is suggested. Multiple genes responsible for the O-antigen modifications and the resultant serotype conversions of S. flexneri have been identified. The genetic mechanisms of the O-antigen diversification by acquisition of mobile genetic elements, including prophages and plasmids, followed occasionally by gene mobilization and inactivation have been revealed. These findings further our understanding of the genetics and antigenicity of S. flexneri and assist control of shigellosis.

Keywords

Shigella flexneri O-antigen O-polysaccharide structure serotype-converting bacteriophage transposon plasmid serotyping immunodeterminant 

Abbreviation

GalA

galacturonic acid

GalNAc

2-acetamido-2-deoxygalactose

GlcNAc

2-acetamido-2-deoxyglucose

IS

insertion sequence

LPS

lipopolysaccharide

PEtN

phosphoethanolamine

Rha

rhamnose

Sf

Shigella flexneri

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References

  1. 1.
    Bardhan, P., Faruque, A. S., Naheed, A., and Sack, D. A. (2010) Decrease in shigellosis-related deaths without Shigella spp.-specific interventions, Asia, Emerg. Infect. Dis., 16, 1718–1723.PubMedCrossRefGoogle Scholar
  2. 2.
    Schroeder, G. N., and Hilbi, H. (2008) Molecular pathogenesis of Shigella spp.: controlling host cell signaling, invasion, and death by type III secretion, Clin. Microbiol. Rev., 21, 134–156.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Ewing, W. H., and Lindberg, A. A. (1984) Serology of Shigella, Methods Microbiol., 14, 113–142.CrossRefGoogle Scholar
  4. 4.
    Pupo, G. M., Lan, R., and Reeves, P. R. (2000) Multiple independent origins of Shigella clones of Escherichia coli and convergent evolution of many of their characteristics, Proc. Natl. Acad. Sci. USA, 97, 10567–10572.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Kotloff, K. L., Winickoff, J. P., Ivanoff, B., Clemens, J. D., Swerdlow, D. L., Sansonetti, P. J., Adak, G. K., and Levine, M. M. (1999) Global burden of Shigella infections: implications for vaccine development and implementation of control strategies, Bull. World Health Organ., 77, 651666.Google Scholar
  6. 6.
    Shiferaw, B., Shallow, S., Marcus, R., Segler, S., Soderlund, D., Hardnett, F. P., and Van Gilder, T (2004) Trends in population-based active surveillance for shigellosis and demographic variability in FoodNet sites, 19961999, Clin. Infect. Dis., 38 (Suppl. 3), S175–S180.PubMedCrossRefGoogle Scholar
  7. 7.
    Livio, S., Strockbine, N., Panchalingam, S., Tennant, S. M., Barry, E. M., Marohn, M. E., Antonio, M., Hossain, A., Mandomando, I., Ochieng, J., B. Oundo, J. O., Qureshi, S., Ramamurthy, T, Tamboura, B., Adegbola, R. A., Hossain, M. J., Saha, D., Sen, S., Faruque, A. S., Alonso, P. L., Breiman, R. F., Zaidi, A. K., Sur, D., Sow, S. O., Berkeley, L. Y, O’Reilly, C., Mintz, E. D., Biswas, K., Cohen, D., Farag, T H., Nasrin, D., Wu, Y., Blackwelder, W. C., Kotloff, K. L., Nataro, J. P., and Levine, M. M. (2014) Shigella isolates from the Global Enteric Multicenter Study inform vaccine development, Clin. Infect. Dis., 59, 933–941.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Kenne, L., Lindberg, B., Petersson, K., Katzenellenbogen, E., and Romanowska, E. (1978) Structural studies of Shigella flexneri O-antigens, Eur. J. Biochem., 91, 279–284.PubMedCrossRefGoogle Scholar
  9. 9.
    Simmons, D. A. R., and Romanowska, E. (1987) Structure and biology of Shigella flexneri O antigens, J. Med. Microbiol., 23, 289–302.PubMedCrossRefGoogle Scholar
  10. 10.
    Perepelov, A. V., Shekht, M. E., Liu, B., Shevelev, S. D., Ledov, V. A., L’vov, V. L., Senchenkova, S. N., Shashkov, A. S., Feng, L., Aparin, P. G., Wang, L., and Knirel, Y. A. (2012) Shigella flexneri O-antigens revisited: final elucidation of the O-acetylation profiles and a survey of the Oantigen structure diversity, FEMS Immunol. Med. Microbiol., 66, 201–210.PubMedCrossRefGoogle Scholar
  11. 11.
    Liu, B., Knirel, Y. A., Feng, L., Perepelov, A. V., Senchenkova, S. N., Wang, Q., Reeves, P. R., and Wang, L. (2008) Structure and genetics of Shigella O antigens, FEMS Microbiol. Rev., 32, 627–653.PubMedCrossRefGoogle Scholar
  12. 12.
    Li, Y., Cao, B., Liu, B., Liu, D., Gao, Q., Peng, X., Wu, J., Bastin, D. A., Feng, L., and Wang, L. (2009) Molecular detection of all 34 distinct O-antigen forms of Shigella, J. Med. Microbiol., 58, 69–81.PubMedCrossRefGoogle Scholar
  13. 13.
    Perepelov, A. V., Shevelev, S. D., Liu, B., Senchenkova, S. N., Shashkov, A. S., Feng, L., Knirel, Y. A., and Wang, L. (2010) Structures of the O-antigens of Escherichia coli O13, O129 and O135 related to the O-antigens of Shigella flexneri, Carbohydr. Res., 345, 1594–1599.PubMedCrossRefGoogle Scholar
  14. 14.
    Allison, G. E., and Verma, N. K. (2000) Serotype-converting bacteriophages and O-antigen modification in Shigella flexneri, Trends Microbiol., 8, 17–23.PubMedCrossRefGoogle Scholar
  15. 15.
    Sun, Q., Lan, R., Wang, Y., Zhao, A., Zhang, S., Wang, J., Xia, S., Jin, D., Cui, Z., Zhao, H., Li, Z., Ye, C., Jing, H., and Xu, J. (2011) Development of a multiplex PCR assay targeting O-antigen modification genes for molecular serotyping of Shigella flexneri, J. Clin. Microbiol., 49, 3766–3770.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    West, N. P., Sansonetti, P., Mounier, J., Exley, R. M., Parsot, C., Guadagnini, S., Prevost, M. C., Prochnicka-Chalufour, A., Delepierre, M., Tanguy, M., and Tang, C. M. (2005) Optimization of virulence functions through glucosylation of Shigella LPS, Science, 307, 1313–1317.PubMedCrossRefGoogle Scholar
  17. 17.
    Kohler, H., Rodrigues, S. P., and McCormick, B. A. (2002) Shigella flexneri interactions with the basolateral membrane domain of polarized model intestinal epithelium: role of lipopolysaccharide in cell invasion and in activation of the mitogen-activated protein kinase ERK, Infect. Immun., 70, 1150–1158.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Hong, M., and Payne, S. M. (1997) Effect of mutations in Shigella flexneri chromosomal and plasmid-encoded lipopolysaccharide genes on invasion and serum resistance, Mol. Microbiol., 24, 779–791.PubMedCrossRefGoogle Scholar
  19. 19.
    Brahmbhatt, H. N., Lindberg, A. A., and Timmis, K. N. (1992) Shigella lipopolysaccharide: structure, genetics, and vaccine development, Curr. Top. Microbiol. Immunol., 180, 45–64.PubMedGoogle Scholar
  20. 20.
    Kubler-Kielb, J., Vinogradov, E., Chu, C., and Schneerson, R. (2007) O-Acetylation in the O-specific polysaccharide isolated from Shigella flexneri serotype 2a, Carbohydr. Res., 342, 643–647.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Perepelov, A. V., L’vov, V. L., Liu, B., Senchenkova, S. N., Shekht, M. E., Shashkov, A. S., Feng, L., Aparin, P. G., Wang, L., and Knirel, Y. A. (2009) A similarity in the Oacetylation pattern of the O-antigens of Shigella flexneri types 1a, 1b and 2a, Carbohydr. Res., 344, 687–692.PubMedCrossRefGoogle Scholar
  22. 22.
    Wang, J., Knirel, Y A., Lan, R., Senchenkova, S. N., Luo, X., Perepelov, A. V., Wang, Y, Shashkov, A. S., Xu, J., and Sun, Q. (2014) Identification of an O-acyltransferase gene (oacB) that mediates 3- and 4-O-acetylation of rhamnose III in Shigella flexneri O antigens, J. Bacteriol., 196, 15251531.Google Scholar
  23. 23.
    Knirel, Y. A., Luo, X., Wang, J., Senchenkova, S. N., Lan, R., Shpirt, A. M., Du, P., Shashkov, A. S., Xu, J., and Sun, Q. (2014) Genetic and structural identification of an Oacyltransferase gene (oacC) responsible for the 3/4-Oacetylation on rhamnose III in Shigella flexneri serotype 6, BMC Microbiol., 14, 266.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Sun, Q., Knirel, Y. A., Wang, J., Luo, X., Senchenkova, S. N., Lan, R., Shashkov, A. S., and Xu, J. (2014) Serotypeconverting bacteriophage SfII encodes an acyltransferase protein that mediates 6-O-acetylation of GlcNAc in Shigella flexneri O-antigens, conferring on the host a novel O-antigen epitope, J. Bacteriol., 196, 3656–3666.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Jakhetia, R., Marri, A., Stahle, J., Widmalm, G., and Verma, N. K. (2014) Serotype-conversion in Shigella flexneri: identification of a novel bacteriophage, Sf101, from a serotype 7a strain, BMC Genomics, 15, 742.PubMedGoogle Scholar
  26. 26.
    Perepelov, A. V., L’vov, V. L., Liu, B., Senchenkova, S. N., Shekht, M. E., Shashkov, A. S., Feng, L., Aparin, P. G., Wang, L., and Knirel, Y. A. (2009) A new ethanolamine phosphate-containing variant of the O-antigen of Shigella flexneri type 4a, Carbohydr. Res., 344, 1588–1591.PubMedCrossRefGoogle Scholar
  27. 27.
    Sun, Q., Knirel, Y. A., Lan, R., Wang, J., Senchenkova, S. N., Jin, D., Shashkov, A. S., Xia, S., Perepelov, A. V., Chen, Q., Wang, Y, Wang, H., and Xu, J. (2012) A novel plasmidencoded serotype conversion mechanism through addition of phosphoethanolamine to the O-antigen of Shigella flexneri, PLoS ONE, 7, e46095.CrossRefGoogle Scholar
  28. 28.
    Knirel, Y. A., Lan, R., Senchenkova, S. N., Wang, J., Shashkov, A. S., Wang, Y, Perepelov, A. V., Xiong, Y, Xu, J., and Sun, Q. (2013) O-antigen structure of Shigella flexneri serotype Yv and effect of the lpt-O gene variation on phosphoethanolamine modification of S. flexneri O-antigens, Glycobiology, 23, 475–485.PubMedCrossRefGoogle Scholar
  29. 29.
    Sun, Q., Lan, R., Wang, J., Xia, S., Wang, Y, Wang, Y, Jin, D., Yu, B., Knirel, Y. A., and Xu, J. (2013) Identification and characterization of a novel Shigella flexneri serotype Yv in China, PLoS ONE, 8, e70238.CrossRefGoogle Scholar
  30. 30.
    Kenne, L., Lindberg, B., Petersson, K., and Romanowska, E. (1977) Basic structure of the oligosaccharide repeatingunit of the Shigella flexneri O-antigens, Carbohydr. Res., 56, 363–370.PubMedCrossRefGoogle Scholar
  31. 31.
    Carlin, N. I. A., and Lindberg, A. A. (1987) Monoclonal antibodies specific for Shigella flexneri lipopolysaccharides: clones binding to type IV, V, and VI antigens, group 3,4 antigen, and an epitope common to all Shigella flexneri and Shigella dysenteriae type 1 strains, Infect. Immun., 55, 14121420.Google Scholar
  32. 32.
    Carlin, N. I. A., Bundle, D. R., and Lindberg, A. A. (1987) Characterization of five Shigella flexneri variant Y-specific monoclonal antibodies using defined saccharides and glycoconjugate antigens, J. Immunol., 138, 4419–4427.PubMedGoogle Scholar
  33. 33.
    Wang, J., Lan, R., Knirel, Y. A., Luo, X., Senchenkova, S. N., Shashkov, A. S., Xu, J., and Sun, Q. (2014) Serological identification and prevalence of a novel O-antigen epitope linked to 3- and 4-O-acetylated rhamnose III of lipopolysaccharide in Shigella flexneri, J. Clin. Microbiol., 52, 2033–2038.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Shashkov, A. S., Senchenkova, S. N., Sun, Q., Lan, R., Wang, J., Perepelov, A. V, Knirel, Y A., and Xu, J. (2013) Structure of the O-antigen of a novel Shigella flexneri serotype, 1d (I: 7,8), Carbohydr. Res., 373, 93–96.PubMedCrossRefGoogle Scholar
  35. 35.
    Kenne, L., Lindberg, B., Petersson, K., Katzenellenbogen, E., and Romanowska, E. (1977) Structural studies of the Shigella flexneri variant X, type 5a and 5b O-antigens, Eur. J. Biochem., 76, 327–330.PubMedCrossRefGoogle Scholar
  36. 36.
    Dmitriev, B. A., Knirel, Y A., Sheremet, O. K., Shashkov, A. S., Kochetkov, N. K., and Hofman, I. L. (1979) Somatic antigens of Shigella. The structure of the specific polysaccharide of Shigella newcastle (Sh. flexneri type 6) lipopolysaccharide, Eur. J. Biochem., 98, 309–316.PubMedCrossRefGoogle Scholar
  37. 37.
    Wehler, T, and Carlin, N. I. A. (1988) Structural and immunochemical studies of the lipopolysaccharide from a new provisional serotype of Shigella flexneri, Eur. J. Biochem., 176, 471–476.PubMedCrossRefGoogle Scholar
  38. 38.
    Foster, R. A., Carlin, N. I. A., Majcher, M., Tabor, H., Ng, L.-K., and Widmalm, G. (2011) Structural elucidation of the O-antigen of the Shigella flexneri provisional serotype 88-893: structural and serological similarities with Shigella flexneri provisional serotype Y394 (1c), Carbohydr. Res., 346, 872–876.PubMedCrossRefGoogle Scholar
  39. 39.
    Kondakova, A. N., Vinogradov, E. V., Shekht, M. E., Markina, A. A., Lindner, B., L’vov, V. L., Aparin, P. G., and Knirel, Y. A. (2010) Structure of the oligosaccharide region (core) of the lipopolysaccharides of Shigella flexneri types 2a and 5b, Bioorg. Khim., 36, 396–399.Google Scholar
  40. 40.
    Kubler-Kielb, J., Vinogradov, E., Mocca, C., Pozsgay, V., Coxon, B., Robbins, J. B., and Schneerson, R. (2010) Immunochemical studies of Shigella flexneri 2a and 6, and Shigella dysenteriae type 1 O-specific polysaccharide-core fragments and their protein conjugates as vaccine candidates, Carbohydr. Res., 345, 1600–1608.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Guan, S., Bastin, D. A., and Verma, N. K. (1999) Functional analysis of the O antigen glucosylation gene cluster of Shigella flexneri bacteriophage SfX, Microbiology, 145, 1263–1273.PubMedCrossRefGoogle Scholar
  42. 42.
    Carlin, N. I. A., Wehler, T, and Lindberg, A. A. (1986) Shigella flexneri O-antigen epitopes: chemical and immunochemical analyses reveal that epitopes of type III and group 6 antigens are identical, Infect. Immun., 53, 110115.Google Scholar
  43. 43.
    Lugowski, C., Romanowska, E., Kenne, L., and Lindberg, B. (1983) Identification of a trisaccharide repeating-unit in the enterobacterial common-antigen, Carbohydr. Res., 118, 173–181.CrossRefGoogle Scholar
  44. 44.
    Dell, A., Oates, J., Lugowski, C., Romanowska, E., Kenne, L., and Lindberg, B. (1984) The enterobacterial commonantigen, a cyclic polysaccharide, Carbohydr. Res., 133, 95104.CrossRefGoogle Scholar
  45. 45.
    Carlin, N. I., Rahman, M., Sack, D. A., Zaman, A., Kay, B., and Lindberg, A. A. (1989) Use of monoclonal antibodies to type Shigella flexneri in Bangladesh, J. Clin. Microbiol., 27, 1163–1166.PubMedCentralPubMedGoogle Scholar
  46. 46.
    Talukder, K. A., Dutta, D. K., Safa, A., Ansaruzzaman, M., Hassan, F., Alam, K., Islam, K. M., Carlin, N. I., Nair, G. B., and Sack, D. A. (2001) Altering trends in the dominance of Shigella flexneri serotypes and emergence of serologically atypical S. flexneri strains in Dhaka, Bangladesh, J. Clin. Microbiol., 39, 3757–3759.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Rusden, A. D., Stephenson, D. P., and Verma, N. K. (2013) Topological investigation of glucosyltransferase V in Shigella flexneri using the substituted cysteine accessibility method, Biochemistry, 52, 2655–2661.PubMedCrossRefGoogle Scholar
  48. 48.
    Markine-Goriaynoff, N., Gillet, L., Van Etten, J. L., Korres, H., Verma, N., and Vanderplasschen, A. (2004) Glycosyltransferases encoded by viruses, J. Gen. Virol., 85, 2741–2754.PubMedCrossRefGoogle Scholar
  49. 49.
    Mavris, M., Manning, P. A., and Morona, R. (1997) Mechanism of bacteriophage SfII-mediated serotype conversion in Shigella flexneri, Mol. Microbiol., 26, 939–950.PubMedCrossRefGoogle Scholar
  50. 50.
    Allison, G. E., Angeles, D., Tran-Dinh, N., and Verma, N. K. (2002) Complete genomic sequence of SfV, a serotypeconverting temperate bacteriophage of Shigella flexneri, J. Bacteriol., 184, 1974–1987.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Allison, G. E., Angeles, D. C., Huan, P. T, and Verma, N. K. (2003) Morphology of temperate bacteriophage SfV and characterization of the DNA packaging and capsid genes: the structural genes evolved from two different phage families, Virology, 308, 114–127.PubMedCrossRefGoogle Scholar
  52. 52.
    Sun, Q., Lan, R., Wang, Y, Wang, J., Wang, Y, Li, P., Du, P., and Xu, J. (2013) Isolation and genomic characterization of SfI, a serotype-converting bacteriophage of Shigella flexneri, BMC Microbiol., 13, 39.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    George, D. T, Stephenson, D. P., Tran, E., Morona, R., and Verma, N. K. (2013) Complete genome sequence of SfII, a serotype-converting bacteriophage of the highly prevalent Shigella flexneri serotype 2a, Genome Announc., 1, e00626–13.CrossRefGoogle Scholar
  54. 54.
    Jakhetia, R., Talukder, K. A., and Verma, N. K. (2013) Isolation, characterization and comparative genomics of bacteriophage SfIV: a novel serotype converting phage from Shigella flexneri, BMC Genomics, 14, 677.PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Sun, Q., Lan, R., Wang, Y, Wang, J., Luo, X., Zhang, S., Li, P., Wang, Y., Ye, C., Jing, H., and Xu, J. (2011) Genesis of a novel Shigella flexneri serotype by sequential infection of serotype-converting bacteriophages SfX and SfI, BMC Microbiol., 11, 269.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Stagg, R. M., Tang, S. S., Carlin, N. I., Talukder, K. A., Cam, P. D., and Verma, N. K. (2009) A novel glucosyltransferase involved in O-antigen modification of Shigella flexneri serotype 1c, J. Bacteriol., 191, 6612–6617.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Thanweer, F., Tahiliani, V., Korres, H., and Verma, N. K. (2008) Topology and identification of critical residues of the O-acetyltransferase of serotype-converting bacteriophage, SF6, of Shigella flexneri, Biochem. Biophys. Res. Commun., 375, 581–585.PubMedCrossRefGoogle Scholar
  58. 58.
    Casjens, S., Winn-Stapley, D. A., Gilcrease, E. B., Morona, R., Kuhlewein, C., Chua, J. E., Manning, P. A., Inwood, W, and Clark, A. J. (2004) The chromosome of Shigella flexneri bacteriophage Sf6: complete nucleotide sequence, genetic mosaicism, and DNA packaging, J. Mol. Biol., 339, 379–394.PubMedCrossRefGoogle Scholar
  59. 59.
    Sun, Q., Lan, R., Wang, Y., Wang, J., Xia, S., Wang, Y, Zhang, J., Yu, D., Li, Z., Jing, H., and Xu, J. (2012) Identification of a divergent O-acetyltransferase gene oac1b from Shigella flexneri serotype 1b strains, Emerg. Microbes Infect., 1, e21.CrossRefGoogle Scholar
  60. 60.
    Sun, Q., Knirel, Y. A., Lan, R., Wang, J., Senchenkova, S. N., Shashkov, A. S., Wang, Y, Wang, Y, Luo, X., and Xu, J. (2014) Dissemination and serotype modification potential of pSFxv_2, an O-antigen PEtN modification plasmid in Shigella flexneri, Glycobiology, 24, 305–313.PubMedCrossRefGoogle Scholar
  61. 61.
    Zhang, N., Lan, R., Sun, Q., Wang, J., Wang, Y, Zhang, J., Yu, D., Hu, W., Hu, S., Dai, H., Du, P., Wang, H., and Xu, J. (2014) Genomic portrait of the evolution and epidemic spread of a recently emerged multidrug-resistant Shigella flexneri clone in China, J. Clin. Microbiol., 52, 1119–1126.PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Ye, C., Lan, R., Xia, S., Zhang, J., Sun, Q., Zhang, S., Jing, H., Wang, L., Li, Z., Zhou, Z., Zhao, A., Cui, Z., Cao, J., Jin, D., Huang, L., Wang, Y, Luo, X., Bai, X., Wang, P., Xu, Q., and Xu, J. (2010) Emergence of a new multidrug-resistant serotype X variant in an epidemic clone of Shigella flexneri, J. Clin. Microbiol., 48, 419426.Google Scholar
  63. 63.
    Qiu, S., Wang, Z., Chen, C., Liu, N., Jia, L., Liu, W., Wang, L., Hao, R., Zhang, L., Wang, Y, and Song, H. (2011) Emergence of a novel Shigella flexneri serotype 4s strain that evolved from a serotype X variant in China, J. Clin. Microbiol., 49, 1148–1150.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2015

Authors and Affiliations

  1. 1.Zelinsky Institute of Organic ChemistryRussian Academy of SciencesMoscowRussia
  2. 2.State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina

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