Chapter 12 : Molecular Epidemiology, Ecology, and Evolution of Group A Streptococci

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Molecular Epidemiology, Ecology, and Evolution of Group A Streptococci, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816513/9781555813437_Chap12-1.gif /docserver/preview/fulltext/10.1128/9781555816513/9781555813437_Chap12-2.gif


Within a bacterial species, there are often strains that differ from another in important biological properties. This is certainly the case for (i.e., group A streptococci; GAS), whose members can cause a wide variety of human diseases, yet there does not appear to exist a single omnipotent strain. To better understand strain differences and their relevance to human disease, stable markers have been identified within organisms of this species. Epidemiological markers are useful for investigating outbreaks of disease, and they can also provide a reference point for deciphering the genetic organization of a bacterial population. The epidemiology of a microbial disease is often, in large part, a reflection of the ecology and evolution of the causative agent. For a bacterial species whose world is largely confined to the human population, the selective pressures that most profoundly shape its genetic structure are intrinsic to the human condition. Local microenvironmental conditions can shift during the course of infection within a single host. Also, ecological conditions can vary widely from host to host, and not all exposed hosts are susceptible to infection by a given strain. From the evolutionary standpoint, invasive disease is a dead end for the infecting GAS organism because the severely ill patient becomes immobilized; thus, opportunities for its transmission to new hosts are diminished.

Citation: Bessen D, Hollingshead S. 2006. Molecular Epidemiology, Ecology, and Evolution of Group A Streptococci, p 143-151. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch12
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Structural features of and -like genes of GAS. Each large box represents an or -like gene, which are arranged in tandem on the chromosome, usually 200 to 300 bp apart. The extent of nucleotide sequence homologies among subregions within and -like genes ranges from highly conserved (open; for regions encoding 5′-end leader peptide and 3′-end cell-associated domains) to highly variable (filled; for regions encoding the determinants of M-serotype). SF forms of the peptidoglycan-spanning coding regions are indicated; five major patterns (A through E) for the content and arrangement of and -like SF gene forms are shown. Other nomenclature that is often used in reference to -like genes includes or (for the SF4 gene), and or (for the downstream -like genes of patterns B through E).

Citation: Bessen D, Hollingshead S. 2006. Molecular Epidemiology, Ecology, and Evolution of Group A Streptococci, p 143-151. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch12
Permissions and Reprints Request Permissions
Download as Powerpoint


2. Beall, B.,, G. Gherardi,, M. Lovgren,, B. Forwick,, R. Facklam,, and G. Tyrrell. 2000. Emm and sof gene sequence variation in relation to serological typing of opacity factor positive group A streptococci. Microbiology 146: 1195 1209.
3. Beres, S. B.,, G. L. Sylva,, K. D. Barbian,, B. Lei,, J. S. Hoff,, N. D. Mammarella,, M. Y. Liu,, J. C. Smoot,, S. F. Porcella,, L. D. Parkins,, D. S. Campbell,, T. M. Smith,, J. K. McCormick,, D. Y. Leung,, P. M. Schlievert,, and J. M. Musser. 2002. Genome sequence of a serotype M3 strain of group A Streptococcus: phage-encoded toxins, the high-virulence phenotype, and clone emergence. Proc. Natl. Acad. Sci. USA 99: 10078 10083.
4. Beres, S. B.,, G. L. Sylva,, D. E. Sturdevant,, C. N. Granville,, M. Y. Liu,, S. M. Ricklefs,, A. R. Whitney,, L.D. Parkins,, N. P. Hoe,, G. J. Adams,, D. E. Low,, F. R. DeLeo,, A. McGeer,, and J. M. Musser. 2004. Genome-wide molecular dissection of serotype M3 group A Streptococcus strains causing two epidemics of invasive infections. Proc. Natl. Acad. Sci. USA 101: 11833 11838.
5. Bessen, D. E.,, and A. Kalia. 2002. Genomic localization of a T-serotype locus to a recombinatorial zone encoding for extracellular matrix-binding proteins in Streptococcus pyogenes. Infect. Immun. 70: 1159 1167.
6. Bessen, D. E.,, C. M. Sotir,, T. L. Readdy,, and S. K. Hollingshead. 1996. Genetic correlates of throat and skin isolates of group A streptococci. J. Infect. Dis. 173: 896 900.
7. Bessen, D. E.,, M. W. Izzo,, E. J. McCabe,, and C. M. Sotir. 1997. Two-domain motif for IgG-binding activity by group A streptococcal emm gene products. Gene 196: 75 82.
8. Bessen, D. E.,, M. W. Izzo,, T. R. Fiorentino,, R. M. Caringal,, S. K. Hollingshead,, and B. Beall. 1999. Genetic linkage of exotoxin alleles and emm gene markers for tissue tropism in group A streptococci. J. Infect. Dis. 179: 627 636.
9. Bessen, D. E.,, J. R. Carapetis,, B. Beall,, R. Katz,, M. Hibble,, B. J. Currie,, T. Collingridge,, M. W. Izzo,, D. A. Scaramuzzino,, and K. S. Sriprakash. 2000. Contrasting molecular epidemiology of group A streptococci causing tropical and non-tropical infections of the skin and throat. J. Infect. Dis. 182: 1109 1116.
10. Bisno, A. L.,, and D. Stevens,. 2000. Streptococcus pyogenes (including streptococcal toxic shock syndrome and necrotizing fasciitis), p. 2101 2117. In G. L. Mandell,, R. G. Douglas,, and R. Dolin (ed.), Principles and Practice of Infectious Diseases, 5th ed., vol. 2. Churchill Livingstone, Philadelphia, Pa.
11. Breese, B. B.,, and C. B. Hall. 1978. Beta Hemolytic Streptococcal Diseases. Houghton Mifflin, Boston, Mass.
12. Carapetis, J.,, D. Gardiner,, B. Currie,, and J. D. Mathews. 1995. Multiple strains of Streptococcus pyogenes in skin sores of Aboriginal Australians. J. Clin. Microbiol. 33: 1471 1472.
13. Cleary, P. P.,, L. McLandsborough,, L. Ikeda,, D. Cue,, J. Krawczak,, and H. Lam. 1998. High-frequency intracellular infection and erythrogenic toxin A expression undergo phase variation in M1 group A streptococci. Mol. Microbiol. 28: 157 167.
14. Cockerill, F. R.,, K. L. MacDonald,, R. L. Thompson,, F. Roberson,, P. C. Kohner,, J. Besser-Wiek,, J. M. Manahan,, J. M. Musser,, P. M. Schlievert,, J. Talbot,, B. Frankfort,, J. M. Steckelberg,, W. R. Wilson,, and M. T. Osterholm. 1997. An outbreak of invasive group A streptococcal disease associated with high carriage rates of the invasive clone among school-aged children. JAMA 277: 38 43.
15. Cohan, F. M. 2002. What are bacterial species? Annu. Rev. Microbiol. 56: 457 487.
16. Davies, H. D.,, A. McGeer,, B. Schwartz,, K. Green,, D. Cann,, A. E. Simor,, and D. E. Low. 1996. Invasive group A streptococcal infections in Ontario, Canada. N. Engl. J. Med. 335: 547 554.
17. Dicuonzo, G.,, G. Gherardi,, G. Lorino,, S. Angeletti,, M. DeCesaris,, E. Fiscarelli,, D. E. Bessen,, and B. Beall. 2001. Group A streptococcal genotypes from pediatric throat isolates in Rome, Italy. J. Clin. Microbiol. 39: 1687 1690.
18. Enright, M. C.,, B. G. Spratt,, A. Kalia,, J. H. Cross,, and D. E. Bessen. 2001. Multilocus sequence typing of Streptococcus pyogenes and the relationship between emm-type and clone. Infect. Immun. 69: 2416 2427.
19. Eriksson, B. K. G.,, A. Villasenor-Sierra,, M. Norgren,, and D. L. Stevens. 2001. Opsonization of T1M1 group A Streptococcus: dynamics of antibody production and strain specificity. Clin. Infect. Dis. 32: E24 E30.
20. Facinelli, B.,, C. Spinaci,, G. Magi,, E. Giovanetti,, and P. E. Varaldo. 2001. Association between erythromycin resistance and ability to enter human respiratory cells in group A streptococci. Lancet 358: 30 33.
21. Facklam, R.,, B. Beall,, A. Efstratiou,, V. Fischetti,, E. Kaplan,, P. Kriz,, M. Lovgren,, D. Martin,, B. Schwartz,, A. Totolian,, D. Bessen,, S. Hollingshead,, F. Rubin,, J. Scott,, and G. Tyrrell. 1999. Report on an international workshop: demonstration of emm typing and validation of provisional M-types of group A streptococci. Emerg. Infect. Dis. 5: 247 253.
22. Falush, D.,, C. Kraft,, N. S. Taylor,, P. Correa,, J. G. Fox,, M. Achtman,, and S. Suerbaum. 2001. Recombination and mutation during long-term gastric colonization by Helicobacter pylori: estimates of clock rates, recombination size, and minimal age. Proc. Natl. Acad. Sci. USA 98: 15056 15061.
23. Feil, E. J.,, E. C. Holmes,, D. E. Bessen,, M.-S. Chan,, N. P. J. Day,, M. C. Enright,, R. Goldstein,, D. Hood,, A. Kalia,, C. E. Moore,, J. Zhou,, and B. G. Spratt. 2001. Recombination within natural populations of pathogenic bacteria: short-term empirical estimates and long-term phylogenetic consequences. Proc. Natl. Acad. Sci. USA 98: 182 187.
24. Fischetti, V. A.,, M. Jarymowycz,, K. F. Jones,, and J. R. Scott. 1986. Streptococcal M protein size mutants occur at high frequency within a single strain. J. Exp. Med. 164: 971 980.
25. Freeman, A. F.,, and S. T. Shulman. 2002. Macrolide resistance in group A Streptococcus. Pediatr. Infect. Dis. J. 21: 1158 1160.
26. Fujita, K.,, K. Murono,, M. Yoshikawa,, and T. Murai. 1994. Decline of erythromycin resistance of group A streptococci in Japan. Pediatr. Infect. Dis. J. 13: 1075 1078.
27. Gardiner, D. L.,, A. M. Goodfellow,, D. R. Martin,, and K. S. Sriprakash. 1998. Group A streptococcal Vir types are M protein gene (emm) sequence type specific. J. Clin. Microbiol. 36: 902 907.
28. Haanes, E. J.,, and P. P. Cleary. 1989. Identification of a divergent M protein gene and an M protein related gene family in serotype 49 Streptococcus pyogenes. J. Bacteriol. 171: 6397 6408.
29. Harbaugh, M. P.,, A. Podbielski,, S. Hugl,, and P. P. Cleary. 1993. Nucleotide substitutions and small-scale insertion produce size and antigenic variation in group A streptococcal M1 protein. Mol. Microbiol. 8: 981 991.
30. Hidalgo-Grass, C.,, M. Ravins,, M. Dan-Goor,, J. Jaffe,, A. E. Moses,, and E. Hanski. 2002. A locus of group A Streptococcus involved in invasive disease and DNA transfer. Mol. Microbiol. 46: 87 99.
31. Hollingshead, S. K.,, V. A. Fischetti,, and J. R. Scott. 1987. Size variation in group A streptococcal M protein is generated by homologous recombination between intragenic repeats. Mol. Gen. Genet. 207: 196 203.
32. Hollingshead, S. K.,, T. L. Readdy,, D. L. Yung,, and D. E. Bessen. 1993. Structural heterogeneity of the emm gene cluster in group A streptococci. Mol. Microbiol. 8: 707 717.
33. Hollingshead, S. K.,, T. Readdy,, J. Arnold,, and D. E. Bessen. 1994. Molecular evolution of a multi-gene family in group A streptococci. Mol. Biol. Evol. 11: 208 219.
34. Horn, D.,, J. Zabriskie,, R. Austrian,, P. Cleary,, J. Ferretti,, V. Fischetti,, E. Gotschlich,, E. Kaplan,, M. McCarty,, S. Opal,, R. Roberts,, A. Tomasz,, and Y. Wachtfogel. 1998. Why have group A streptococci remained susceptible to penicillin? Report on a symposium. Clin. Infect. Dis. 26: 1341 1345.
35. Jeng, A.,, V. Sakota,, Z. Y. Li,, V. Datta,, B. Beall,, and V. Nizet. 2003. Molecular genetic analysis of a group A Streptococcus operon encoding serum opacity factor and a novel fibronectin-binding protein, SfbX. J. Bacteriol. 185: 1208 1217.
36. Johnson, D. R.,, D. L. Stevens,, and E. L. Kaplan. 1992. Epidemiological analysis of group A streptococcal serotypes associated with severe systemic infections, rheumatic fever, or uncomplicated pharyngitis. J. Infect. Dis. 166: 374 382.
37. Johnsson, E.,, A. Thern,, B. Dahlback,, L. O. Heden,, M. Wikstrom,, and G. Lindahl. 1996. A highly variable region in members of the streptococcal M protein family binds the human complement regulator C4BP. J. Immunol. 157: 3021 3029.
38. Jones, K. F.,, S. K. Hollingshead,, J. R. Scott,, and V. A. Fischetti. 1988. Spontaneous M6 protein size mutants of group A streptococci display variation in antigenic and opsonogenic epitopes. Proc. Natl. Acad. Sci. USA 85: 8271 8275.
39. Kaplan, E. L. 1980. The group A streptococcal upper respiratory tract carrier state: an enigma. J. Pediatr. 97: 337 345.
40. Kaplan, E. L.,, and D. R. Johnson. 2001. Unexplained reduced microbiological efficacy of intramuscular benzathine penicillin G and of oral penicillin V in eradication of group A streptococci from children with acute pharyngitis. Pediatrics 108: 1180 1186.
41. Kapur, V.,, S. Kanjilal,, M. R. Hamrick,, L.-L. Li,, T. S. Whittam,, S. A. Sawyer,, and J. M. Musser. 1995. Molecular population genetic analysis of the streptokinase gene of Streptococcus pyogenes mosaic alleles generated by recombination. Mol. Microbiol. 16: 509 519.
42. Kotb, M.,, A. Norrby-Teglund,, A. McGeer,, H. El-Sherbini,, M. T. Dorak,, A. Khurshid,, K. Green,, J. Peeples,, J. Wade,, G. Thomson,, B. Schwartz,, and D. E. Low. 2002. An immunogenetic and molecular basis for differences in outcomes of invasive group A streptococcal infections. Nat. Med. 8: 1398 1404.
43. Lancefield, R. C. 1959. Persistence of type specific antibodies in man following infection with group A streptococci. J. Exp. Med. 110: 271 292.
44. Lancefield, R. C. 1962. Current knowledge of the type specific M antigens of group A streptococci. J. Immunol. 89: 307 313.
45. Leonard, B. A. B.,, M. Woischnik,, and A. Podbielski. 1998. Production of stabilized virulence factor-negative variants by group A streptococci during stationary phase. Infect. Immun. 66: 3841 3847.
46. Levin, B. R. 1996. The evolution and maintenance of virulence in microparasites. Emerg. Infect. Dis. 2: 93 102.
47. Leyden, J. J.,, R. Stewart,, and A. M. Kligman. 1980. Experimental infections with group A streptococci in humans. J. Invest. Dermatol. 75: 196 201.
48. Li, Z. Y.,, V. Sakota,, D. Jackson,, A. R. Franklin,, and B. Beall. 2003. Array of M protein gene subtypes in 1064 recent invasive group A streptococcus isolates recovered from the active bacterial core surveillance. J. Infect. Dis. 188: 1587 1592.
49. Martin, D. R.,, and K. S. Sriprakash. 1996. Epidemiology of group A streptococcal disease in Australia and New Zealand. Rec. Adv. Microbiol. 4: 1 40.
50. Martin, J. M.,, M. Green,, K. A. Barbadora,, and E. R. Wald. 2002. Erythromycin-resistant group A streptococci in schoolchildren in Pittsburgh. N. Engl. J. Med. 346: 1200 1206.
51. Matsumoto, M.,, N. P. Hoe,, M. Y. Liu,, S. B. Beres,, G. L. Sylva,, C. M. Brandt,, G. Haase,, and J. M. Musser. 2003. Intrahost sequence variation in the streptococcal inhibitor of complement gene in patients with human pharyngitis. J. Infect. Dis. 187: 604 612.
52. McGregor, K.,, N. Bilek,, A. Bennett,, A. Kalia,, B. Beall,, J. Carapetis,, B. Currie,, K. Sriprakash,, B. Spratt,, and D. Bessen. 2004. Group A streptococci from a remote community have novel multilocus genotypes but share emm-types and housekeeping alleles. J. Infect. Dis. 189: 717 723.
53. McGregor, K. F.,, B. G. Spratt,, A. Kalia,, A. Bennett,, N. Bilek,, B. Beall,, and D. E. Bessen. 2004. Multi-locus sequence typing of Streptococcus pyogenes representing most known emm-types and distinctions among sub-population genetic structures. J. Bacteriol. 186: 4285 4294.
54. McLandsborough, L. A.,, and P. P. Cleary. 1995. Insertional inactivation of virR in Streptococcus pyogenes M49 demonstrates that VirR functions as a positive regulator of ScpA, FcRA, OF, and M protein. FEMS Microbiol. Lett. 128: 45 52.
55. Moxon, E. R.,, P. B. Rainey,, M. A. Nowak,, and R. E. Lenski. 1994. Adaptive evolution of highly mutable loci in pathogenic bacteria. Curr. Biol. 4: 24 33.
56. Neeman, R.,, N. Keller,, A. Barzilai,, Z. Korenman,, and S. Sela. 1998. Prevalence of internalisation-associated gene, prtF1, among persisting group-A streptococcus strains isolated from asymptomatic carriers. Lancet 352: 1974 1977.
57. Nizet, V.,, B. Beall,, D. J. Bast,, V. Datta,, L. Kilburn,, D. E. Low,, and J. C. De Azavedo. 2000. Genetic locus for streptolysin S production by group A streptococcus. Infect. Immun. 68: 4245 4254.
58. Osterlund, A.,, R. Popa,, T. Nikkila,, A. Scheynius,, and L. Engstrand. 1997. Intracellular reservoir of Streptococcus pyogenes in vivo: a possible explanation for recurrent pharyngotonsillitis. Laryngoscope 107: 640 647.
59. Podbielski, A. 1993. Three different types of organization of the vir regulon in groupAstreptococci. Mol. Gen. Genet. 237: 287 300.
60. Potter, E. V.,, M. Svartman,, I. Mohammed,, R. Cox,, T. Poon-King,, and D. P. Earle. 1978. Tropical acute rheumatic fever and associated streptococcal infections compared with concurrent acute glomerulonephritis. J. Pediatr. 92: 325 333.
61. Prudhomme, M.,, V. Libante,, and J. P. Claverys. 2002. Homologous recombination at the border: insertion-deletions and the trapping of foreign DNA in Streptococcus pneumoniae. Proc. Natl. Acad. Sci. USA 99: 2100 2105.
62. Rakonjac, J. V.,, J. C. Robbins,, and V. A. Fischetti. 1995. DNA sequence of the serum opacity factor of group A streptococci: identification of a fibronectin-binding repeat domain. Infect. Immun. 63: 622 631.
63. Rasmussen, M.,, and L. Bjorck. 2001. Unique regulation of SclB—a novel collagen-like surface protein of Streptococcus pyogenes. Mol. Microbiol. 40: 1427 1438.
64. Reinert, R. R.,, R. Lutticken,, J. A. Sutcliffe,, A. Tait-Kamradt,, M. Y. Cil,, H. M. Schorn,, A. Bryskier,, and A. Al-Lahham. 2004. Clonal relatedness of erythromycin-resistant Streptococcus pyogenes isolates in Germany. Antimicrob. Agents Chemother. 48: 1369 1373.
65. Relf, W. A.,, D. R. Martin,, and K. S. Sriprakash. 1994. Antigenic diversity within a family of M proteins from group A streptococci: evidence for the role of frameshift and compensatory mutations. Gene 144: 25 30.
66. Santagati, M.,, F. Iannelli,, C. Cascone,, F. Campanile,, M. R. Oggioni,, S. Stefani,, and G. Pozziz. 2003. The novel conjugative transposon Tn1207.3 carries the macrolide efflux gene mef(A) in Streptococcus pyogenes. Microb. Drug Resist. 9: 243 247.
67. Schmidt, H.,, and M. Hensel. 2004. Pathogenicity islands in bacterial pathogenesis. Clin. Microbiol. Rev. 17: 14 56.
68. Schneewind, O.,, K. F. Jones,, and V. A. Fischetti. 1990. Sequence and structural characterization of the trypsin-resistant T6 surface protein of group A streptococci . J. Bacteriol. 172: 3310 3317.
69. Seppala, H.,, T. Klaukka,, J. Vuopio-Varkila,, A. Muotiala,, H. Helenius,, K. Lager,, and P. Huovinen. 1997. The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. Finnish Study Group for Antimicrobial Resistance. N. Engl. J. Med. 337: 441 446.
70. Shulman, S. 2004. Group A streptococcal pharyngitis serotype surveillance in North America, 2000-2002. Clin. Infect. Dis. 39: 325 332.
71. Spinaci, C.,, G. Magi,, C. Zampaloni,, L. A. Vitali,, C. Paoletti,, M. R. Catania,, M. Prenna,, L. Ferrante,, S. Ripa,, P. E. Varaldo,, and B. Facinelli. 2004. Genetic diversity of cell-invasive erythromycin-resistant and -susceptible group A streptococci determined by analysis of the RD2 region of the prtF1 gene. J. Clin. Microbiol. 42: 639 644.
72. Stenberg, L.,, P. W. O’Toole,, J. Mestecky,, and G. Lindahl. 1994. Molecular characterization of protein Sir, a streptococcal cell surface protein that binds both immuneglobulin A and immunoglobulin G. J. Biol. Chem. 269: 13458 13464.
73. Svensson, M. D.,, U. Sjöbring,, and D. E. Bessen. 1999. Selective distribution of a high-affinity plasminogen binding site among group A streptococci associated with impetigo. Infect. Immun. 67: 3915 3920.
74. Towers, R. J.,, P. K. Fagan,, S. R. Talay,, B. J. Currie,, K. S. Sriprakash,, M. J. Walker,, and G. S. Chhatwal. 2003. Evolution of sfbI encoding streptococcal fibronectin-binding protein I: horizontal genetic transfer and gene mosaic structure. J. Clin. Microbiol. 41: 5398 5406.
75. Upton, M.,, J. R. Tagg,, P. Wescombe,, and H. F. Jenkinson. 2001. Intra- and interspecies signaling between Streptococcus salivarius and Streptococcus pyogenes mediated by SalA and SalA1 lantibiotic peptides. J. Bacteriol. 183: 3931 3938.
76. VanHeyningen, T.,, T. Fogg,, D. Yates,, E. Hanski,, and M. Caparon. 1993. Adherence and fibronectin-binding are environmentally regulated in the group A streptococcus. Mol. Microbiol. 9: 1213 1222.
76a.. Veasy, L. G.,, L. Y. Tani,, and H. R. Hill. 1994. Persistence of acute rheumatic fever in the intermountain area of the United States. J. Pediatr. 124: 9 16.
77. Viscidi, R. P.,, and J. C. Demma. 2003. Genetic diversity of Neisseria gonorrhoeae housekeeping genes. J. Clin. Microbiol. 41: 197 204.
78. Wannamaker, L. W. 1970. Differences between streptococcal infections of the throat and of the skin. N. Engl. J. Med. 282: 23 31.
79. Wessels, M. R.,, and M. S. Bronze. 1994. Critical role of the group A streptococcal capsule in pharyngeal colonization and infection in mice. Proc. Natl. Acad. Sci. USA 91: 12238 12242.
80. Whatmore, A. M.,, V. Kapur,, D. J. Sullivan,, J. M. Musser,, and M. A. Kehoe. 1994. Non-congruent relationships between variation in emm gene sequences and the population genetic structure of group A streptococci. Molec. Microbiol. 14: 619 631.
81. York, M. K.,, L. Gibbs,, F. Perdreau-Remington,, and G. F. Brooks. 1999. Characterization of antimicrobial resistance in Streptococcus pyogenes isolates from the San Francisco Bay area of northern California. J. Clin. Microbiol. 37: 1727 1731.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error