Chapter 35 : Respiration and Small-Colony Variants of Staphylococcus aureus

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

Preview this chapter:
Zoom in

Respiration and Small-Colony Variants of Staphylococcus aureus, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816513/9781555813437_Chap35-1.gif /docserver/preview/fulltext/10.1128/9781555816513/9781555813437_Chap35-2.gif


respiration and carbohydrate metabolism follow patterns very similar to those in , with glycolysis in staphylococci following the nearly universal patterns found in all biological systems. Reactions that are favored in respiratory-deficient small-colony variants (SCVs) are shown in a table, and it is apparent that these variants are optimizing reactions that produce ATP and oxidize NADH by non-oxygen-dependent mechanisms. Although mutations in any essential gene can cause slow growth and small colonies, this chapter considers a subset of these mutants that was first observed in patients who had unusually persistent infections and were later found to have defects in oxidative metabolism and electron transport. This chapter focuses on multiple phenotypic changes associated with interrupted electron transport. It was also found that bacterial electron transport inhibitors Z69 and Z90 are able to reproduce the SCV phenotype. JB-1 is a menadione auxotrophic SCV that was selected with gentamicin from its parent, 6850. Some hemin auxotrophs selected by resistance to gentamicin have also been characterized in detail. Although many different mutations might produce slow growth, menadione and hemin auxotrophs predominate among clinical SCV isolates. Finally, the chapter talks about instability of the SCV phenotype, SCVs and antibiotic resistance, and electron transport, respiration, and toxin production in .

Citation: Proctor R. 2006. Respiration and Small-Colony Variants of Staphylococcus aureus, p 434-442. 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.ch35
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Relationship between electron transport and the small-colony variant phenotype in .

Citation: Proctor R. 2006. Respiration and Small-Colony Variants of Staphylococcus aureus, p 434-442. 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.ch35
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Abele-Horn, M.,, B. Schupfner,, P. Emmerling,, H. Waldner,, and H. Goring. 2000. Persistent wound infection after herniotomy associated with small-colony variants of Staphylococcus aureus. Infection 28: 53 54.
2. Baddour, L. M.,, and G. D. Christensen. 1987. Prosthetic valve endocarditis due to small-colony staphylococcal variants. Rev. Infect. Dis. 9: 1168 1174.
3. Baldwin, J. E.,, and H. Krebs. 1981. The evolution of metabolic cycles. Nature 291: 381 382.
4. Balwit, J. M.,, P. van Langevelde,, J. M. Vann,, and R. A. Proctor. 1994. Gentamicin-resistant, menadione and hemin auxotrophic Staphylococcus aureus persist within cultured endothelial cells. J. Infect. Dis. 170: 1033 1037.
5. Barbour, R. G. H. 1950. Small colony variants (“G” forms) produced by Staphylococcus pyogenes during the development of resistance to streptomycin. Aust. J. Exp. Biol. Med. Sci. 28: 411 421.
6. Bates, D.,, C. von Eiff,, G. Peters,, A. Bayer,, and R. A. Proctor. 2003. A menD, but not hemB, mutant persists within the kidney in the rabbit endocarditis model. J. Infect. Dis. 187: 1654 1661.
7. Baumert, N.,, C. von Eiff,, F. Schaaff,, G. Peters,, R. A. Proctor,, and H. G. Sahl. 2002. Physiology and antibiotic susceptibility of Staphylococcus aureus small colony variants. Microb. Drug Resist. 8: 253 260.
8. Bentley, R.,, and R. Meganathan. 1982. Biosynthesis of vitamin K (menaquinone) in bacteria. Microbiol. Rev. 46: 241 280.
9. Bishop, D. H. L.,, K. D. Pandya,, and H. K. King. 1962. Ubiquinone and vitamin K in bacteria. Biochem. J. 83: 606 614.
10. Brown, M. R.,, P. J. Collier,, and P. Gilbert. 1990. Influence of growth rate on susceptibility to antimicrobial agents: modification of the cell envelope and batch and continuous culture studies. Antimicrob. Agents Chemother. 34: 1623 1628.
11. Chinn, B. D. 1936. Characteristics of small colony variants with special reference to Shigella paradysenteriae sonne. J. Infect. Dis. 59: 137 157.
12. Chuard, C.,, P. E. Vaudaux,, R. A. Proctor,, and D. P. Lew. 1997. Decreased susceptibility to antibiotic killing of small colony variants of Staphylococcus aureus in fluid phase and on fibronectin-coated surfaces. J. Antimicrob. Chemother. 39: 603 608.
13. Clements, M. O.,, S. P. Watson,, R. K. Poole,, and S. J. Foster. 1999. CtaA of Staphylococcus aureus is required for starvation survival, recovery, and cytochrome biosynthesis. J. Bacteriol. 181: 501 507.
14. Clerch, B.,, E. Rivera,, and M. Llagostera. 1996. Identification of a pKM101 region which confers a slow growth rate and interferes with susceptibility to quinonolone in Escherichia coli AB1157. J. Bacteriol. 178: 5568 5572.
15. Collins, M. D.,, and D. Jones. 1981. Distribution of isoprenoid quinone structure types in bacteria and their taxonomic implications. Microbiol. Rev. 45: 316 354.
16. Darouiche, R. O.,, and R. J. Hamill. 1994. Antibiotic penetration of and bactericidal activity within endothelial cells. Antimicrob. Agents Chemother. 38: 1059 1064.
17. de la Fuente, R.,, K. H. Schleifer,, F. Götz,, and H.-P. Köst. 1986. Accumulation of porphyrins and pyrrole pigments by Staphylococcus aureus ssp. anaerobius and its aerobic mutant. FEMS Microbiol. Lett. 45: 183 188.
18. Eisenberg, E. S.,, L. J. Mandel,, H. R. Kaback,, and M. H. Miller. 1984. Quantitative association between electrical potential across the cytoplasmic membrane and early gentamicin uptake and killing in Staphylococcus aureus. J. Bacteriol. 157: 863 867.
19. Eisenberg, P. 1910. Untersuchungen über die variablen Typhusstamm ( Bacterium typhi mutabile), sowie über eine eigentumliche hemmende Wirkung des gewöhnlichen Agar, verursacht durch Autoklavierung, abstr. 56. Zentbl. Bakteriol. Abt., 1: 208.
20. Eng, R. H. K.,, F. T. Padberg,, S. M. Smith,, E. N. Tan,, and C. E. Cherubin. 1991. Bactericidal effects of antibiotics on slowly and nongrowing bacteria. Antimicrob. Agents Chemother. 35: 1824 1828.
21. Evans, D. J.,, D. G. Allison,, M. R. W. Brown,, and P. Gilbert. 1991. Susceptibility of Pseudomonas aeruginosa and Escherichia coli biofilms toward ciprofloxacin: effect of specific growth rate. J. Antimicrob. Chemother. 27: 177 184.
22. Fillingame, R. H. 1997. Coupling H + transport and ATP synthesis in F0F1 ATP synthases: glimpses of interacting parts in a dynamic molecular machine. J. Exp. Biol. 200: 217 224.
23. Fillingame, R. H.,, P. C. Jones,, W. Jiang,, F. I. Valiyaveetil,, and O. Y. Dmitriev. 1998. Subunit organization and structure in the F0 sector of Escherichia coli F 0F1 ATP synthase. Biochim. Biophys. Acta 1365: 135 142.
24. Frerman, F. E.,, and D. C. White. 1967. Membrane lipid changes during formation of a functional electron transport system in Staphylococcus aureus. J. Bacteriol. 94: 1868 1874.
25. Gilman, S.,, and V. Saunders. 1986. Accumulation of gentamicin by Staphylococcus aureus: the role of transmembrane electrical potential. J. Antimicrob. Chemother. 17: 37 44.
26. Goldenbaum, P. E.,, and D. C. White. 1974. Role of lipid in the formation and function of the respiratory system of Staphylococcus aureus. Ann. N.Y. Acad. Sci. 236: 115 123.
27. Hale, J. H. 1947. Studies on staphylococcal mutation: characteristics of the “G” (gonidial) variant and factors concerned in its production. Br. J. Exp. Pathol. 28: 202 210.
28. Huang, C. T.,, F. P. Yu,, G. A. McFeters,, and P. S. Stewart. 1995. Nonuniform spatial patterns of respiratory activity within biofilms during disinfection. Appl. Environ. Microbiol. 61: 2252 2256.
29. Jensen, P. R.,, and O. Michelsen. 1992. Carbon and energy metabolism of atp mutants of Escherichia coli. J. Bacteriol. 174: 7635 7641.
30. Jonsson, I.-M.,, C. von Eiff,, R. A. Proctor,, G. Peters,, C. Ryden,, and A. Tarkowski. 2003. Virulence of a hemB mutant Staphylococcus aureus small colony variant in a murine model of septic arthritis. Microbial Pathog. 34: 73 79.
31. Joyce, G. H.,, and D. C. White. 1971. Effect of benso(a) pyrene and piperonyl butoxide on formation of respiratory system, phospholipids, and carotenoids of Staphylococcus aureus. J. Bacteriol. 106: 403 411.
32. Kafala, B.,, and A. Sasarman. 1994. Cloning and sequence analysis of the hemB gene of Staphylococcus aureus. Can. J. Microbiol. 40: 651 657.
33. Kahl, B,, A. Duebbers,, G. Lubritz,, J. Haeberle,, H. G. Koch,, B. Ritzerfeld,, M. Reilly,, E. Harms,, R. A. Proctor,, M. Herrmann,, and G. Peters. 2003. Population dynamics and persistence of Staphylococcus aureus infection in cystic fibrosis patients. J. Clin. Microbiol. 41: 4424 4427.
34. Kahl, B.,, R. A. Proctor,, A. Schulze-Everding,, M. Herrmann,, H. G. Koch,, I. Harms,, and G. Peters. 1998. Persistent infection with small colony variant strains of Staphylococcus aureus in patients with cystic fibrosis. J. Infect. Dis. 177: 1023 1029.
35. Kahl, B.,, C. von Eiff,, M. Herrmann,, G. Peters,, and R. A. Proctor. 1996. Staphylococcal small colony variants present a challenge to clinicians and clinical microbiologists. Antimicrob. Infect. Dis. Newsl. 15: 59 63.
36. Kaplan, M. W.,, and W. E. Dye. 1976. Growth requirements of some small-colony-forming variants of Staphylococcus aureus. J. Clin. Microbiol. 4: 343 348.
37. Kipp, F.,, W. Ziebuhr,, K. Becker,, V. Krimmer,, N. Hobeta,, G. Peters,, and C. von Eiff. 2003. Detection of Staphylococcus aureus by 16S rRNA directed in situ hybridisation in a patient with a brain abscess caused by small colony variants. J. Neurol. Neurosurg. Psychiatry 74: 1000 1002.
38. Kohler, C.,, C. von Eiff,, G. Peters,, R. A. Proctor,, M. Hecker,, and S. Engelmann. 2003. Physiological characterization of a heme-deficient mutant of Staphylococcus aureus by a proteomic approach. J. Bacteriol. 185: 6928 6937.
39. Koo, S. P.,, A. S. Bayer,, H.-G. Sahl,, R. A. Proctor,, and M. R. Yeaman. 1996. Staphylocidal action of thrombin-induced platelet microbicidal protein (tPMP) is not solely dependent on transmembrane potential (Δψ). Infect. Immun. 64: 1070 1074.
40. Lewis, L. A.,, K. Li,, M. Bharosay,, M. Cannella,, V. Jorgenson,, R. Thomas,, D. Pena,, M. Velez,, B. Pereira,, and A. Sassine. 1990. Characterization of gentamicin-resistant respiratory-deficient (Res ) variant strains of Staphylococcus aureus. Microbiol. Immunol. 34: 587 605.
41. Massey, R. C.,, A. Buckling,, and S. J. Peacock. 2001. Phenotypic switching of antibiotic resistance circumvents permanent costs in Staphylococcus aureus. Curr. Biol. 11: 1810 1814.
42. Massey, R. C.,, and S. J. Peacock. 2002. Antibiotic-resistant sub-populations of the pathogenic bacterium Staphylococcus aureus confer population-wide resistance. Curr. Biol. 12: R686 R687.
43. Musher, D. M.,, R. E. Baughn,, G. B. Templeton,, and J. N. Minuth. 1977. Emergence of variant forms of Staphylococcus aureus after exposure to gentamicin and infectivity of the variants in experimental animals. J. Infect. Dis. 136: 360 369.
44. Neumann, S.,, U. Matthey,, G. Kaim,, and P. Dimroth. 1998. Purification and properties of the F 0F1 ATPase of Ilyobacter tartaricus, a sodium ion pump. J. Bacteriol. 180: 3312 3316.
45. Novick, R., 1993. Staphylococcus, p. 17 33. In A. L. Sonenshein,, J. A. Hoch,, and R. Losick (ed.), Bacillus subtilis and Other Gram-Positive Bacteria. American Society for Microbiology, Washington, D.C.
46. Novick, R. P. 2003. Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol. Microbiol. 48: 1429 1449.
47. Nydahl, B. C.,, and W. L. Hall. 1965. The treatment of staphylococcal infection with nafcillin with a discussion of staphylococcal nephritis. Ann. Intern. Med. 63: 27 43.
48. Pan, X. S.,, P. J. Hamlyn,, R. Talens-Visconti,, F. L. Alovero,, R. H. Manzo,, and L. M. Fisher. 2002. Small-colony mutants of Staphylococcus aureus allow selection of gyrase-mediated resistance to dual-target fluoroquinolones. Antimicrob. Agents Chemother. 46: 2498 2506.
49. Proctor, R. A., 1994. Microbial pathogenic factors: small colony variants, p. 77 90. In A. L. Bisno, and F. A. Waldvogel (ed.), Infections Associated with Indwelling Medical Devices, 2nd ed. American Society for Microbiology, Washington, D.C.
50. Proctor, R. A. 1998. Bacterial energetics and antimicrobial resistance. Drug Resist. Updates 1: 227 235.
51. Proctor, R. A.,, D. M. Bates,, and P. J. McNamara,. 2001. Electron transport-deficient Staphylococcus aureus small-colony variants as emerging pathogens, p. 95 110. In W. Craig (ed.), Emerging Infections, vol. 5. ASM Press, Washington, D.C.
52. Proctor, R. A.,, S. Dalal,, B. Kahl,, D. Brar,, G. Peters,, and W. W. Nichols. 2002. Two diarylurea electron transport inhibitors reduce Staphylococcus aureus hemolytic activity and protect cultured endothelial cells from lysis. Antimicrob. Agents Chemother. 46: 2333 2336.
53. Proctor, R. A.,, J. M. Balwit,, and O. Vesga. 1994. Variant subpopulations of Staphylococcus aureus can cause persistent and recurrent infections. Infect. Agents Dis. 3: 302 312.
54. Proctor, R. A.,, and G. Peters. 1998. Small colony variants in staphylococcal infections: diagnostic and therapeutic implications. Clin. Infect. Dis. 27: 419 423.
55. Proctor, R. A.,, P. van Langevelde,, M. Kristjansson,, J. N. Maslow,, and R. D. Arbeit. 1995. Persistent and relapsing infections associated with small colony variants of Staphylococcus aureus. Clin. Infect. Dis. 20: 95 102.
56. Proctor, R. A.,, O. Vesga,, M. F. Otten,, S.-P. Koo,, M. R. Yeaman,, H.-G. Sahl,, and A. S. Bayer. 1996. Staphylococcus aureus small colony variants cause persistent and resistant infections. Chemotherapy (Basel) 42(Suppl. 2): 47 52.
57. Ray, S. C.,, R. Schulick,, D. Flayhart,, and J. Dick. 1997. First report of infection with Staphylococcus aureus subspecies anaerobius, abstr. 567. In Proc. 35th Infect. Dis. Soc. Am. Meet. Infectious Disease Society of America, Alexandria, Va.
58. Regassa, L. B.,, R. P. Novick,, and M. J. Betley. 1992. Glucose and nonmaintained pH decrease expression of the accessory gene regulator ( agr) in Staphylococcus aureus. Infect. Immun. 60: 3381 3388.
59. Reizere, J.,, M. H. Saier, Jr.,, J. Deutscher,, F. Grenier,, J. Thompson,, and W. Hengstenberg. 1988. The phosphoenolpyruvate:sugar phosphotransferase system in gram-positive bacteria: properties, mechanism, and regulation. Crit. Rev. Microbiol. 15: 297 338.
60. Sadowska, B.,, A. Bonar,, C. von Eiff,, R. A. Proctor,, M. Chmiela,, W. Rudnicka,, and B. Rozalska. 2002. Characteristics of Staphylococcus aureus, isolated from airways of cystic fibrosis patients, and their small colony variants. FEMS Immunol. Med. Microbiol. 32: 191 197.
61. Salgado, D. R.,, F. A. Boza,, M. Pinto,, and J. Sampaio. 2001. Outbreak with small colony variants of methicillin-resistant Staphylococcus aureus in an ICU, abstr. K-1226. In Proc. 41st Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, D.C.
62. Santana, M.,, M. S. Ionescu,, A. Vertes,, R. Longin,, F. Kunst,, A. Danchin,, and P. Glaser. 1994. Bacillus subtilis F 0F1 ATPase: DNA sequence of the atp operon and characterization of atp mutants. J. Bacteriol. 176: 6802 6811.
63. Schlievert, P. M.,, J. R. Dringer,, M. H. Kim,, S. J. Projan,, and R. P. Novick. 1992. Effect of glycerol monolaurate on bacterial growth and toxin production. Antimicrob. Agents Chemother. 36: 626 631.
64. Schnitzer, R. J.,, L. J. Camagni,, and M. Buck. 1943. Resistance of small colony variants (G forms) of a staphylococcus toward the bacteriostatic activity of penicillin. Proc. Soc. Exp. Biol. Med. 53: 75 89.
65. Seifert, H.,, C. von Eiff,, and G. Fatkenheuer. 1999. Fatal case due to methicillin-resistant Staphylococcus aureus small colony variants in an AIDS patient. Emerg. Infect. Dis. 5: 450 453.
66. Seifert, H.,, H. Wisplinghoff,, P. Schnabel,, and C. von Eiff. 2003. Small colony variants of Staphylococcus aureus and pacemaker-related infection. Emerg. Infect. Dis. 9: 1316 1318.
67. Silverman, J. A.,, N. G. Perlmutter,, and H. M. Shapiro. 2003. Correlation of daptomycin bactericidal activity and membrane depolarization in Staphylococcus aureus. Antimicrob. Agents Chemother. 47: 2538 2544.
68. Somerville, G. A.,, M. S. Chaussee,, C. I. Morgan,, J. R. Fitzgerald,, D. W. Dorward,, L. J. Reitzer,, and J. M. Musser. 2002. Staphylococcus aureus aconitase inactivation unexpectedly inhibits post-exponential-phase growth and enhances stationary-phase survival. Infect. Immun. 70: 6373 6382.
69. Somerville, G. A.,, B. Said-Salim,, J. M. Wickman,, S. J. Raffel,, B. N. Kreiswirth,, and J. M. Musser. 2003. Correlation of acetate catabolism and growth yield in Staphylococcus aureus: implications for host-pathogen interactions. Infect. Immun. 71: 4724 4732.
70. Spearman, P.,, D. Lakey,, S. Jotte,, A. Chernowitz,, S. Claycomb,, and C. Stratton. 1996. Sternoclavicular joint septic arthritis with small-colony variant Staphylococcus aureus. Diagn. Microbiol. Infect. Dis. 26: 13 15.
71. Taber, H. W., 1993. Respiratory chains, p. 199 212. In A. L. Sonenshein,, J. A. Hoch,, and R. Losick (ed.), Bacillus subtilis and Other Gram-Positive Bacteria. American Society for Microbiology, Washington, D.C.
72. Tien, W.,, and D. C. White. 1968. Linear sequential arrangement of genes for the biosynthetic pathway of heme in Staphylococcus aureus. Proc. Natl. Acad. Sci. USA 61: 1392 1398.
73. Vaudaux, P.,, P. Francois,, C. Bisognano,, W. L. Kelley,, D. P. Lew,, J. Schrenzel,, R. A. Proctor,, P. J. McNamara,, G. Peters,, and C. von Eiff. 2002. Increased expression of clumping factor and fibronectin-binding proteins by small colony variants of Staphylococcus aureus. Infect. Immun. 70: 5428 5437.
74. Vesga, O.,, J. M. Vann,, D. Brar,, and R. A. Proctor. 1996. Staphylococcus aureus small colony variants are induced by the endothelial cell intracellular milieu. J. Infect. Dis. 173: 739 742.
75. von Eiff, C.,, P. McNamara,, D. Bates,, K. Becker,, X. Lei,, M. Ziman,, B. Bochner,, G. Peters,, and R. A. Proctor. Phenotype MicroArray of S. aureus menD and hemB mutants with small colony variant (SCV) phenotype. In Proc. 11th Int. Symp. Staphylococci Staphylococcal Infect., Charleston, S.C.
76. von Eiff, C.,, K. Becker,, D. Metze,, G. Lubritz,, J. Hockmann,, T. Schwarz,, and G. Peters. 2001. Intracellular persistence of Staphylococcus aureus small-colony variants within keratinocytes: a cause for antibiotic treatment failure in a patient with Darier’s disease. Clin. Infect. Dis. 32: 1643 1647.
77. von Eiff, C.,, D. Bettin,, R. A. Proctor,, B. Rolauffs,, N. Lindner,, W. Winkelmann,, and G. Peters. 1997. Recovery of small colony variants of Staphylococcus aureus following gentamicin bead placement for osteomyelitis. Clin. Infect. Dis. 25: 1250 1251.
78. von Eiff, C.,, C. Heilmann,, R. A. Proctor,, C. Woltz,, G. Peters,, and F. Götz. 1997. A site-directed Staphylococcus aureus hemB mutant is a small-colony variant which persists intracellularly. J. Bacteriol. 179: 4706 4712.
79. von Eiff, C.,, P. Vaudaux,, B. C. Kahl,, D. Lew,, S. Emler,, A. Schmidt,, G. Peters,, and R. A. Proctor. 1999. Bloodstream infections caused by small-colony variants of coagulase-negative staphylococci following pacemaker implantation. Clin. Infect. Dis. 29: 932 934.
80. Widmer, A. F.,, A. Wiestner,, R. Frei,, and W. Zimmerli. 1991. Killing of nongrowing and adherent Escherichia coli determines drug efficacy in device-related infections. Antimicrob. Agents Chemother. 35: 741 746.
81. Wise, R. I.,, and W. W. Spink. 1954. The influence of antibiotics on the origin of small colonies (G variants) of Micrococcus pyogenes var. aureus. J. Clin. Invest. 33: 1611 1622.
82. Xu, K.,, J. Delling,, and T. Elliott. 1992. The genes required for heme synthesis in Salmonella typhimurium include those encoding alternative functions for aerobic and anaerobic coproporphyrinogen oxidation. J. Bacteriol. 174: 3953 3963.
83. Youmans, G. P.,, and E. Delves. 1942. The effect of inorganic salts on the production of small colony variants by Staphylococcus aureus. J. Bacteriol. 44: 127 136.


Generic image for table

Redox and ATP-producing reactions in SCVs

Abbreviations: ADH, alcohol dehydrogenase; ArcA = arginine deiminase; ArcB = ornithine transcarbamolyase; ArcC = carbamoylate kinase; CitB = aconitase; FadB = 3-hydroxyacyl-CoA dehydrogenase: HMP, hydroxymonocarboxylic acid phosphatase (flavohemoprotein or pyruvate/nitrite reductase); LDH =lactate dehydrogenase; MltD = mannitol-1-phosphate 5-dehydrogenase; Mqo2 - malate:quinone oxidoreductase; PycA = pyruvate carboxylase; PdhB = pyruvate dehydrogenase El component beta subunit; PflB = pyruvate formate lyase.

SA0182 and SA0224 refer to gene numbers in the N315 genome.

Citation: Proctor R. 2006. Respiration and Small-Colony Variants of Staphylococcus aureus, p 434-442. 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.ch35

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