6 : Electron Transport-Deficient Staphylococcus aureus Small-Colony Variants as Emerging Pathogens

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

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

Electron Transport-Deficient Staphylococcus aureus Small-Colony Variants as Emerging Pathogens, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816988/9781555812164_Chap06-1.gif /docserver/preview/fulltext/10.1128/9781555816988/9781555812164_Chap06-2.gif


A pathogenic organism can be seen as an ‘‘emerging’’ pathogen in several ways. It may be a newly discovered organism, an organism that has acquired new virulence factors or antibiotic resistance, or a well-known pathogen for which newly discovered subpopulations of the parent strain are able to produce disease. small-colony variants (SCVs) fall into the last category. In SCVs, reversal of the SCV phenotype by adding compounds that can be utilized to repair the defect in electron transport simultaneously or by complementing the genetic defect in trans enhances alpha-toxin production. Well-characterized hemin biosynthetic mutants demonstrate an SCV phenotype, including decreased coagulase activity, aminoglycoside resistance, decreased pigmentation, slow growth, and reduced hemolytic activity. Anaerobic growth downregulates menaquinone biosynthesis in and electron transport. Taken together, these observations show that alpha-toxin production is dependent upon electron transport. Carotenoid pigments that give SCV colonies their characteristic yellow color require ATP for their biosynthesis. Aminoglycoside uptake by is an energy-dependent process that requires ATP and an electrochemical gradient, which is produced via the electron transport system.

Citation: Proctor R, Bates D, McNamara P. 2001. Electron Transport-Deficient Staphylococcus aureus Small-Colony Variants as Emerging Pathogens, p 95-110. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 5. ASM Press, Washington, DC. doi: 10.1128/9781555816988.ch6

Key Concept Ranking

Toxic Shock Syndrome Toxin 1
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

Relationship between electron transport and SCV phenotype in . Clinical SCV isolates are frequently found to grow more rapidly when supplemented with thiamine, menadione, or hemin. Each of these substances is a component of the quinone or the cytochromes that constitute part of the electron transport chain. Intact electron transport provides ATP through the biosynthetic enzyme, the FF ATPase; creates an electrochemical gradient across the cell membrane; and is involved in carotenoid biosynthesis. Interruption of electron transport because of the loss of one of the components in the chain or due to anaerobic growth causes multiple phenotypic changes. The organisms grow slowly, have reduced pigmentation, and are more resistant to antibiotics. Cell wall-active antibiotics are less effective because of the low rate of bacterial growth. The smaller negative membrane charge in bacteria deficient in electron transport results in decreased binding of positively charged antibiotics to the membrane. FADH, reduced flavin adenine dinucleotide.

Citation: Proctor R, Bates D, McNamara P. 2001. Electron Transport-Deficient Staphylococcus aureus Small-Colony Variants as Emerging Pathogens, p 95-110. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 5. ASM Press, Washington, DC. doi: 10.1128/9781555816988.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Hypothetical model for regulation of virulence factors in . This is a schematic representation of several signaling factors that have been proposed to regulate staphylococcal virulence factor production. The sensor portions of the two-component regulators (SaeS, ResE, and AgrC) are shown as transmembrane proteins. The cognate response regulators (SaeR, ResD, and AgrA) are thought to be activated (phosphorylated) by the sensor proteins when stimulated. Solid arrows represent positive actions, whereas dashed arrows indicate negative signaling. The locus (accessory gene regulator) was the first reported global regulator of staphylococcal toxins. The operon includes a protein that is processed and released from the bacteria as an autoregulatory cyclic thiolactone peptide. RNAIII is the message from , and it has a dual role. When translated, δ-hemolysin is produced. However, when nontranscribed, RNAIII is an effector molecule that is involved in the regulation of a number of genes involved in the production of virulence factors. Sar (staphylococcal accessory regulator) was subsequently identified and found to positively regulate Agr. SaeRS ( extracellular protein regulator) has recently been identified, and both its positive and negative actions are thought to act after RNAIII. Other protein regulators include Rot, Rlp, Sar, SarR, and SarH1. σ is a stress sigma factor that has negative regulatory effects on Sar. The activity of σ increases as ATP levels drop, thereby giving it a connection to electron transport. ResDE homologues have been identified in , but their precise role in regulating exoprotein production is still undefined; therefore, a question mark is placed by this arrow.

Citation: Proctor R, Bates D, McNamara P. 2001. Electron Transport-Deficient Staphylococcus aureus Small-Colony Variants as Emerging Pathogens, p 95-110. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 5. ASM Press, Washington, DC. doi: 10.1128/9781555816988.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Acar, J. F.,, F. N. Goldstein,, and P. Lagrange. 1978. Human infections caused by thiamine- or menadione-requiring Staphylococcus aureus. J. Clin. Microbiol. 8:142147.
2. Arizono, T.,, M. Oga,, and Y. Sugioka. 1992. Increased resistance of bacteria after adherence to polymethyl methacrylate. An in vitro study. Acta Orthop. Scand. 63:661664.
3. Baddour, L. M.,, G. D. Christensen,, J. H. Lowrance,, and W. A. Simpson. 1989. Pathogenesis of experimental endocarditis. Rev. Infect. Dis. 11:452463.
4. Baddour, L. M.,, W. A. Simpson,, J. J. Weems, Jr.,, M. M. Hill,, and G. D. Christensen. 1988. Phenotypic selection of small-colony variant forms of Staphylococcus epidermidis in the rat model of endocarditis. J. Infect. Dis. 157:757763.
5. Balwit, J. M. 1992. Intracellular Persistence of a Staphylococcus aureus Small-Colony Variant. M.S. thesis. University of Wisconsin, Madison.
6. 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. 170:10331037.
7. 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. 28:411420.
8. Bayer, A. S.,, D. C. Norman,, and K. S. Kim. 1987. Characterization of Pseudomonas aeruginosa isolated during unsuccessful therapy of experimental endocarditis. Antimicrob. Agents Chemother. 31:7075.
9. Bentley, R.,, and R. Meganathan. 1982. Biosynthesis of vitamin K (menaquinone) in bacteria. Microbiol. Rev. 46:241280.
10. Bisno, A. L., 1989. Infections of central nervous system shunts, p. 93109. In A. L. Bisno, and F. A. Waldvogel (ed.), Infections Associated with Indwelling Medical Devices. American Society for Microbiology, Washington, D.C.
11. Borderon, E.,, and T. Horodniceanu. 1976. Mutants déficients à colonies naines de Staphylococcus: étude de trois souches isolées chez des malades porteurs d’ostéosynthèses. Ann. Microbiol. Inst. Pasteur 127A:503514.
12. Borgna-Pignatti, C.,, P. Marradi,, L. Pinelli,, N. Monetti,, and C. Patrini. 1989. Thiamine-responsive anemia in DIDMOAD syndrome. J. Pediatr. 114:405410.
13. 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. 34:16231628.
14. Browning, C. H.,, and H. S. Adamson. 1950. Stable dwarf-colony forms produced by Staphylococcus pyogenes. J. Pathol. Bacteriol. 62:499500.
15. Bryan, L. E.,, and H. M. van den Elzen. 1977. Effects of membrane-energy mutations and cations on streptomycin and gentamicin accumulation by bacteria: a model for entry of streptomycin and gentamicin in susceptible and resistant bacteria. Antimicrob. Agents Chemother. 12:163177.
16. Bryan, L. E.,, and S. Kwan. 1981. Aminoglycoside-resistant mutants of Pseudomonas aeruginosa deficient in cytochrome d, nitrate reductase, and aerobic transport. Antimicrob. Agents Chemother. 19:958964.
17. Bulger, R. J. 1967. A methicillin-resistant strain of Staphylococcus aureus. Clinical and laboratory experience. Ann. Intern. Med. 67:8189.
18. Chambers, H. F.,, and M. M. Miller. 1987. Emergence of resistance to cephalothin and gentamicin during combination therapy for methicillin-resistant Staphylococcus aureus endocarditis in rabbits. J. Infect. Dis. 155:581585.
19. Chien, Y.,, A. C. Manna,, S. J. Projan,, and A. L. Cheung. 1999. SarA, a global regulator of virulence determinants in Staphylococcus aureus, binds to a conserved motif essential for sar-dependent gene regulation. J. Biol. Chem. 274:3716937176.
20. Chin, Y. M.,, and S. A. Harmon. 1971. Genetic studies of kanamycin resistance in Staphylococcus aureus. Jpn. J. Microbiol. 15:417423.
21. Chinn, B. D. 1936. Characteristics of small colony variants with special reference to Shigella paradysenteriae sonne. J. Infect. Dis. 59:137151.
22. Chinn, B. D. 1936. Characteristics of small colony variants of Shigella paradysenteriae sonne and Staphylococcus aureus. Proc. Soc. Exp. Biol. Med. 34:237238.
23. Chuard, C.,, M. Herrmann,, P. Vaudaux,, F. A. Waldvogel,, and D. P. Lew. 1991. Successful therapy of experimental chronic foreign-body infection due to methicillin-resistant Staphylococcus aureus by antimicrobial combinations. Antimicrob. Agents Chemother. 35:26112616.
24. Chuard, C.,, P. E. Vaudaux,, R. A. Proctor,, and D. P. Lew. 1997. Decreased susceptibility to antibiotic killing of a stable small colony variant of Staphylococcus aureus in fluid phase and on fibronectin-coated surfaces. J. Antimicrob. Chemother. 39:603608.
25. Chuard, C.,, P. Vaudaux,, F. A. Waldvogel,, and D. P. Lew. 1993. Susceptibility of Staphylococcus aureus growing on fibronectin-coated surfaces to bactericidal antibiotics. Antimicrob. Agents Chemother. 37:625632.
26. 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. 181:501507.
27. Colien, F. E. 1935. A study of microbic variation in a yellow pigment-producing coccus. J. Bacteriol. 30:301321.
28. Colwell, C. A. 1946. Small colony variants of Escherichia coli. J. Bacteriol. 52:417422.
29. Devriese, L. A. 1973. Hemin-dependent mutants isolated from methicillin-resistant Staphylococcus aureus strains. Antonie Leeuwenhoek J. Microbiol. Serol. 39:3340.
30. Dietz, A. S.,, L. J. Albright,, and T. Tuominen. 1976. Heterotrophic activities of bacterioneuston and bacterioplankton. Can. J. Microbiol. 22:16991709.
31. Dworkin, R.,, G. Modin,, S. Kunz,, O. Rich,, O. Zak,, and M. Sande. 1990. Comparative efficacies of ciprofloxacin, pefloxacin, and vancomycin in combination with rifampin in a rat model of methicillin-resistant Staphylococcus aureus chronic osteomyelitis. Antimicrob. Agents Chemother. 34:10141016.
32. 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. 27:177184.
33. Fournier, B.,, and D. C. Hooper. 2000. A new two-component regulatory system involved in adhesion, autolysis, and extracellular proteolytic activity of Staphylococcus aureus. J. Bacteriol. 182:39553964.
34. Fournier, B.,, and D. C. Hooper. 2000. Expression of the multidrug resistance transporter NorA from Staphylococcus aureus is modified by a two-component regulatory system. J. Bacteriol. 182:664671.
35. Fujiswara, S.,, Y. Miyake,, T. Usui,, and H. Suginaka. 1998. Effect of adherence on antimicrobial susceptibility of Pseudomonas aeruginosa, Serratia marcescens, and Proteus mirabilis. Hiroshima J. Med. Sci. 47:15.
36. Giraudo, A. T.,, A. Calzolari,, A. A. Cataldi,, C. Bogni,, and R. Nagel. 1999. The sae locus of Staphylococcus aureus encodes a two-component regulatory system. FEMS Microbiol. Lett. 177:1522.
37. Giraudo, A. T.,, A. L. Cheung,, and R. Nagel. 1997. The sae locus of Staphylococcus aureus controls exoprotein synthesis at the transcriptional level. Arch. Microbiol. 168:5358.
38. Giraudo, A. T.,, H. Rampone,, A. Calzolari,, and R. Nagel. 1996. Phenotypic characterization and virulence of a sae agr mutant of Staphylococcus aureus. Can. J. Microbiol. 42:120123.
39. Goudie, J. G.,, and R. B. Goudie. 1955. Recurrent infection by a stable dwarf-colony variant of Staphylococcus aureus. J. Clin. Pathol. 8:284287.
40. Hadley, P.,, and H. Carapetian. 1933. A study of the infective qualities possessed by G phase pleomorphism and filterability. J. Bacteriol. 25:9496.
41. Hale, J. H. 1947. Studies on staphylococcal mutation: characterization of the “G” (gonidial) variant and factors concerned in its production. Br. J. Exp. Pathol. 28:202210.
42. Hale, J. H. 1951. Studies on Staphylococcus mutation: a naturally occurring “G” gonidial variant and its carbon dioxide requirements. Br. J. Exp. Pathol. 32:307313.
43. Haung, 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. 61:22522256.
44. Henry, N. K.,, M. S. Rouse,, A. L. Whitesell,, M. E. McConnell, andW. R.Wilson. 1987. Treatment of methicillin-resistant Staphylococcus aureus experimental osteomyelitis with ciprofloxacin or vancomycin alone or in combination with rifampin. Am. J. Med. 82(Suppl. 4A):7375. V
45. Hoffstadt, R. E.,, and G. P. Youmans. 1932. Staphylococcus aureus: dissociation and its relation to infection and to immunity. J. Infect. Dis. 51:216242.
46. Huddleson, I. F.,, and B. Baltzer. 1952. The characteristics and dissociation pattern of type G (micro-colony type) of Brucella abortus, p. 6483. In Studies in Brucellosis III. A series of Five Papers. Department of Bacteriology and Public Health, Michigan State College Agriculture Experiment Station, East Lansing.
47. Jensen, J. 1957. Biosynthesis of hematin compounds in a hemin requiring strain of Micrococcus pyogenes var. aureus. I. The significance of coenzyme A for the terminal synthesis of catalase. J. Bacteriol. 73:324333.
48. Joyce, G. H.,, and D. C. White. 1971. Effects of benzo(a)pyrene and piperonyl butoxide on formation of respiratory system, phospholipids, and carotenoids of Staphylococcus aureus. J. Bacteriol. 106:403411.
49. Kahl, B.,, R. A. Proctor,, and G. Peters. 1996. Staphylococcal small colony variants present a challenge to clinicians and clinical microbiologists. Antimicrob. Infect. Dis. Newsl. 15:5963.
50. 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. 177:10231029.
51. Kaplan, M. L.,, and W. E. Dye. 1976. Growth requirements of some small-colony-forming variants of Staphylococcus aureus. J. Clin. Microbiol. 4:343348.
52. Kolle, W.,, and H. Hetsch. 1911. Die experimentelle Bacteriologie und die Infectionskrankheiten mit besonderer Berücksichtigung der Immunitätslehre, 3rd ed., vol. 1. Urban und Schwarzenberg, Berlin, Germany.
53. Koneman, E. W.,, S. D. Allen,, V. R. Dowell, Jr.,, and H. M. Sommers. 1979. Color Atlas and Textbook of Diagnostic Microbiology, 2nd ed., p. 264265. J. B. Lippincott, Philadelphia, Pa.
54. 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. 64:10701074.
55. Kopeleff, N. 1934. Dissociation and filtration of Lactobacillus acidophilus. J. Infect. Dis. 55:368389.
56. Kullik, I.,, P. Giachino,, and T. Fuchs. 1998. Deletion of the alternative sigma factor σB, in Staphylococcus aureus reveals its function as a global regulator of virulence genes. J. Bacteriol. 180:48144820.
57. Lacy, R. W. 1969. Dwarf-colony variants of Staphylococcus aureus resistant to aminoglycoside antibiotics and to a fatty acid. J. Med. Microbiol. 2:187197.
58. Lacy, R. W.,, and A. A. B. Mitchell. 1969. Gentamicin-resistant Staphylococcus aureus. Lancet ii:14251426.
59. 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. 34:587605.
60. Li, K.,, J. J. Farmer III,, and A. Coppola. 1974. A novel type of resistant bacteria induced by gentamicin. Trans. N. Y. Acad. Sci. 36:396415.
61. Manna, A.,, and A. Cheung. 2001. Characterization of sarR, a modulator of sar expression in Staphylococcus aureus. Infect. Immun. 69:885896.
62. McCabe, K.,, M. D. Mann,, and M. D. Bowie. 1998. D-Lactate production and [14C]succinic acid uptake by adherent and nonadherent Escherichia coli. Infect. Immun. 66:907911.
63. McNamara, P. J.,, K. C. Milligan-Monroe,, S. Khalili,, and R. A. Proctor. 2000. Identification, cloning, and initial characterization of rot, a locus encoding a repressor of extracellular toxins in Staphylococcus aureus. J. Bacteriol 182:31973203.
64. McNamara, P. J.,, K. C. Milligan-Monroe,, D. Bates,, and R. A. Proctor. The isolation and characterization of rlp, a gene encoding a virulence factor gene regulator in Staphylococcus aureus. Mol. Microbiol., in press.
65. Miller, M. H.,, S. C. Edberg,, L. J. Mandel,, C. F. Behar,, and N. H. Steigbigel. 1980. Gentamicin uptake in wild-type and aminoglycoside-resistant small-colony mutants of Staphylococcus aureus. Antimicrob. Agents Chemother. 18:722729.
66. Miller, M. H.,, M. A. Wexler,, and N. H. Steigbigel. 1978. Single and combination antibiotic therapy of Staphylococcus aureus experimental endocarditis: emergence of gentamicin mutants. Antimicrob. Agents Chemother. 14:336343.
67. Morton, H. E.,, and J. Shoemaker. 1945. The identification of Neisseria gonorrhoeae by means of bacterial variation and the detection of small colony forms in clinical material. J. Bacteriol. 50:585590.
68. 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. 136:360369.
69. Novick, R. P.,, and T. W. Muir. 1999. Virulence gene regulation by peptides in staphylococci and other Gram-positive bacteria. Curr. Opin. Microbiol. 2:4045.
70. Nydahl, B. C.,, and W. L. Hall. 1965. The treatment of staphylococcal infection with nafcillin with a discussion of staphylococcal nephritis. Ann. Intern. Med. 63:2743.
71. Padmanaban, G.,, V. Venkateswar,, and P. N. Rangarajan. 1989. Haem as a multifunctional regulator. Trends Biochem. Sci. 14:492496.
72. Pelletier, L. L., Jr.,, M. Richardson,, and M. Feist. 1979. Virulent gentamicin-induced small colony variants of Staphylococcus aureus. J. Lab. Clin. Med. 94:324334.
73. Proctor, R. A. 1998. Bacterial energetics and antimicrobial resistance. Drug Resist. Updates 1:227235.
74. Proctor, R. A., Respiration and small-colony variants of Staphylococcus aureus, p. 345350. In V. A. Fischetti,, R. P. Novick,, J. J. Ferretti,, D. A. Portnoy,, and J. I. Rood (ed.), Gram-Positive Pathogens. ASM Press, Washington, D.C.
75. Proctor, R. A.,, J. M. Balwit,, and O. Vesga. 1994. Variant subpopulations of Staphylococcus aureus as cause of persistent and recurrent infections. Infect. Agents. Dis. 3:302312.
76. Proctor, R. A.,, and G. Peters. 1998. Small colony variants in staphylococcal infections: diagnostic and therapeutic implications. Clin. Infect. Dis. 27:419423.
77. Proctor, R. A.,, B. Kahl,, C. B. von Eiff,, P. E. Vaudaux,, D. P. Lew,, and G. Peters. 1998. Staphylococcal small colony variants have novel mechanisms for antibiotic resistance. Clin. Infect. Dis. 27(Suppl. 1):S68S74.
78. 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. 20:95102.
79. 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 42(Suppl. 2):4752.
80. Quie, P. G. 1969. Microcolonies (G variants) of Staphylococcus aureus. Yale J. Biol. Med. 41: 394403.
81. Sasarman, A.,, K. E. Sanderson,, M. Surdeanu,, and S. Sonea. 1970. Hemin-deficient mutants of Salmonella typhimurium. J. Bacteriol. 102:531536.
82. Sasarman, A.,, M. Surdeanu,, V. Portelance,, R. Dobardzic,, and S. Sorrea. 1971. Classification of vitamin K-deficient mutants of Staphylococcus aureus. J. Gen. Microbiol. 65:125130.
83. Sasarman, A.,, M. Surdeanu,, J. Sabados,, V. Greceanu,, and T. Horodniceanu. 1968. Menaphthone requiring mutants of Staphylococcus aureus. Rev. Can. Biol. 23:333340.
84. Sasarman, A.,, and T. Horodniceanu. 1967. Locus determining normal colony formation on the chromosome of Escherichia coli K12. J. Bacteriol. 94:12681269.
85. Schierholz, J. M.,, J. Beuth,, and B. Pulverer. 1999. Adherent bacteria and activity of antibiotics. J. Antimicrob. Chemother. 43:158160.
86. Schnitzer, R. J.,, L. J. Canagni,, and M. Back. 1943. Resistance of small colony variants (G forms) of a Staphylococcus toward the bacteriostatic activity of penicillin. Proc. Soc. Exp. Biol. Med. 53:7578.
87. Schwank, S.,, A. Rajacic,, W. Zimmerli,, and J. Blaser. 1998. Impact of bacterial biofilm formation on in vitro and in vivo activities of antibiotics. Antimicrob. Agents Chemother. 42:895898.
88. Seifert, H.,, C. von Eiff,, and G. Fätkenheuer. 1999. Fatal case due to methicillin-resistant Staphylococcus aureus small colony variants in an AIDS patient. Emerg. Infect. Dis. 5:450452.
89. Shearer, M. J.,, P. T. McCarthy,, O. E. Crampton,, and M. B. Mattock,. 1987. The assessment of human vitamin K status from tissue measurements, p. 437452. In J. W. Suttie (ed.), Current Advances in Vitamin K Research. Elsevier, New York, N.Y.
90. Sherris, J. C. 1952. Two small colony variants of Staphylococcus aureus isolated in pure culture from closed infected lesions and their carbon dioxide requirements. J. Clin. Pathol. 5:354355.
91. Short, S. A.,, D. C. White,, and H. R. Kaback. 1972. Active transport in isolated bacterial membrane vesicles. V. The transport of amino acids by membrane vesicles prepared from Staphylococcus aureus. J. Biol. Chem. 247:298304.
92. Slifkin, M.,, L. P. Merkow,, S. A. Kreuzberger,, C. Engwall,, and M. Pardo. 1971. Characterization of CO2 dependent microcolony variants of Staphylococcus aureus. Am. J. Clin. Pathol. 56:584592.
93. Sompolinsky, D.,, M. Cohen,, and G. Ziv. 1974. Epidemiological studies on thiamine-less dwarf-colony variants of Staphylococcus aureus as etiologic agents of bovine mastitis. Infect. Immun. 9:217228.
94. Sompolinsky, D.,, Z. E. Geller,, and S. Segal. 1967. Metabolic disorders in thiamine-less dwarf strains of Staphylococcus aureus. J. Gen. Microbiol. 48:205213.
95. Spagna, V. A.,, R. J. Fass,, R. B. Prior,, and T. G. Slama. 1978. Report of a case of bacterial sepsis caused by a naturally occurring variant form of Staphylococcus aureus. J. Infect. Dis. 138:277278.
96. Swingle, E. L. 1934. Studies on small colony variants of Staphylococcus aureus. Proc. Soc. Exp. Biol. Med. 31:891893.
97. Swingle, E. L. 1935. Studies on small colony variants of Staphylococcus aureus. J. Bacteriol. 29:467490.
98. Tegmark, K.,, A. Karlsson,, and S. Arvidson. 2000. Identification and characterization of SarH1, a new global regulator of virulence gene expression in Staphylococcus aureus. Mol. Microbiol. 37:398409.
99. Thomas, M. E. M.,, and J. H. Cowlard. 1955. Studies on a CO2-dependent Staphylococcus. J. Clin. Pathol. 8:288291.
100. Throup, J. P.,, F. Zappacosta,, R. D. Lunsford,, R. S. Annan,, S. A. Carr,, J. T. Lonsdale,, A. P. Bryant,, D. McDevitt,, M. Rosenberg,, and M. K. R. Burnham. The srhSR gene pair from Staphylococcus aureus: genomic and proteomic approaches to the identification and characterization of gene function. Biochemistry, in press.
101. Tien, W.,, and D. C. White. 1968. Linear sequential arrangement of genes for the biosynthetic pathway of protoheme in Staphylococcus aureus. Proc. Natl. Acad. Sci. USA 61:13921398.
102. Vann, J. M.,, and R. A. Proctor. 1988. Cytotoxic effects of ingested Staphylococcus aureus on bovine endothelial cells: role of S. aureus alpha-hemolysin. Microb. Pathog. 4:443453.
103. Vergères, P.,, and J. Blaser. 1992. Amikacin, ceftazidime, and flucloxacillin against suspended and adherent Pseudomonas aeruginosa and Staphylococcus epidermidis in an in vitro model of infection. J. Infect. Dis. 165:281289.
104. Vesga, O.,, M. C. Groeschel,, M. F. Otten,, D. W. Brar,, J. M. Vann,, and R. A. Proctor. 1996. Staphylococcus aureus small colony variants are induced by the endothelial cell intracellular milieu. J. Infect. Dis. 173:739742.
105. 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. 25:12501251.
106. 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. 179:47064712.
107. von Eiff, C.,, N. Lindner,, R. A. Proctor,, W. Winkelmann,, and G. Peters. 1998. Isolation of small colony variants of Staphylococcus aureus following gentamicin bead placement for osteomyelitis as a possible cause for recurrence. Z. Orthop. Grenzgeb. 136:268271. (In German.)
108. von Eiff, C.,, P. Vaudaux,, B. Kahl,, D. P. 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 placements. Clin. Infect. Dis. 29:932934.
109. Weinberg, E. D. 1950. Vitamin requirements of dwarf colony variants of bacteria. J. Infect. Dis. 87:299306.
110. Widmer, A. F.,, A. Wiestner,, R. Frei, andW. Zimmerli. 1991. Killing of nongrowing and adherent Escherichia coli determines drug efficacy in device-related infections. Antimicrob. Agents Chemother. 35:741746.
111. Wilson, S. G.,, and C. C. Sanders. 1976. Selection and characterization of strains of Staphylococcus aureus displaying unusual resistance to aminoglycosides. Antimicrob. Agents Chemother. 10:519525.
112. Wise, R. I. 1956. Small colonies (G variants) of staphylococci: isolation from cultures and infections. Ann. N. Y. Acad. Sci. 65:169174.
113. Wise, R. I.,, and W. W. Spink. 1954. The influence of antibiotics on the origin of small colony (G variants) of Micrococcus pyogenes var. aureus. J. Clin. Investig. 33:16111622.
114. Yarwood, J. M.,, J. K. McCormick,, and P. M. Schlievert. 2001. Identification of a novel two-component regulatory system that acts in global regulation of virulence factors of Staphylococcus aureus. J. Bacteriol. 183:11131123.
115. Yegian, D.,, G. Gallo,, and M. W. Toll. 1959. Kanamycin-resistant staphylococcus mutants requiring hemin for growth. J. Bacteriol. 78:1012.
116. Youmans, G. P. 1937. Production of small colony variants of Staphylococcus aureus. Proc. Soc. Exp. Biol. Med. 36:9498.
117. Youmans, G. P.,, and E. Delves. 1942. The effect of inorganic salts on the production of small colony variants by Staphylococcus aureus. J. Bacteriol. 44:127136.
118. Youmans, G. P.,, E. H. Williston,, and M. Simon. 1945. Production of small colony variants of Staphylococcus aureus by the action of penicillin. Proc. Soc. Exp. Biol. Med. 58:5657.
119. Yu, F. P.,, and G. A. McFeters. 1994. Physiological responses of bacteria in biofilms to disinfection. Appl. Environ. Microbiol. 60:24622466.


Generic image for table
Table 1

Regulation of staphylococcal toxin production

Citation: Proctor R, Bates D, McNamara P. 2001. Electron Transport-Deficient Staphylococcus aureus Small-Colony Variants as Emerging Pathogens, p 95-110. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 5. ASM Press, Washington, DC. doi: 10.1128/9781555816988.ch6
Generic image for table
Table 2

SCV phenotype and exoprotein regulation in

Citation: Proctor R, Bates D, McNamara P. 2001. Electron Transport-Deficient Staphylococcus aureus Small-Colony Variants as Emerging Pathogens, p 95-110. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 5. ASM Press, Washington, DC. doi: 10.1128/9781555816988.ch6

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