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REVIEW PAPERS

Small colony variants of staphylococci: Pathogenesis and evolutionary significance in causing and sustaining problematic human infections

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Pages 56-75 | Published online: 13 Jul 2009

References:

  • Kolle W., Hetsch H. Die experimentelle Bacteriologie und die Infektionsskrankheiten mit bosonderer Berucksochtigung der Immunitatslehre. 3rd ed. Urban and Schioarzeberg, Berlin 1913
  • Swingle E. Studies on Small Colony Variants of Staphylococcus aureus. J. Bacteriol. 1934; 29: 467–489
  • Sherris J. C. Two small colony variants of S. aureus isolated in pure culture from closed infected lesions and their carbondioxide requirements. J. Clin. Pathol. 1952; 5: 354–355
  • Wise R. I. Small colonies (G variants) of staphylococci: isolation from cultures and infections. Ann. N. Y. Acad. Sci. 1956; 65: 69–74
  • McNamara P. J., Proctor R. A. Staphylococcus aureus small colony variants, electron transport and persistent infections. Int J Antimicrob Agents 2000; 14((2))117–22
  • Schnitzer R. J., Camagni L. J., Buck M. Resistance of small colony variants (G‐forms) of a staphylococcus toward the bacteriostatic activity of penicillin. Proc. Soc. Exp. Biol. Med 1943; 53: 75
  • Schmitz F. J., von Eiff C., Gondolf M., Fluit A. C., Verhoef J., Peters G., Hadding U., Heinz H. P., Jones M. Staphylococcus aureus small colony variants: Rate of selection and MIC values compared to wildtype strains using ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and moxifloxacin. Clin. Microbiol. Infect. 1999; 5: 376–378
  • Adler H., Widmer A., Frei R. Emergence of a Teicoplanin‐resistant small colony variant of Staphylococcus epidermidis during vancomycin therapy. Eur. J. Clin. Microbiol Infect. Dis 2003; 22: 746–748
  • Seifert H., Oltmanns D., Becker K., Wisplinghoff H., von Eiff C. Staphylococcus lugdunensis pacemaker‐related infection. Emerg Infect Dis 2005; 11((8))1283–6
  • Haussler S., Tummler B., Weissbrodt H., Rohde M., Steinmetz I. Small‐colony variants of Pseudomonas aeruginosa in cystic fibrosis. Clin Infect Dis 1999; 29((3))621–5
  • Colwell C. A. Small Colony Variants of Escherichia coli. J. Bacteriol 1946; 52: 417–422
  • von Eiff C., Becker K. Small colony variants: Another mechanism by which Staphylococcus aureus can evade the immune response and antimicrobial therapy. MRSA: Current Perspectives, A. C Fluit, F. J Schmitz. Caister Academic Press, Wymondham, UK 2003; 253–273
  • Sadowska B., Bonar A., von Eiff C., Proctor R. A., Chmiela M., Rudnicka W., Rozalska B. Characteristics of Staphylococcus aureus, isolated from airways of cystic fibrosis patients, and their small colony variants. FEMS Immunol Med Microbiol 2002; 32((3))191–7
  • Samuelsen Ø., Haukland H. H., Kahl B. C., von Eiff C., Proctor R. A., Ulvatne H., Sandvik K., Vorland L. H. Staphylococcus aureus small colony variants are resistant to the antimicrobial peptide lactoferricin B. J Antimicrob Chemother 2005; 56((6))1126–1129
  • Spanu T., Romano L., D'Inzeo T., Masucci L., Albanese A., Papacci F., Marchese E., Sanguinetti M., Fadda G. Recurrent ventriculoperitoneal shunt infection caused by small‐colony variants of Staphylococcus aureus. Clin Infect Dis 2005; 41((5))e48–52
  • Baddour L. M., Simpson W. A., Weems J. J., Hill M., Christensen G. D. Phenotypic selection of small colony variant forms of Staphylococcus epidermidis in the rat model of endocarditis. J. Infect. Dis 1988; 157: 757–763
  • Bates D. M., von Eiff C., McNamara P. J., Peters G., Yeaman M. R., Bayer A. S., Proctor R. A. Staphylococcus aureus menD and hemB mutants are as infective as the parent strains, but the menadione biosynthetic mutant persists within the kidney. J Infect Dis 2003; 187((10))1654–61
  • von Eiff C., Heilmann C., Proctor R. A., Woltz C., Peters G., Gotz F. A site‐directed Staphylococcus aureus hemB mutant is a small‐colony variant which persists intracellularly. J Bacteriol 1997; 179((15))4706–4712
  • Massey R. C., Buckling A., Peacock S. J. Phenotypic switching of antibiotic resistance that circumvents permanent costs in Staphylococcus aureus. Curr. Biol. 2001; 11: 1810–1814
  • Schaaff F., Bierbaum G., Baumert N., Bartmann P., Sahl H. G. Mutations are involved in emergence of aminoglycoside‐induced small colony variants of Staphylococcus aureus. Int J Med Microbiol 2003; 293((6))427–35
  • von Eiff C., Peters G., Becker K. The small colony variant (SCV) concept‐ the role of staphylococcal SCVs in persistent infections. Injury, Int. J. Care Injured 2006; 37: S26–S33
  • Sifri C. D., Baresch‐Bernal A., Calderwood S. B., von Eiff C. Virulence of Staphylococcus aureus small colony variants in the Caenorhabditis elegans infection model. Infect Immun 2006; 74((2))1091–1096
  • Looney W. J. Small‐colony variants of Staphylococcus aureus. Br J Biomed Sci 2000; 57((4))317–22
  • Kahl B. C., Belling G., Reichelt R., Herrmann M., Proctor R. A., Peters G. Thymidine‐dependant small colony variants of Staphylococcus aureus exhibit gross morphological and ultra‐structural changes consistent with impaired cell separation. J. Clin. Microbiol 2003; 41: 410–413
  • Baumert N., von Eiff C., Schaaff F., Peters G., Proctor R. A., Sahl H. G. Physiology and antibiotic susceptibility of Staphylococcus aureus small colony variants. Microb. Drug Resist. 2002; 8: 253–260
  • Brouillette E., Martinez A., Boyll B. J., Allen N. E., Malouin F. Persistence of a Staphylococcus aureus small‐colony variant under antibiotic pressure in vivo. FEMS Immunol. Med. Microbiol 2004, (41): 35–41
  • Drenkard E., Ausubel F. M. Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation. Nature 2002; 416: 740–743
  • Roggenkamp A., Hoffmann H., Hornef M. W. Growth control of small‐colony variants by genetic regulation of the hemin uptake system. Infect Immun 2004; 72((4))2254–62
  • Prescott L. M., Harley J. P., Klein D. A. Microbiology. 6th ed. McGraw‐Hill Companies, NY 2004
  • Moisan H., Brouillette E., Jacob C. L., Langlois‐Begin P., Michaud S., Malouin F. Transcription of virulence factors in Staphylococcus aureus small‐colony variants isolated from cystic fibrosis patients is influenced by SigB. J Bacteriol 2006; 188((1))64–76
  • McGregor N. R., Butt H. L., Klineberg I. J. Myogenous cranio‐mandibular disorders: A preliminary report of a systemic aetiology. J. Orofac. Pain 1993; 7: 108
  • McGregor N. R., Butt H. L., Zerbes M., Klineberg I. J., Dunstan R. H., Roberts T. K. Assessment of pain (distribution and onset), symptoms and the association with infectious events in subjects with chronic orofacial pain. J. Orofac. Pain 1996; 10: 339–350
  • Butt H. L., Dunstan R. H., McGregor N. R., Roberts T. K., Zerbes M., Klineberg I. J. An association of membrane‐damaging toxins from coagulase negative staphylococci and chronic orofacial muscle pain. J. Med. Microbiol. 1998; 47: 577–584
  • Proctor R. A., von Eiff C., Kahl B. C., Becker K., McNamara P., Herrmann M., Peters G. Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections. Nat Rev Microbiol 2006; 4((4))295–305
  • Proctor R. A., Balwit J. M., Vesga O. Variant subpopulations of Staphylococcus aureus as cause of persistent and recurrent infections. Infect. Agents Dis 1994; 3: 302–312
  • Roggenkamp A., Sing A., Hornef M., Brunner U., Autenrieth U. B., Heesemann J. Chronic prosthetic hip infection caused by small colony variants of Escherichia coli. J. Clin. Microbiol 1998; 36: 2530–2534
  • Proctor R. A., Kahl B., von Eiff C., Vaudaux P. E., Lew D. P., Peters G. Staphylococcal small colony variants have novel mechanisms for antibiotic resistance. Clin Infect Dis 1998; 27 Suppl 1: S68–74
  • Balwit J. M., van Langeveld P., Vann J. M., Proctor R. A. Gentamicin‐ resistant menadione and haemin auxotrophic Staphylococcus aureus persist within cultured endothelial cells. J. Infect. Dis. 1994; 170: 1033–1037
  • Proctor R. A., van Langevelde P., Kristjansson M., Maslow J. N., Arbeit R. D. Persistent and relapsing infections associated with small‐colony variants of Staphylococcus aureus. Clin. Infect. Dis 1995; 20: 95–102
  • Wise R. I., Spink W. W. The influence of antibiotics on the origin of small colony (G Variants) of Micrococcus pyogenes var. aureus. J. Clin Invest 1954; 12: 1611–1622
  • Proctor R. A., Peters G. Small colony variants in staphylococcal infections: diagnostic and therapeutic implications. Clin Infect Dis 1998; 27((3))419–22
  • Parsek M., Singh P. Bacterial biofilms: An emerging link to disease pathogenesis. Annu. Rev. Microbiol 2003; 57: 677–701
  • Schwank S., Rajacic Z., Zimmerli W., Blaser J. Impact of bacterial biofilm formation on in vitro and in vivo activities of antibiotics. Antimicrobiol. Agent. Chemo 1998; 42: 895–898
  • Neut D., van der Mei H. C., Bulstra S. K., Busscher H. J. The role of small‐colony variants in failure to diagnose and treat biofilm infections in orthopedics. Acta Orthop 2007; 78((3))299–308
  • Fax C. A., Stoodley P., Stoodley L. H., Costerton J. W. Bacterial Biofilms: A diagnostic and therapeutic challenge. Expert Rev. Anti‐Infect Ther 2003; 4: 667–683
  • Chuard C., Vaudaux P. E., Waldvogel F. A., Lew D. P. Susceptibility of Staphylococcus aureus growing on fibronectin‐coated surfaces to bactericidal antibiotics. Antimicrob. Agents Chemother 1993; 4: 625–632
  • von Eiff C., McNamara P., Becker K., Bates D., Lei X. H., Ziman M., Bochner B. R., Peters G., Proctor R. A. Phenotype microarray profiling of Staphylococcus aureus menD and hemB mutants with the small‐colony‐variant phenotype. J Bacteriol 2006; 188((2))687–693
  • Bayston R. Biofilms and prosthetic devices. Community structure and co‐operation in biofilms, D. G Allison, P Gilbert, H. M Lappin‐Scott, M Wilson, 2000; 295–308
  • Fleurette J., Bes M., Brun Y., Freney J., Forey F., Coulet M., Reverdy M. E., Etienne J. Clinical isolates of Staphylococcus lugdunensis and S. schleiferi: Bacteriological characteristics and susceptibility to antimicrobial agents. Res. Microbiol. 1989; 140: 107–118
  • Herchline T. E., Ayers L. W. Occurrence of Staphylococcus lugdunensis in consecutive clinical cultures and relationship of isolation to infection. J. Clin. Microbiol 1991; 29: 419–421
  • Koh T. W., Brecker S. J. D., Leyton C. A. Successful treatment of Staphylococcus lugdunensis endocarditis complicated by multiple emboli: A case report and review of the literature. Int. J. Cardiol. 1996; 55: 193–197
  • Leung M. J., Nuttall N., Pryce T. M., Coombs G. W., Pearman J. W. Colony variation in Staphylococcus lugdunensis. J. Clin. Microbiol 1998; 36: 3096–3098
  • Abele‐Horn M., Schupfner B., Emmerling P., Waldner H., Goring H. Persistent wound infection after herniotomy associated with small‐colony variants of Staphylococcus aureus. Infection 2000; 28: 53–54
  • Proctor R. A., von Humboldt A. Bacterial energetics and antimicrobial resistance. Drug Resist Updat 1998; 1((4))227–35
  • Kahl B. C., Belling G., Becker P., Chatterjee I., Wardecki K., Hilgert K., Cheung A. L., Peters G., Herrmann M. Thymidine‐dependant Staphylococcus aureus small colony variants are associated with extensive alterations in regulator and virulence gene expression profiles. Infect. Immun 2005; 73: 4119–4126
  • von Eiff C., Bettin D., Proctor R. A., Rolauffs B., Lindner N., Winkelmann W., Peters G. Recovery of small colony variants of Staphylococcus aureus following gentamicin bead placement for osteomyelitis. Clin Infect Dis 1997; 25((5))1250–1251
  • Hogan D., Kolter R. Why are bacteria refractory to antimicrobials?. Curr. Opin. Microbiol 2002; 5: 472–477
  • Fries B. C., Taborda C. P., Serfass E., Casadevall A. Phenotypic switching of Cryptococcus neoformans occurs in vivo and influences the outcome of infection. J Clin Invest 2001; 108((11))1639–48
  • Huebner J., Goldmann D. A. Coagulase‐negative Staphylococci: Role as pathogens. Annu. Rev. Med 1999; 50: 223–236
  • von Eiff C., Proctor R. A., Peters G. Coagulase‐negative staphylococci: Pathogens have a major role in nosocomial infections. Postgrad. Med 2001; 110: 63–76
  • von Eiff C., Vaudaux P., Kahl B. C., Lew D., Emler S., Schmidt A., Peters G., Proctor R. A. Bloodstream infections caused by small‐colony variants of coagulase‐negative staphylococci following pacemaker implantation. Clin Infect Dis 1999; 29((4))932–4
  • Woo P. C. Y., Wong S. S. Y., Lum P. N. L., Hui W. T., Yuen K. Y. Cell‐wall‐deficient bacteria and culture‐negative febrile episodes in bone‐marrow transplant recipients. Lancet 2001; 357: 675–679
  • Mattman H. L. History. Cell Wall Deficient Forms: Stealth Pathogens. 3rd ed. CRC Press LLC, FL 2000
  • Bulger R. J., Bulger R. E. Ultrastructure of small colony variants of a methicillin‐resistant Staphylococcus aureus. J. Bacteriol 1967; 94: 1244–1246
  • Chuard C., Vaudaux P. E., Proctor R. A., Lew D. P. 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. 1997; 39: 603–608
  • Morris A., Kellner J. D., Low D. E. The superbugs: evolution, dissemination and fitness. Curr. Opin. Microbiol. 1998; 1: 524–529
  • Crisóstomo M. I., Westh H., Tomasz A., Chung M., Oliveira D. C., de Lencastre H. The evolution of methicillin resistance in Staphylococcus aureus: Similarity of genetic backgrounds in historically early methicillin‐suscpetible and ‐resistant isolates and contemporary epidemic clones. Proc. Natl Acad. Sci. 2001; 98: 9865–9870
  • von Eiff C., Becker K., Metze D., Lubritz G., Hockmann J., Schwarz T., Peters G. 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 2001; 32((11))1643–7
  • Foster T. J. Immune evasion by staphylococci. Nature Rev 2005; 3: 948–958
  • Schroder A., Kland R., Peschel A., von Eiff C., Aepfelbacher M. Live cell imaging of phagosome maturation in Staphylococcus aureus infected human endothelial cells: small colony variants are able to survive in lysosomes. Med Microbiol Immunol (Berl) 2006; 195((4))185–94
  • Brooks G. F., Butel J. S., Ornston L. N. Jawetz, Melnick and Adelberg's Medical Microbiology. 20th ed. Appleton & Lange, NorwalkUSA</countr> 1995
  • Murray P. R., Drew W. L., Kobayashi G. S., Thompson J. H. Medical Microbiology. 3rd ed. 1990, Wolfe Medical Publications Ltd
  • Mayer G. Rickettsia, Orientia, Ehrlichia, Anaplasma, Coxiella and Bartonella. R. C Hunt, In: Microbiology and Immunology On‐line
  • Belland R. J., Scidmore M. A., Crane D. D., Hogan D. M., Whitmire W., McClarty G., Caldwell H. D. Chlamydia trachomatis cytotoxicity associated with complete and partial cytotoxin genes. Proc. Natl. Acad. Sci. 2001; 98: 13984–13989
  • Peacock S. J., Foster T. J., Cameron B. J., Berendt A. R. Bacterial fibronectin‐binding proteins and endothelial cell surface fibronectin mediate adherence of Staphylococcus aureus to resting human endothelial cells. Microbiology 1999; 145((Pt 12))3477–86
  • Vaudaux P., Francois P., Bisognano C., Kelley W. L., Lew D. P., Schrenzel J., Proctor R. A., McNamara P. J., Peters G., Von Eiff C. Increased expression of clumping factor and fibronectin‐binding proteins by hemB mutants of Staphylococcus aureus expressing small colony variant phenotypes. Infect Immun 2002; 70((10))5428–37
  • Vesga O., Groeschel M. C., Otten M. F., Brar D. W., Vann J. M., Proctor R. A. Staphylococcus aureus small colony variants are induced by the endothelial cell intracellular milieu. J. Infect. Dis. 1996; 173: 739–742
  • Abbas A. K., AH L. Basic Immunology: Functions and Disorders of the Immune System. 2nd ed. 2004, Elsevier Inc
  • Kipp F., Kahl B. C., Becker K., Baron E. J., Proctor R. A., Peters G., von Eiff C. Evaluation of two chromogenic agar media for recovery and identification of Staphylococcus aureus small‐colony variants. J Clin Microbiol 2005; 43((4))1956–9
  • Salgado D. R., Boza F. A., Pinto M., Sampaio J. Outbreak with small colony variants of methicillin‐resistant Staphylococcus aureus in an ICU. Interscience Conference on Antimicrobial Agents and Chemotherapy. National Library of Medicine, Chicago, IL 2001, p. Conference paper
  • Seifert H., Wisplinghoff H., Schnabel P., von Eiff C. Small colony variants of Staphylococcus aureus and pacemaker‐related infection. Emerg Infect Dis 2003; 9((10))1316–8
  • Patel R., Piper K. E., Rouse M. S., Uhl J. R., Cockerill F., Steckelberg. Frequency of isolation of Staphylococcus lugdunensis among staphylococcal isolates causing endocarditis: a 20 yr experience. J. Clin. Microbiol 2000; 38: 4262–4263
  • von Eiff C., Peters G., Heilmann C. Pathogenesis of infection due to coagulase negative staphylococci. Lancet Infect Dis 2002; 2: 677–685
  • Holmes G. P., Kaplan J. E., Gantz N. M., Komaroff A. L., Schonberger L. B., Straus S. E., Jones J. F., Dubois R. E., Cunningham‐Rundles C., Pahwa S. Chronic fatigue syndrome: A working case definition. Ann. Intern. Med. 1988; 108: 387–389
  • Fukuda K., Straus S. E., Hickie I., Sharpe M. C., Dobbins J. G., Komaroff A., International Chronic Fatigue Syndrome Study Group. The chronic fatigue syndrome: A comprehensive approach to its definition and study. Ann. Intern. Med. 1994; 121: 953–959
  • McGregor N. R., Zerbes M., Butt H. L., Niblett S. H., Dunstan R. H., Roberts T. K., Klineberg I. J. Coagulase negative staphylococcal membrane‐damaging toxins, pain intensity and metabolic changes in temporomandibular disorder patients with chronic muscle pain. J. Orofac. Pain 2003; 17: 125–132
  • Tarello W. Chronic Fatigue Syndrome associated with Staphylococcus spp. Bacteraemia Responsive to Potassium Arsenite 0.5% in a Veterinary Surgeon and His Co‐working Wife Handling with CFS Animal Cases. Comp. Immunol. Microbiol. Infect. Dis. 2001; 24: 233–246
  • Andersson M., Bagby J. R., Dyrehag L. E., Gottfries C. G. Effects of Staphylococcus toxoid vaccine on pain and fatigue in patients with fibromyalgia/chronic fatigue syndrome. Eur. J. Pain 1998; 2: 133–142
  • Zachrisson O., Regland B., Jahreskog M., Jonsson M, M. K., Gottfries C. G. Treatment with staphylococcus toxoid in fibromyalgia/chronic fatigue syndrome – A randomized controlled trial. Eur. J. Pain 2002; 6: 455–566
  • Davies J., Wright G. D. Bacterial resistance to aminoglycoside antibiotics. Trends Microbiol 1997; 5: 234–240
  • Mandell G. L., Bennett J. E., Dolin R. Mandell, Douglas and Bennette's Principles and Practise of Infectious Diseases. 5th ed. Churchill Linvingstone, UK 2000
  • Heinsbroek S., Brown G. D., Gordon S. Dectin‐1 escape of fungal dimorphism. Trends Immunol 2005; 26: 352–354
  • Wainwright M. Highly pleomorphic staphylococci as a cause of cancer. Med. Hypotheses 2000; 1: 91–94
  • Rice L. Evolution and clinical importance of extended‐spectrum β‐lactamases. Chest 2001; 119: 391–396

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