Yonsei Med J.  2007 Apr;48(2):176-183. 10.3349/ymj.2007.48.2.176.

Accessory Gene Regulator Group Polymorphisms in Methicillin-Resistant Staphylococcus aureus: An Association with Clinical Significance

Affiliations
  • 1Department of Internal Medicine, Eulji University College of Medicine, Daejeon, Korea.
  • 2Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. imfell@yumc.yonsei.ac.kr
  • 3AIDS Research Institute, Yonsei University College of Medicine, Seoul, Korea.
  • 4Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea.

Abstract

PURPOSE
Virulent gene expression in Staphylococcus aureus is controlled by regulators such as the accessory gene regulator (agr). Strains can be divided into four major agr groups (agr I-IV) on the basis of agrD and agrC polymorphisms. The purpose of this study was to define the proportion of agr I, II, and III polymorphisms and to compare the clinical characteristics between group I and non-group I polymorphisms of methicillin-resistant Staphylococcus aureus (MRSA) strains in a Korean tertiary care teaching hospital. MATERIALS AND METHODS: A total of 158 clinical isolates were evaluated by RFLPs (restriction fragment length polymorphisms). RESULTS: The mean age of the patients was 50.2 +/- 21.9 years old. There were 74 (49.3%), 66 (44.0%), 10 (6.7%), 7 (4.4%), and 1 (0.6%) strains in agr group I, II, III, I + II, and I + III polymorphisms, respectively. Only ear infections were a statistically significant clinical parameter according to univariate (p=0.001) and multivariate analysis (OR, 4.721 (1.273-17.508), p=0.020). CONCLUSION: This study suggests that agr group I is the most prevalent in Korea, and ear infections are correlated with the group I polymorphism, which is a different clinical trend from western countries. It can also be inferred that community-acquired MRSA correlates with agr group I.

Keyword

Staphylococcus aureus; agr polymorphism; otitis

Figure

  • Fig. 1 Representative RFLP analysis with DraI of an amplified portion of the agr locus in MRSA strains on 1.2% agarose gel. M: DNA ladder size marker, A1-5: MRSA strains of agr polymorphism group I, B6-10: group II, C11-12: group II, 13, group I+III, 14, group I+II, D15-18: group III.

  • Fig. 2 The numbers of each agr group from 2002 to 2004.


Reference

1. Arbuthnott JP, Coleman DC, de Azavedo JS. Staphylococcal toxins in human disease. Soc Appl Bacteriol Symp Ser. 1990. 19:101S–107S.
2. Lina G, Gillet Y, Vandenesch F, Jones ME, Floret D, Etienne J. Toxin involvement in staphylococcal scalded skin syndrome. Clin Infect Dis. 1997. 25:1369–1373.
3. Novick RP. Fischetti VA, Novick RP, Ferretti JJ, Portnoy DA, Rood JI, editors. Pathogenicity factors and their regulation. Gram-positive pathogens. 2000. Washington, DC: ASM Press;392–407.
4. Projan S, Novick R. Archer G, Crossley K, editors. The molecular basis of pathogenicity. Staphylococci in human diseases. 1997. New York, N.Y.: Churchill Livingstone;55–81.
5. Bohach GA, Fast DJ, Nelson RD, Schlievert PM. Staphylococcal and streptococcal pyrogenic toxins involved in toxic shock syndrome and related illnesses. Crit Rev Microbiol. 1990. 17:251–272.
6. Lan R, Reeves PR. Intraspecies variation in bacterial genomes: the need for a species genome concept. Trends Microbiol. 2000. 8:396–401.
7. Ji G, Beavis R, Novick RP. Bacterial interference caused by autoinducing peptide variants. Science. 1997. 276:2027–2030.
8. Morfeldt E, Tegmark K, Arvidson S. Transcriptional control of the agr-dependent virulence gene regulator, RNA III, in Staphylococcus aureus. Mol Microbiol. 1996. 21:1227–1237.
9. Novick RP, Ross HF, Projan SJ, Kornblum J, Kreiswirth B, Moghazeh S. Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule. EMBO J. 1993. 12:3967–3975.
10. Peng HL, Novick RP, Kreiswirth B, Kornblum J, Schlievert P. Cloning, characterization, and sequencing of an accessory gene regulator (agr) in Staphylococcus aureus. J Bacteriol. 1988. 170:4365–4372.
11. Recsei P, Kreiswirth B, O'Reilly M, Schlievert P, Gruss A, Novick RP. Regulation of exoprotein gene expression in Staphylococcus aureus by agar. Mol Gen Genet. 1986. 202:58–61.
12. Abdelnour A, Arvidson S, Bremell T, Ryden C, Tarkowski A. The accessory gene regulator (agr) controls Staphylococcus aureus virulence in a murine arthritis model. Infect Immun. 1993. 61:3879–3885.
13. Cheung AL, Eberhardt KJ, Chung E, Yeaman MR, Sullam PM, Ramos M, et al. Diminished virulence of a sar-/agr- mutant of Staphylococcus aureus in the rabbit model of endocarditis. J Clin Invest. 1994. 94:1815–1822.
14. Gillaspy AF, Hickmon SG, Skinner RA, Thomas JR, Nelson CL, Smeltzer MS. Role of the accessory gene regulator (agr) in pathogenesis of staphylococcal osteomyelitis. Infect Immun. 1995. 63:3373–3380.
15. Herold BC, Immergluck LC, Maranan MC, Lauderdale DS, Gaskin RE, Boyle-Vavra S, et al. Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk. JAMA. 1998. 279:593–598.
16. Kim JM, Park ES, Jeong JS, Kim KM, Kim JM, Oh HS, et al. 1996 national nosocomial infection surveillance in Korea. Korean J Nosocomial Infect Control. 1997. 2:157–176.
17. Kloos WE, Bannerman TL. Murray PR, Baron EJ, Pfaller MA, Tenover FC, Yolken RH, editors. Staphylococcus and Micrococcus. Manual of clinical microbiology. 1995. 6th ed. Washington, DC: ASM Press;282–298.
18. National Committee for Clinical Laboratory Standards (NCCLS). Performance standards for antimicrobial susceptibility testing: twelfth informational supplement [M100-S12]. 2002. Wayne, PA: NCCLS.
19. Papakyriacou H, Vaz D, Simor A, Louie M, McGavin MJ. Molecular analysis of the accessory gene regulator (agr) locus and balance of virulence factor expression in epidemic methicillin-resistant Staphylococcus aureus. J Infect Dis. 2000. 181:990–1000.
20. Falkow S. What is a pathogen? ASM News. 1997. 63:359–365.
21. Jeljaszewicz J. Infections caused by staphylococci. Infection. 1983. 11:S109–S111.
22. Booth MC, Cheung AL, Hatter KL, Jett BD, Callegan MC, Gilmore MS. Staphylococcal accessory regulator (sar) in conjunction with agr contributes to Staphylococcus aureus virulence in endophthalmitis. Infect Immun. 1997. 65:1550–1556.
23. Jarraud S, Lyon GJ, Figueiredo AM, Gerard L, Vandenesch F, Etienne J, et al. Exfoliatin-producing strains define a fourth agr specificity group in Staphylococcus aureus. J Bacteriol. 2000. 182:6517–6522.
24. van Leeuwen W, van Nieuwenhuizen W, Gijzen C, Verbrugh H, van Belkum A. Population studies of methicillin-resistant and -sensitive Staphylococcus aureus strains reveal a lack of variability in the agrD gene, encoding a staphylococcal autoinducer peptide. J Bacteriol. 2000. 182:5721–5729.
25. Jarraud S, Mougel C, Thioulouse J, Lina G, Meugnier H, Forey F, et al. Relationships between Staphylococcus aureus genetic background, virulence factors, agr groups (alleles), and human disease. Infect Immun. 2002. 70:631–641.
26. Sakoulas G, Eliopoulos GM, Moellering RC Jr, Wennersten C, Venkataraman L, Novick RP, et al. Accessory gene regulator (agr) locus in geographically diverse Staphylococcus aureus isolates with reduced susceptibility to vancomycin. Antimicrob Agents Chemother. 2002. 46:1492–1502.
27. Moise-Broder PA, Sakoulas G, Eliopoulos GM, Schentag JJ, Forrest A, Moellering RC Jr. Accessory gene regulator group II polymorphism in methicillin-resistant Staphylococcus aureus is predictive of failure of vancomycin therapy. Clin Infect Dis. 2004. 38:1700–1705.
28. Pearman JW. Community-acquired MRSA: the Australian experience [abstract 359]. Program and abstracts of the 10th International Symposium on Staphylococci and Staphylococcal Diseases (Tsukuba, Japan). 2002. Japan: Japan Symposium on Staphylococci and Staphylococcal Diseases;18.
29. Naimi TS. Community-acquired MRSA: the American experience [abstract 352]. Program and abstracts of the 10th International Symposium on Staphylococci and Staphylococcal Diseases (Tsukuba, Japan). 2002. Japan: Japan Symposium on Staphylococci and Staphylococcal Diseases;19.
30. Dufour P, Gillet Y, Bes M, Lina G, Vandenesch F, Floret D, et al. Community-acquired methicillin-resistant Staphylococcus aureus infections in France: emergence of a single clone that produces Panton-Valentine leukocidin. Clin Infect Dis. 2002. 35:819–824.
31. Goerke C, Kymmel M, Dietz K, wolz C. Evaluation of intraspecies interference due to agr polymorphism in Staphylococcus aureus during infection and colonization. J Infect Dis. 2003. 188:250–256.
32. Manago K, Nishi J, Wakimoto N, Miyanohara H, Sarantuya J, Tokuda K, et al. Biofilm formation by and accessory gene regulator typing of methicillin-resistant Staphylococcus aureus strains recovered from patients with nosocomial infections. Infect Control Hosp Epidemiol. 2006. 27:188–190.
33. Yamashita S, Yamaguchi H, Sakaguchi M, Satsumae T, Yamamoto S, Shinya F. Longer-term diabetic patients have a more frequent incidence of nosocomial infections after elective gastrectomy. Anesth Analg. 2000. 91:1176–1181.
34. Ganguly P, Yunus M, Khan A, Malik A. A study of nosocomial infection in relation to different host factors in an Indian teaching hospital. J R Soc Health. 1995. 115:244–246.
35. Gomes AR, Vinga S, Zavolan M, de Lencastre H. Analysis of the genetic variability of virulence-related loci in epidemic clones of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2005. 49:366–379.
36. Novick RP. Dunny GM, Winans SC, editors. Regulation of pathogenicity in Staphylococcus aureus by a peptide-based density-sensing system. Cell-cell signaling in bacteria. 1999. Washington, DC: ASM Press;129–146.
37. Mayville P, Ji G, Beavis R, Yang H, Goger M, Novick RP, et al. Structure-activity analysis of synthetic autoinducing thiolactone peptides from Staphylococcus aureus responsible for virulence. Proc Natl Acad Sci U S A. 1999. 96:1218–1223.
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