Key genetic elements and regulation systems in methicillin-resistant Staphylococcus aureus

Future Microbiology

Volumn 7, Issue 11, 2012, Pages 1315-1329

  Hao, Haihong ^a   Dai, Menghong ^a   Wang, Yulian ^a   Huang, Lingli ^a   Yuan, Zonghui ^a  

^a HUAZHONG AGRICULTURAL UNIVERSITY   (China)

Author keywords

genetic elements; MRSA; multiresistance; pathogenesis; regulation systems

Indexed keywords

ANTIINFECTIVE AGENT; ARGININE; BACTERIAL ENZYME; BETA LACTAM ANTIBIOTIC; CFT ENZYME; PANTON VALENTINE LEUKOCIDIN; UNCLASSIFIED DRUG; VIRULENCE FACTOR;

BACTERIAL GENE; CHROMOSOME; GEOGRAPHIC DISTRIBUTION; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; MULTIDRUG RESISTANCE; NONHUMAN; NUCLEOTIDE SEQUENCE; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; SCCMEC BACTERIAL GENE;

BETA-LACTAMASES; GENE EXPRESSION REGULATION, FUNGAL; HUMANS; METHICILLIN RESISTANCE; METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS; STAPHYLOCOCCAL INFECTIONS; VIRULENCE FACTORS;

EID: 84867728555     PISSN: 17460913     EISSN: 17460921     Source Type: Journal    
DOI: 10.2217/fmb.12.107     Document Type: Review

References (132)

1. Morell EA, Balkin DM. Methicillin-resistant Staphylococcus aureus: A pervasive pathogen highlights the need for new antimicrobial development. Yale J. Biol. Med. 83, 223-233 (2010).
2. Konrad P, Adriana ER, Grzegorz W. Staphylococcus aureus as an infectious agent: Overview of biochemistry and molecular genetics of its pathogenicity. Acta Biochim. Pol. 56, 16 (2009).
3. DeLeo FR, Chambers HF. Reemergence of antibiotic-resistant Staphylococcus aureus in the genomics era. J. Clin. Invest. 119, 2464-2474 (2009).
4. Barber M. Methicillin-resistant staphylococci. J. Clin. Pathol. 14, 385-393 (1961).
5. Stapleton PD, Taylor PW. Methicillin resistance in Staphylococcus aureus: Mechanisms and modulation. Sci. Prog. 85, 57-72 (2002).
6. Wenzel RP. The emergence of methicillinresistant Staphylococcus aureus. Ann. Intern. Med. 97, 440-442 (1982).
7. Haley RW, Hightower AW, Khabbaz RF et al. The emergence of methicillin-resistant Staphylococcus aureus infections in United States hospitals. Possible role of the house staff-patient transfer circuit. Ann. Intern. Med. 97, 297-308 (1982).
8. Jones ME, Karlowsky JA, Draghi DC, Thornsberry C, Sahm DF, Nathwani D. Epidemiology and antibiotic susceptibility of bacteria causing skin and soft tissue infections in the USA and Europe: A guide to appropriate antimicrobial therapy. Int. J. Antimicrob. Agents 22, 406-419 (2003).
9. Jones ME, Draghi DC, Thornsberry C, Karlowsky JA, Sahm DF, Wenzel RP. Emerging resistance among bacterial pathogens in the intensive care unit -a European and North American Surveillance study (2000-2002). Ann. Clin. Microbiol. Antimicrob. 3, 14 (2004).
10. Pan ES, Diep BA, Charlebois ED et al. Population dynamics of nasal strains of methicillin-resistant Staphylococcus aureus - And their relation to community-associated disease activity. J. Infect. Dis. 192, 811-818 (2005).
11. Maree CL, Daum RS, Boyle-Vavra S, Matayoshi K, Miller LG. Communityassociated methicillin-resistant Staphylococcus aureus isolates causing healthcare-associated infections. Emerg. Infect. Dis. 13, 236-242 (2007).
12. Labandeira-Rey M, Couzon F, Boisset S et al. Staphylococcus aureus Panton-Valentine leukocidin causes necrotizing pneumonia. Science 315, 1130-1133 (2007).
13. Catry B, Van Duijkeren E, Pomba MC et al. Reflection paper on MRSA in food-producing and companion animals: Epidemiology and control options for human and animal health. Epidemiol. Infect. 138, 626-644 (2010).
14. Holmes MA, Zadoks RN. Methicillin resistant Staphylococcus aureus in human and bovine mastitis. J. Mammary Gland Biol. Neoplasia 16, 373-382 (2011).
15. Vanderhaeghen W, Hermans K, Haesebrouck F, Butaye P. Methicillin- resistant Staphylococcus aureus (MRSA) in food production animals. Epidemiol. Infect. 138, 606-625 (2010).
16. Broens EM, Graat EA, Van Der Wolf PJ, Van De Giessen AW, De Jong MC. Prevalence and risk factor analysis of livestock associated MRSA-positive pig herds in The Netherlands. Prev. Vet. Med. 102, 41-49 (2011).
17. Wilke MS, Hills TL, Zhang HZ, Chambers HF, Strynadka NC. Crystal structures of the Apo and penicillin-acylated forms of the BlaR1 beta-lactam sensor of Staphylococcus aureus. J. Biol. Chem. 279, 47278-47287 (2004).
18. Smith LK, Mankin AS. Transcriptional and translational control of the mlr operon, which confers resistance to seven classes of protein synthesis inhibitors. Antimicrob. Agents Chemother. 52, 1703-1712 (2008).
19. Argudín MA, Tenhagen BA, Fetsch A et al. Virulence and resistance determinants of German Staphylococcus aureus ST398 isolates from nonhuman sources. Appl. Environ. Microbiol. 77, 3052-3060 (2011).
20. Bubeck Wardenburg J, Bae T, Otto M, Deleo FR, Schneewind O. Poring over pores: Alpha-hemolysin and Panton-Valentine leukocidin in Staphylococcus aureus pneumonia. Nat. Med. 13, 1405-1406 (2007).
21. Lo WT, Wang CC. Panton-Valentine leukocidin in the pathogenesis of communityassociated methicillin-resistant Staphylococcus aureus infection. Pediatr. Neonatol. 52, 59-65 (2011).
22. Queck SY, Khan BA, Wang R et al. Mobile genetic element-encoded cytolysin connects virulence to methicillin resistance in MRSA. Plos Pathog. 5, e1000533 (2009).
23. de Lencastre H, Oliveira D, Tomasz A. Antibiotic resistant Staphylococcus aureus: A paradigm of adaptive power. Curr. Opin. Microbiol. 10, 428-435 (2007).
24. Nygaard TK, Pallister KB, Ruzevich P, Griffith S, Vuong C, Voyich JM. SaeR binds a consensus sequence within virulence gene promoters to advance USA300 pathogenesis. J. Infect. Dis. 201, 241-254 (2010).
25. Pantosti A, Sanchini A, Monaco M. Mechanisms of antibiotic resistance in Staphylococcus aureus. Future Microbiol. 2, 323-334 (2007).
26. Zhang HZ, Hackbarth CJ, Chansky KM, Chambers HF. A proteolytic transmembrane signaling pathway and resistance to beta-lactams in staphylococci. Science 291, 1962-1965 (2001).
27. Lim D, Strynadka NC. Structural basis for the beta lactam resistance of PBP2a from methicillin-resistant Staphylococcus aureus. Nat. Struct. Biol. 9, 870-876 (2002).
28. Safo MK, Ko TP, Musayev FN, Zhao Q, Wang AH, Archer GL. Structure of the MecI repressor from Staphylococcus aureus in complex with the cognate DNA operator of mec. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 62, 320-324 (2006).
29. Kobayashi N, Taniguchi K, Urasawa S. Analysis of diversity of mutations in the mecI gene and mecA promoter/operator region of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Antimicrob. Agents Chemother. 42, 717-720 (1998).
30. Hou Z, Meng JR, Niu C et al. Restoration of antibiotic susceptibility in methicillinresistant Staphylococcus aureus by targeting mecR1 with a phosphorothioate deoxyribozyme. Clin. Exp. Pharmacol. Physiol. 34, 1160-1164 (2007).
31. Rosato AE, Kreiswirth BN, Craig WA, Eisner W, Climo MW, Archer GL. mecA-blaZ corepressors in clinical Staphylococcus aureus isolates. Antimicrob. Agents Chemother. 47, 1460-1463 (2003).
32. Milheiriço C, Portelinha A, Krippahl L, de Lencastre H, Oliveira D. Evidence for a purifying selection acting on the b-lactamase locus in epidemic clones of methicillinresistant Staphylococcus aureus. BMC Microbiol. 15, 76 (2011).
33. Niemeyer DM, Pucci MJ, Thanassi JA, Sharma VK, Archer GL. Role of mecA transcriptional regulation in the phenotypic expression of methicillin resistance in Staphylococcus aureus. J. Bacteriol. 178, 5464-5471 (1996).
34. Weller TM. The distribution of mecA, mecR1 and mecI and sequence analysis of mecI and the mec promoter region in staphylococci expressing resistance to methicillin. J. Antimicrob. Chemother. 43, 15-22 (1999).
35. Oliveira DC, de Lencastre H. Methicillinresistance in Staphylococcus aureus is not affected by the overexpression in trans of the mecA gene repressor: A surprising observation. Plos One 6, e23287 (2011).
36. Ender M, Berger-Bachi B, McCallum N. A novel DNA-binding protein modulating methicillin resistance in Staphylococcus aureus. BMC Microbiol. 9, 15 (2009).
37. Gardete S, Ludovice AM, Sobral RG, Filipe SR, de Lencastre H, Tomasz A. Role of murE in the expression of beta-lactam antibiotic resistance in Staphylococcus aureus. J. Bacteriol. 186, 1705-1713 (2004).
38. Akcam FZ, Tinaz GB, Kaya O, Tigli A, Ture E, Hosoglu S. Evaluation of methicillin resistance by cefoxitin disk diffusion and PBP2a latex agglutination test in mecApositive Staphylococcus aureus, and comparison of mecA with femA, femB, femX positivities. Microbiol. Res. 164, 400-403 (2009).
39. Li X, Xiong Y, Fan X et al. A study of the regulating gene of femA from methicillinresistant Staphylococcus aureus clinical isolates. J. Int. Med. Res. 36, 420-433 (2008).
40. García-Álvarez L, Holden MT, Lindsay H et al. Meticillin-resistant Staphylococcus aureus with a novel mecA homologue in human and bovine populations in the UK and Denmark: A descriptive study. Lancet Infect. Dis. 11, 595-603 (2011).
41. Cuny C, Layer F, Strommenger B, Witte W. Rare occurrence of methicillin-resistant Staphylococcus aureus CC130 with a novel mecA homologue in humans in Germany. Plos One 6, e24360 (2011).
42. Ito T, Katayama Y, Hiramatsu K. Cloning and nucleotide sequence determination of the entire mec DNA of pre-methicillin-resistant Staphylococcus aureus N315. Antimicrob. Agents Chemother. 43, 1449-1458 (1999).
43. Noto MJ, Kreiswirth BN, Monk AB, Archer GL. Gene acquisition at the insertion site for SCCmec, the genomic island conferring methicillin resistance in Staphylococcus aureus. J. Bacteriol. 190, 1276-1283 (2008).
44. Ito T, Katayama Y, Asada K et al. Structural comparison of three types of staphylococcal cassette chromosome mec integrated in the chromosome in methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 45, 1323-1336 (2001).
45. Turlej A, Hryniewicz W, Empel J. Staphylococcal cassette chromosome mec (SCCmec) classification and typing methods: An overview. Pol. J. Microbiol. 60, 95-103 (2011).
46. Ito T, Ma XX, Takeuchi F, Okuma K, Yuzawa H, Hiramatsu K. Novel type V staphylococcal cassette chromosome mec driven by a novel cassette chromosome recombinase, ccrC. Antimicrob. Agents Chemother. 48, 2637-2651 (2004).
47. Baba T, Takeuchi F, Kuroda M et al. Genome and virulence determinants of high virulence community-acquired MRSA. Lancet 359, 1819-1827 (2002).
48. Holden MT, Feil EJ, Lindsay JA et al. Complete genomes of two clinical Staphylococcus aureus strains: Evidence for the rapid evolution of virulence and drug resistance. Proc. Natl Acad. Sci. USA 101, 9786-9791 (2004).
49. Diep BA, Gill SR, Chang RF et al. Complete genome sequence of USA300, an epidemic clone of community-acquired meticillinresistant Staphylococcus aureus. Lancet 367, 731-739 (2006).
50. Hanssen AM, Ericson Sollid JU. SCCmec in staphylococci: Genes on the move. FEMS Immunol. Med. Microbiol. 46, 8-20 (2006).
51. Zhang K, McClure JA, Elsayed S, Conly JM. Novel staphylococcal cassette chromosome mec type, tentatively designated type VIII, harboring class A mec and type 4 ccr gene complexes in a Canadian epidemic strain of methicillin- resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 53, 531-540 (2009).
52. Deurenberg RH, Stobberingh EE. The evolution of Staphylococcus aureus. Infect. Genet. Evol. 8, 747-763 (2008).
53. Okuma K, Iwakawa K, Turnidge JD et al. Dissemination of new methicillin-resistant Staphylococcus aureus clones in the community. J. Clin. Microbiol. 40, 4289-4294 (2002).
54. Malachowa N, DeLeo FR. Mobile genetic elements of Staphylococcus aureus. Cell. Mol. Life Sci. 67, 3057-3071 (2010).
55. Chen L, Mediavilla JR, Smyth DS et al. Identification of a novel transposon (Tn6072) and a truncated staphylococcal cassette chromosome mec element in methicillinresistant Staphylococcus aureus ST239. Antimicrob. Agents Chemother. 54, 3347-3354 (2010).
56. Chongtrakool P, Ito T, Ma XX et al. Staphylococcal cassette chromosome mec (SCCmec) typing of methicillin-resistant Staphylococcus aureus strains isolated in 11 Asian countries: A proposal for a new nomenclature for SCCmec elements. Antimicrob. Agents Chemother. 50, 1001-1012 (2006).
57. Berglund C, Ito T, Ikeda M, Ma XX, Soderquist B, Hiramatsu K. Novel type of staphylococcal cassette chromosome mec in a methicillin-resistant Staphylococcus aureus strain isolated in Sweden. Antimicrob. Agents Chemother. 52, 3512-3516 (2008).
58. Li S, Skov RL, Han X et al. Novel types of staphylococcal cassette chromosome mec elements identified in clonal complex 398 methicillin-resistant Staphylococcus aureus strains. Antimicrob. Agents Chemother. 55, 3046-3050 (2011).
59. Coombs GW, Monecke S, Pearson JC et al. Evolution and diversity of communityassociated methicillin-resistant Staphylococcus aureus in a geographical region. BMC Microbiol. 11, 215 (2011).
60. Pruneau M, Mitchell G, Moisan H, Dumont-Blanchette E, Jacob CL, Malouin F. Transcriptional analysis of antibiotic resistance and virulence genes in multiresistant hospital-acquired MRSA. FEMS Immunol. Med. Microbiol. 63(1), 54-64 (2011).
61. Witte W, Cuny C. Emergence and spread of cfr-mediated multiresistance in staphylococci: An interdisciplinary challenge. Future Microbiol. 6, 925-931 (2011).
62. Locke JB, Rahawi S, Lamarre J, Mankin AS, Shaw KJ. Genetic environment and stability of cfr in methicillin-resistant Staphylococcus aureus CM05. Antimicrob. Agents Chemother. 56, 332-340 (2012).
63. Ruiz de Gopegui E, Juan C, Zamorano L, Perez JL, Oliver A. Transferable multidrug resistance plasmid carrying cfr associated with tet(L), ant(4')-Ia and dfrK genes from a clinical methicillin-resistant Staphylococcus aureus ST125 strain. Antimicrob. Agents Chemother. 56(4), 2139-2142 (2012).
64. Kehrenberg C, Aarestrup FM, Schwarz S. IS21-558 insertion sequences are involved in the mobility of the multiresistance gene cfr. Antimicrob. Agents Chemother. 51, 483-487 (2007).
65. Shore AC, Brennan OM, Ehricht R et al. Identification and characterization of the multidrug resistance gene cfr in a Panton-Valentine leukocidin-positive sequence type 8 methicillin-resistant Staphylococcus aureus IVa (USA300) isolate. Antimicrob. Agents Chemother. 54, 4978-4984 (2010).
66. Kehrenberg C, Cuny C, Strommenger B, Schwarz S, Witte W. Methicillin-resistant and -susceptible Staphylococcus aureus strains of clonal lineages ST398 and ST9 from swine carry the multidrug resistance gene cfr. Antimicrob. Agents Chemother. 53, 779-781 (2009).
67. Kaneko J, Kamio Y. Bacterial two-component and hetero-heptameric pore-forming cytolytic toxins: Structures, pore-forming mechanism, and organization of the genes. Biosci. Biotechnol. Biochem. 68, 981-1003 (2004).
68. Jayasinghe L, Bayley H. The leukocidin pore: Evidence for an octamer with four LukF subunits and four LukS subunits alternating around a central axis. Protein Sci. 14, 2550-2561 (2005).
69. Foster TJ. Immune evasion by staphylococci. Nat. Rev. Microbiol. 3, 948-958 (2005).
70. Kilic A, Li H, Stratton CW, Tang YW. Antimicrobial susceptibility patterns and staphylococcal cassette chromosome mec types of, as well as Panton-Valentine leukocidin occurrence among, methicillinresistant Staphylococcus aureus isolates from children and adults in middle Tennessee. J. Clin. Microbiol. 44, 4436-4440 (2006).
71. Otto M. Basis of virulence in communityassociated methicillin-resistant Staphylococcus aureus. Annu. Rev. Microbiol. 64, 143-162 (2010).
72. Hongo I, Baba T, Oishi K, Morimoto Y, Ito T, Hiramatsu K. Phenol-soluble modulin alpha 3 enhances the human neutrophil lysis mediated by Panton-Valentine leukocidin. J. Infect. Dis. 200, 715-723 (2009).
73. Löffler B, Hussain M, Grundmeier M et al. Staphylococcus aureus Panton-Valentine leukocidin is a very potent cytotoxic factor for human neutrophils. Plos Pathog. 6, e1000715 (2010).
74. Badiou C, Dumitrescu O, George N et al. Rapid detection of Staphylococcus aureus Panton-Valentine leukocidin in clinical specimens by enzyme-linked immunosorbent assay and immunochromatographic tests. J. Clin. Microbiol. 48, 1384-1390 (2010).
75. Graves SF, Kobayashi SD, Braughton KR et al. Relative contribution of Panton-Valentine leukocidin to PMN plasma membrane permeability and lysis caused by USA300 and USA400 culture supernatants. Microbes Infect. 12, 446-456 (2010).
76. Diep BA, Palazzolo-Ballance AM, Tattevin P et al. Contribution of Panton-Valentine leukocidin in community-associated methicillin-resistant Staphylococcus aureus pathogenesis. Plos One 3, e3198 (2008).
77. Montgomery CP, Daum RS. Transcription of inflammatory genes in the lung after infection with community-associated methicillinresistant Staphylococcus aureus: A role for Panton-Valentine leukocidin? Infect. Immun. 77, 2159-2167 (2009).
78. Wang R, Braughton KR, Kretschmer D et al. Identification of novel cytolytic peptides as key virulence determinants for communityassociated MRSA. Nat. Med. 13, 1510-1514 (2007).
79. Kretschmer D, Gleske AK, Rautenberg M et al. Human formyl peptide receptor 2 senses highly pathogenic Staphylococcus aureus. Cell Host Microbe 7, 463-473 (2010).
80. Clarke SR. Phenol-soluble modulins of Staphylococcus aureus lure neutrophils into battle. Cell Host Microbe 7, 423-424 (2010).
81. de Haas CJ, Veldkamp KE, Peschel A et al. Chemotaxis inhibitory protein of Staphylococcus aureus, a bacterial antiinflammatory agent. J. Exp. Med. 199, 687-695 (2004).
82. Prat C, Bestebroer J, de Haas CJ, van Strijp JA, van Kessel KP. A new staphylococcal anti-inflammatory protein that antagonizes the formyl peptide receptor-like 1. J. Immunol. 177, 8017-8026 (2006).
83. Prat C, Haas PJ, Bestebroer J, de Haas CJ, van Strijp JA, van Kessel KP. A homolog of formyl peptide receptor-like 1 (FPRL1) inhibitor from Staphylococcus aureus (FPRL1 inhibitory protein) that inhibits FPRL1 and FPR. J. Immunol. 183, 6569-6578 (2009).
84. Chatterjee SS, Chen L, Joo HS, Cheung GY, Kreiswirth BN, Otto M. Distribution and regulation of the mobile genetic elementencoded phenol-soluble modulin PSM-mec in methicillin-resistant Staphylococcus aureus. Plos One 6, e28781 (2011).
85. Monecke S, Engelmann I, Archambault M et al. Distribution of SCCmec-associated phenol-soluble modulin in staphylococci. Mol. Cell. Probes 26, 99-103 (2012).
86. Otto M. Staphylococcus aureus toxin gene hitchhikes on a transferable antibiotic resistance element. Virulence 1, 49-51 (2010).
87. Kaito C, Saito Y, Nagano G et al. Transcription and translation products of the cytolysin gene psm-mec on the mobile genetic element SCCmec regulate Staphylococcus aureus virulence. Plos Pathog. 7, e1001267 (2011).
88. Katayama Y, Ito T, Hiramatsu K. A new class of genetic element, staphylococcus cassette chromosome mec, encodes methicillin resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 44, 1549-1555 (2000).
89. Nastaly P, Grinholc M, Bielawski KP. Molecular characteristics of communityassociated methicillin-resistant Staphylococcus aureus strains for clinical medicine. Arch. Microbiol. 192, 603-617 (2010).
90. Diep BA, Stone GG, Basuino L et al. The arginine catabolic mobile element and staphylococcal chromosomal cassette mec linkage:Convergence of virulence and resistance in the USA300 clone of methicillin-resistant Staphylococcus aureus. J. Infect. Dis. 197, 1523-1530 (2008).
91. Wang CH, Lin CY, Luo YH et al. Effects of oligopeptide permease in group a streptococcal infection. Infect. Immun. 73, 2881-2890 (2005).
92. Montgomery CP, Boyle-Vavra S, Daum RS. The arginine catabolic mobile element is not associated with enhanced virulence in experimental invasive disease caused by the community-associated methicillin-resistant Staphylococcus aureus USA300 genetic background. Infect. Immun. 77, 2650-2656 (2009).
93. Bartels MD, Hansen LH, Boye K, Sorensen SJ, Westh H. An unexpected location of the arginine catabolic mobile element (ACME) in a USA300-related MRSA strain. Plos One 6, e16193 (2011).
94. Shore AC, Rossney AS, Brennan OM et al. Characterization of a novel arginine catabolic mobile element (ACME) and staphylococcal chromosomal cassette mec composite island with significant homology to Staphylococcus epidermidis ACME type II in methicillinresistant Staphylococcus aureus genotype ST22-MRSA-IV. Antimicrob. Agents Chemother. 55, 1896-1905 (2011).
95. Urushibara N, Kawaguchiya M, Kobayashi N. Two novel arginine catabolic mobile elements and staphylococcal chromosome cassette mec composite islands in communityacquired methicillin-resistant Staphylococcus aureus genotypes ST5-MRSA-V and ST5-MRSA-II. J. Antimicrob. Chemother. 67(8), 1828-1834 (2012).
96. Mine Y, Higuchi W, Taira K et al. Nosocomial outbreak of multidrug-resistant USA300 methicillin-resistant Staphylococcus aureus causing severe furuncles and carbuncles in Japan. J. Dermatol. 38(12), 1167-1171 (2011).
97. Hu DL, Maina EK, Omoe K, Inoue F, Yasujima M, Nakane A. Superantigenic toxin genes coexist with specific staphylococcal cassette chromosome mec genes in methicillin-resistant Staphylococcus aureus. Tohoku J. Exp. Med. 225, 161-169 (2011).
98. Schijffelen MJ, Boel CH, van Strijp JA, Fluit AC. Whole genome analysis of a livestockassociated methicillin-resistant Staphylococcus aureus ST398 isolate from a case of human endocarditis. BMC Genomics 11, 376 (2010).
99. Fournier B, Hooper DC. A new twocomponent regulatory system involved in adhesion, autolysis, and extracellular proteolytic activity of Staphylococcus aureus. J. Bacteriol. 182, 3955-3964 (2000).
100. Kuroda M, Kuroda H, Oshima T, Takeuchi F, Mori H, Hiramatsu K. Two-component system VraSR positively modulates the regulation of cell-wall biosynthesis pathway in Staphylococcus aureus. Mol. Microbiol. 49, 807-821 (2003).
101. Novick RP. Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol. Microbiol. 48, 1429-1449 (2003).
102. Zhang L, Gray L, Novick RP, Ji G. Transmembrane topology of AgrB, the protein involved in the post-translational modification of AgrD in Staphylococcus aureus. J. Biol. Chem. 277, 34736-34742 (2002).
103. Tsuji BT, Rybak MJ, Lau KL, Sakoulas G. Evaluation of accessory gene regulator (agr) group and function in the proclivity towards vancomycin intermediate resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 51, 1089-1091 (2007).
104. Genestier AL, Michallet MC, Prévost G et al. Staphylococcus aureus Panton-Valentine leukocidin directly targets mitochondria and induces Bax-independent apoptosis of human neutrophils. J. Clin. Invest. 115, 3117-3127 (2005).
105. Cheung GY, Wang R, Khan BA, Sturdevant DE, Otto M. Role of the accessory gene regulator agr in community-associated methicillin-resistant Staphylococcus aureus pathogenesis. Infect. Immun. 79, 1927-1935 (2011).
106. Wirtz C, Witte W, Wolz C, Goerke C. Transcription of the phage-encoded Panton-Valentine leukocidin of Staphylococcus aureus is dependent on the phage life-cycle and on the host background. Microbiology 155, 3491-3499 (2009).
107. Montgomery CP, Boyle-Vavra S, Daum RS. Importance of the global regulators Agr and SaeRS in the pathogenesis of CA-MRSA USA300 infection. Plos One 5, e15177 (2010).
108. Coelho LR, Souza RR, Ferreira FA, Guimaraes MA, Ferreira-Carvalho BT, Figueiredo AM. agr RNAIII divergently regulates glucose-induced biofilm formation in clinical isolates of Staphylococcus aureus. Microbiology 154, 3480-3490 (2008).
109. Grinholc M, Wegrzyn G, Kurlenda J. Evaluation of biofilm production and prevalence of the icaD gene in methicillinresistant and methicillin-susceptible Staphylococcus aureus strains isolated from patients with nosocomial infections and carriers. FEMS Immunol. Med. Microbiol. 50, 375-379 (2007).
110. Bordi C, de Bentzmann S. Hacking into bacterial biofilms: A new therapeutic challenge. Ann. Intensive Care 1(1), 19 (2011).
111. Beenken KE, Mrak LN, Griffin LM et al. Epistatic relationships between sarA and agr in Staphylococcus aureus biofilm formation. Plos One 5, e10790 (2010).
112. von Eiff C. Staphylococcus aureus small colony variants: A challenge to microbiologists and clinicians. Int. J. Antimicrob. Agents 31, 507-510 (2008).
113. Lannergård J, von Eiff C, Sander G et al. Identification of the genetic basis for clinical menadione-auxotrophic small-colony variant isolates of Staphylococcus aureus. Antimicrob. Agents Chemother. 52, 4017-4022 (2008).
114. Mitchell G, Seguin DL, Asselin AE et al. Staphylococcus aureus sigma B-dependent emergence of small-colony variants and biofilm production following exposure to Pseudomonas aeruginosa 4-hydroxy-2-heptylquinoline-N-oxide. BMC Microbiol. 10, 33 (2010).
115. Cuirolo A, Plata K, Rosato AE. Development of homogeneous expression of resistance in methicillin-resistant Staphylococcus aureus clinical strains is functionally associated with a beta-lactam-mediated SOS response. J. Antimicrob. Chemother. 64, 37-45 (2009).
116. Plata KB, Rosato RR, Rosato AE. Fate of mutation rate depends on agr-locus expression during oxacillin-mediated heterogeneous-homogeneous selection in MRSA clinical strains. Antimicrob. Agents Chemother. 55(7), 3176-3186 (2011).
117. Boles BR, Horswill AR. Agr-mediated dispersal of Staphylococcus aureus biofilms. Plos Pathog. 4, e1000052 (2008).
118. Campoccia D, Baldassarri L, Pirini V, Ravaioli S, Montanaro L, Arciola CR. Molecular epidemiology of Staphylococcus aureus from implant orthopaedic infections: Ribotypes, agr polymorphism, leukocidal toxins and antibiotic resistance. Biomaterials 29, 4108-4116 (2008).
119. Nichol KA, Adam HJ, Hussain Z et al. Comparison of community-associated and health care-associated methicillin-resistant Staphylococcus aureus in Canada: Results of the CANWARD 2007-2009 study. Diagn. Microbiol. Infect. Dis. 69, 320-325 (2011).
120. 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. 49, 366-379 (2005).
121. Kuroda H, Kuroda M, Cui L, Hiramatsu K. Subinhibitory concentrations of beta-lactam induce haemolytic activity in Staphylococcus aureus through the SaeRS two-component system. FEMS Microbiol. Lett. 268, 98-105 (2007).
122. Voyich JM, Vuong C, DeWald M et al. The SaeRS gene regulatory system is essential for innate immune evasion by Staphylococcus aureus. J. Infect. Dis. 199, 1698-1706 (2009).
123. Boyle-Vavra S, Yin S, Daum RS. The VraS/ VraR two-component regulatory system required for oxacillin resistance in community-acquired methicillin-resistant Staphylococcus aureus. FEMS Microbiol. Lett. 262, 163-171 (2006).
124. Yin S, Daum RS, Boyle-Vavra S. VraSR two-component regulatory system and its role in induction of pbp2 and vraSR expression by cell wall antimicrobials in Staphylococcus aureus. Antimicrob. Agents Chemother. 50, 336-343 (2006).
125. Bernal P, Lemaire S, Pinho MG, Mobashery S, Hinds J, Taylor PW. Insertion of epicatechin gallate into the cytoplasmic membrane of methicillin-resistant Staphylococcus aureus disrupts penicillinbinding protein (PBP) 2a-mediated beta-lactam resistance by delocalizing PBP2. J. Biol. Chem. 285, 24055-24065 (2010).
126. Stapleton PD, Shah S, Ehlert K, Hara Y, Taylor PW. The beta-lactam-resistance modifier (-)-epicatechin gallate alters the architecture of the cell wall of Staphylococcus aureus. Microbiology 153, 2093-2103 (2007).
127. Hatano T, Kusuda M, Inada K et al. Effects of tannins and related polyphenols on methicillin-resistant Staphylococcus aureus. Phytochemistry 66, 2047-2055 (2005).
128. Shiota S, Shimizu M, Sugiyama J, Morita Y, Mizushima T, Tsuchiya T. Mechanisms of action of corilagin and tellimagrandin I that remarkably potentiate the activity of beta-lactams against methicillin-resistant Staphylococcus aureus. Microbiol. Immunol. 48, 67-73 (2004).
129. Hou Z, Zhou Y, Wang HF et al. Co-blockade of mecR1/blaR1 signal pathway to restore antibiotic susceptibility in clinical isolates of methicillin-resistant Staphylococcus aureus. Arch. Med. Sci. 7, 414-422 (2011).
130. Balaban N, Cirioni O, Giacometti A et al. Treatment of Staphylococcus aureus biofilm infection by the quorum-sensing inhibitor RIP. Antimicrob. Agents Chemother. 51, 2226-2229 (2007).
131. International Working Group on the Classification of Staphylococcal Cassette Chromosome Elements (IWG-SCC). Classification of staphylococcal cassette chromosome mec (SCCmec): Guidelines for reporting novel SCCmec elements. Antimicrob. Agents Chemother. 53, 4961-4967 (2009).
132. Chlebowicz MA, Nganou K, Kozytska S et al. Recombination between ccrC genes in a type V (5C2&5) staphylococcal cassette chromosome mec (SCCmec) of Staphylococcus aureus ST398 leads to conversion from methicillin resistance to methicillin susceptibility in vivo. Antimicrob. Agents Chemother. 54, 783-791 (2010).