Characterisation of a novel SCCmec VI element harbouring fusC in an emerging Staphylococcus aureus strain from the Arabian Gulf region

Autoři: Abiola Senok aff001;  Peter Slickers aff002;  Helmut Hotzel aff004;  Samar Boswihi aff005;  Sascha D. Braun aff002;  Darius Gawlik aff007;  Elke Müller aff002;  Anju Nabi aff008;  Rania Nassar aff001;  Hedda Nitschke aff009;  Annett Reissig aff002;  Antje Ruppelt-Lorz aff010;  Joseph Mafofo aff011;  Ali M. Somily aff012;  Edet Udo aff005;  Ralf Ehricht aff002;  Stefan Monecke aff002
Působiště autorů: College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates aff001;  InfectoGnostics Research Campus Jena, Jena, Germany aff002;  Abbott (Alere Technologies GmbH), Jena, Germany aff003;  Friedrich-Loeffler-Institut (Federal Research Institute for Animal Health), Institute of Bacterial Infections and Zoonoses, Jena, Germany aff004;  Department of Microbiology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait aff005;  Leibniz Institute of Photonic Technology (IPHT), Jena, Germany aff006;  PTC - Phage Technology Center GmbH, Bönen, Germany aff007;  Microbiology & Infection Control Unit, Pathology Department, Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates aff008;  Department of Laboratory Medicine, Hospital Dresden-Neustadt, Dresden, Germany aff009;  Institute for Medical Microbiology and Hygiene, Medical Faculty "Carl Gustav Carus", Technische Universität Dresden, Dresden, Germany aff010;  Agiomix FZ-LLC, Dubai Science Park Warehouse Complex, Dubai, United Arab Emirates aff011;  Department of Pathology and Laboratory Medicine, College of Medicine, King Khalid University Hospital and King Saud University, Riyadh, Saudi Arabia aff012
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223985


Fusidic acid is a steroid antibiotic known since the 1960s. It is frequently used in topical preparations, i.e., ointments, for the treatment of skin and soft tissue infections caused by Staphylococcus aureus. There is an increasing number of methicillin-resistant S. aureus (MRSA) strains that harbour plasmid-borne fusB/far1 or fusC that is localised on SCC elements. In this study we examined a series of related CC30-MRSA isolates from the Arabian Gulf countries that presented with SCCmec elements and fusC, including a variant that—to the best of our knowledge—has not yet formally been described. It consisted of a class B mec complex and ccrA/B-4 genes. The fusidic acid resistance gene fusC was present, but contrary to the previously sequenced element of HDE288, it was not accompanied by tirS. This element was identified in CC30 MRSA from Kuwait, Saudi Arabia and the United Arab Emirates that usually also harbour the Panton-Valentin leukocidin (PVL) genes. It was also identified in CC8 and ST834 isolates. In addition, further CC30 MRSA strains with other SCCmec VI elements harbouring fusC were found to circulate in the Arabian Gulf region. It can be assumed that MRSA strains with SCCmec elements that include fusC have a selective advantage in both hospital and community settings warranting a review of the use of topical antibiotics and indicating the necessity of reducing over-the-counter sale of antibiotics, including fusidic acid, without prescription.

Klíčová slova:

Antibiotics – Antimicrobial resistance – Genetic elements – Methicillin-resistant Staphylococcus aureus – Sequence databases – Staphylococcus – Staphylococcus aureus – Saudi Arabia


1. Jevons MP. "Celbenin"-resistant Staphylococci. British Medical Journal. 1961;1(5219):1924–5.

2. Monecke S, Muller E, Schwarz S, Hotzel H, Ehricht R. Rapid microarray based identification of different mecA alleles in Staphylococci. Antimicrob Agents Chemother. 2012;56(11):5547–54. Epub 2012/08/15. doi: 10.1128/AAC.00574-12 22890767.

3. Becker K, Ballhausen B, Köck R, Kriegeskorte A. Methicillin resistance in Staphylococcus isolates: The “mec alphabet” with specific consideration of mecC, a mec homolog associated with zoonotic S. aureus lineages. Int J Med Microbiol. 2014;304(7):794–804. doi: 10.1016/j.ijmm.2014.06.007 25034857

4. Ito T, Katayama Y, Asada K, Mori N, Tsutsumimoto K, Tiensasitorn C, et al. Structural comparison of three types of staphylococcal cassette chromosome mec integrated in the chromosome in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2001;45(5):1323–36. doi: 10.1128/AAC.45.5.1323-1336.2001 11302791.

5. 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. 1999;43(6):1449–58. 10348769.

6. 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. 2004;48(7):2637–51. doi: 10.1128/AAC.48.7.2637-2651.2004 15215121.

7. Ito T, Okuma K, Ma XX, Yuzawa H, Hiramatsu K. Insights on antibiotic resistance of Staphylococcus aureus from its whole genome: genomic island SCC. Drug Resist Updat. 2003;6(1):41–52. 12654286.

8. IWG- SCC. Classification of staphylococcal cassette chromosome mec (SCCmec): guidelines for reporting novel SCCmec elements. Antimicrob Agents Chemother. 2009;53(12):4961–7. doi: 10.1128/AAC.00579-09 19721075.

9. Monecke S, Jatzwauk L, Muller E, Nitschke H, Pfohl K, Slickers P, et al. Diversity of SCCmec elements in Staphylococcus aureus as observed in South-Eastern Germany. PLoS ONE. 2016;11(9):e0162654. Epub 2016/09/21. doi: 10.1371/journal.pone.0162654 27648947.

10. Shore A, Rossney AS, Keane CT, Enright MC, Coleman DC. Seven novel variants of the staphylococcal chromosomal cassette mec in methicillin-resistant Staphylococcus aureus isolates from Ireland. Antimicrob Agents Chemother. 2005;49(5):2070–83. doi: 10.1128/AAC.49.5.2070-2083.2005 15855533.

11. Shore AC, Coleman DC. Staphylococcal cassette chromosome mec: recent advances and new insights. Int J Med Microbiol. 2013;303(6–7):350–9. doi: 10.1016/j.ijmm.2013.02.002 23499303

12. Ellington MJ, Reuter S, Harris SR, Holden MT, Cartwright EJ, Greaves D, et al. Emergent and evolving antimicrobial resistance cassettes in community-associated fusidic acid and meticillin-resistant Staphylococcus aureus. Int J Antimicrob Agents. 2015;45(5):477–84. Epub 2015/03/15. doi: 10.1016/j.ijantimicag.2015.01.009 25769787.

13. Oliveira DC, Milheirico C, de Lencastre H. Redefining a structural variant of staphylococcal cassette chromosome mec, SCCmec type VI. Antimicrob Agents Chemother. 2006;50(10):3457–9. doi: 10.1128/AAC.00629-06 17005831

14. Williamson DA, Carter GP, Howden BP. Current and Emerging Topical Antibacterials and Antiseptics: Agents, Action, and Resistance Patterns. Clinical microbiology reviews. 2017;30(3):827–60. Epub 2017/06/07. doi: 10.1128/CMR.00112-16 28592405.

15. Schofer H, Simonsen L. Fusidic acid in dermatology: an updated review. Eur J Dermatol. 2010;20(1):6–15. Epub 2009/12/17. doi: 10.1684/ejd.2010.0833 20007058.

16. Turnidge J, Collignon P. Resistance to fusidic acid. Int J Antimicrob Agents. 1999;12 Suppl 2:S35–44. Epub 1999/10/21. doi: 10.1016/s0924-8579(98)00072-7 10528785.

17. Farrell DJ, Castanheira M, Chopra I. Characterization of Global Patterns and the Genetics of Fusidic Acid Resistance. Clinical Infectious Diseases. 2011;52(suppl_7):S487–S92. doi: 10.1093/cid/cir164 21546625

18. Lannergård J, Cao S, Norström T, Delgado A, Gustafson JE, Hughes D. Genetic Complexity of Fusidic Acid-Resistant Small Colony Variants (SCV) in Staphylococcus aureus. PLOS ONE. 2011;6(11):e28366. doi: 10.1371/journal.pone.0028366 22140579

19. Monecke S, Slickers P, Hotzel H, Richter-Huhn G, Pohle M, Weber S, et al. Microarray-based characterisation of a Panton-Valentine leukocidin-positive community-acquired strain of methicillin-resistant Staphylococcus aureus. Clin Microbiol Infect. 2006;12(8):718–28. doi: 10.1111/j.1469-0691.2006.01420.x 16842566

20. Aires de Sousa M, Bartzavali C, Spiliopoulou I, Sanches IS, Crisostomo MI, de Lencastre H. Two international methicillin-resistant Staphylococcus aureus clones endemic in a university hospital in Patras, Greece. J Clin Microbiol. 2003;41(5):2027–32. doi: 10.1128/JCM.41.5.2027-2032.2003 12734244.

21. Basset P, Amhis W, Blanc DS. Changing molecular epidemiology of methicillin-resistant Staphylococcus aureus in an Algerian hospital. J Infect Dev Ctries. 2015;9(2):206–9. Epub 2015/02/24. doi: 10.3855/jidc.4620 25699496.

22. Ben Slama K, Gharsa H, Klibi N, Jouini A, Lozano C, Gomez-Sanz E, et al. Nasal carriage of Staphylococcus aureus in healthy humans with different levels of contact with animals in Tunisia: genetic lineages, methicillin resistance, and virulence factors. Eur J Clin Microbiol Infect Dis. 2011;30(4):499–508. Epub 2010/11/16. doi: 10.1007/s10096-010-1109-6 21076928.

23. Boswihi SS, Udo EE, Al-Sweih N. Shifts in the Clonal Distribution of Methicillin-Resistant Staphylococcus aureus in Kuwait Hospitals: 1992–2010. PLoS ONE. 2016;11(9):e0162744. doi: 10.1371/journal.pone.0162744 27631623

24. Tokajian ST, Khalil PA, Jabbour D, Rizk M, Farah MJ, Hashwa FA, et al. Molecular characterization of Staphylococcus aureus in Lebanon. Epidemiol Infect. 2010;138(5):707–12. doi: 10.1017/S0950268810000440 20202283.

25. Udo EE, Sarkhoo E. Genetic analysis of high-level mupirocin resistance in the ST80 clone of community-associated meticillin-resistant Staphylococcus aureus. J Med Microbiol. 2010;59(Pt 2):193–9. doi: 10.1099/jmm.0.013268-0 19833783.

26. Vourli S, Perimeni D, Makri A, Polemis M, Voyiatzi A, Vatopoulos A. Community acquired MRSA infections in a paediatric population in Greece. Euro Surveill. 2005;10(5):78–9. 16077207.

27. Holden MTG, Feil EJ, Lindsay JA, Peacock SJ, Day NPJ, Enright MC, et al. Complete genomes of two clinical Staphylococcus aureus strains: Evidence for the rapid evolution of virulence and drug resistance. PNAS. 2004;101(26):9786–91. doi: 10.1073/pnas.0402521101 15213324

28. Patot S, Rc Imbert P, Baude J, Martins Simões P, Campergue J-B, Louche A, et al. The TIR Homologue Lies near Resistance Genes in Staphylococcus aureus, Coupling Modulation of Virulence and Antimicrobial Susceptibility. PLOS Pathogens. 2017;13(1):e1006092. doi: 10.1371/journal.ppat.1006092 28060920

29. Williamson DA, Monecke S, Heffernan H, Ritchie SR, Roberts SA, Upton A, et al. High usage of topical fusidic acid and rapid clonal expansion of fusidic acid-resistant Staphylococcus aureus: a cautionary tale. Clin Infect Dis. 2014;59(10):1451–4. Epub 2014/08/21. doi: 10.1093/cid/ciu658 25139961.

30. Boswihi SS, Udo EE, Monecke S, Mathew B, Noronha B, Verghese T, et al. Emerging variants of methicillin-resistant Staphylococcus aureus genotypes in Kuwait hospitals. PLoS One. 2018;13(4):e0195933. Epub 2018/04/19. doi: 10.1371/journal.pone.0195933 29668723.

31. Monecke S, Muller E, Buechler J, Rejman J, Stieber B, Akpaka PE, et al. Rapid detection of Panton-Valentine leukocidin in Staphylococcus aureus cultures by use of a lateral flow assay based on monoclonal antibodies. J Clin Microbiol. 2013;51(2):487–95. Epub 2012/11/24. doi: 10.1128/JCM.02285-12 23175260.

32. Monecke S, Coombs G, Shore AC, Coleman DC, Akpaka P, Borg M, et al. A field guide to pandemic, epidemic and sporadic clones of methicillin-resistant Staphylococcus aureus. PLoS One. 2011;6(4):e17936. doi: 10.1371/journal.pone.0017936 21494333

33. Monecke S, Slickers P, Ehricht R. Assignment of Staphylococcus aureus isolates to clonal complexes based on microarray analysis and pattern recognition. FEMS Immunol Med Microbiol. 2008;53:237–51. doi: 10.1111/j.1574-695X.2008.00426.x 18507678

34. Monecke S, Nitschke H, Slickers P, Ehricht R, Swanston W, Manjunath M, et al. Molecular epidemiology and characterisation of MRSA isolates from Trinidad and Tobago. Eur J Clin Microbiol Infect Dis. 2012;31(7):1497–500. Epub 2011/11/10. doi: 10.1007/s10096-011-1469-6 22068275.

35. Monecke S, Ruppelt-Lorz A, Muller E, Reissig A, Thurmer A, Shore AC, et al. Dissemination of high-level mupirocin-resistant CC22-MRSA-IV in Saxony. GMS Hyg Infect Control. 2017;12:Doc19. Epub 2017/12/01. doi: 10.3205/dgkh000304 29184755.

36. Dawkins R. Das egoistische Gen (The selfish gene, German ed.). Heidelberg: Spektrum Verlag; 1994.

37. Dauwalder O, Lina G, Durand G, Bes M, Meugnier H, Jarlier V, et al. Epidemiology of invasive methicillin-resistant Staphylococcus aureus clones collected in France in 2006 and 2007. J Clin Microbiol. 2008;46(10):3454–8. doi: 10.1128/JCM.01050-08 18667599.

38. Kinnevey PM, Shore AC, Brennan GI, Sullivan DJ, Ehricht R, Monecke S, et al. Emergence of sequence type 779 methicillin-resistant Staphylococcus aureus harboring a novel pseudo staphylococcal cassette chromosome mec (SCCmec)-SCC-SCCCRISPR composite element in Irish hospitals. Antimicrob Agents Chemother. 2013;57(1):524–31. Epub 2012/11/14. doi: 10.1128/AAC.01689-12 23147725.

39. Monecke S, Skakni L, Hasan R, Ruppelt A, Ghazal SS, Hakawi A, et al. Characterisation of MRSA strains isolated from patients in a hospital in Riyadh, Kingdom of Saudi Arabia. BMC Microbiol. 2012;12(1):146. Epub 2012/07/25. doi: 10.1186/1471-2180-12-146 22823982.

40. Scerri J, Monecke S, Borg MA. Prevalence and characteristics of community carriage of methicillin-resistant Staphylococcus aureus in Malta. J Epidemiol Glob Health. 2013;3(3):165–73. Epub 2013/08/13. doi: 10.1016/j.jegh.2013.05.003 23932059.

41. Senok A, Ehricht R, Monecke S, Al-Saedan R, Somily A. Molecular characterization of methicillin-resistant Staphylococcus aureus in nosocomial infections in a tertiary-care facility: emergence of new clonal complexes in Saudi Arabia. New Microbes New Infect. 2016;14:13–8. Epub 2016/09/14. doi: 10.1016/j.nmni.2016.07.009 27621823.

42. Senok AC, Somily AM, Slickers P, Raji MA, Garaween G, Shibl A, et al. Investigating a rare methicillin-resistant Staphylococcus aureus strain: first description of genome sequencing and molecular characterization of CC15-MRSA. Infect Drug Resist. 2017;10:307–15. Epub 2017/10/19. doi: 10.2147/IDR.S145394 29042801.

Článek vyšel v časopise


2019 Číslo 11