No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

Staphylococci: Evolving Genomes

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • Author: Jodi A. Lindsay1
  • Editors: Vincent A. Fischetti2, Richard P. Novick3, Joseph J. Ferretti4, Daniel A. Portnoy5, Miriam Braunstein6, Julian I. Rood7
    Affiliations: 1: St. George’s, University of London, Institute of Infection and Immunity, London, United Kingdom; 2: The Rockefeller University, New York, NY; 3: Skirball Institute for Molecular Medicine, NYU Medical Center, New York, NY; 4: Department of Microbiology & Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK; 5: Department of Molecular and Cellular Microbiology, University of California, Berkeley, Berkeley, CA; 6: Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, NC; 7: Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
  • Source: microbiolspec November 2019 vol. 7 no. 6 doi:10.1128/microbiolspec.GPP3-0071-2019
  • Received 02 June 2019 Accepted 04 June 2019 Published 25 November 2019
  • Jodi A. Lindsay, [email protected]
image of Staphylococci: Evolving Genomes
    Preview this microbiology spectrum article:
    Zoom in

    Staphylococci: Evolving Genomes, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/7/6/GPP3-0071-2019-1.gif /docserver/preview/fulltext/microbiolspec/7/6/GPP3-0071-2019-2.gif
  • Abstract:

    Staphylococci, and in particular , cause an extensive variety of infections in a range of hosts. The comprehensive analysis of staphylococcal genomes reveals mechanisms controlling the organism’s biology, pathobiology, and dissemination. Whole-genome sequencing technologies led to a quantum leap in our understanding of bacterial genomes. The recent cost reduction of sequencing has resulted in unprecedented volumes of genomic information about , one of the most sequenced bacterial species. Collecting, comparing, and interpreting big data is challenging, but fascinating insights have emerged. For example, it is becoming clearer which selective pressures staphylococci face in their habitats and which mechanisms allow this pathogen to adapt, survive, and spread. A key theme is the constant evolution of staphylococci as they alter their genome, exchange DNA, and adapt to new environments, leading to the emergence of increasingly successful, antibiotic-resistant, immune-evading, and host-adapted colonizers and pathogens. This article introduces the structure of staphylococcal genomes, details how genomes vary between strains, outlines the mechanisms of genetic variation, and describes the features of successful clones.

  • Citation: Lindsay J. 2019. Staphylococci: Evolving Genomes. Microbiol Spectrum 7(6):GPP3-0071-2019. doi:10.1128/microbiolspec.GPP3-0071-2019.


1. Holden MTG, Lindsay JA. 2008. Whole genomes: sequence, microarray, and systems biology, p 1–28. In Lindsay JA (ed), Staphylococcus: Molecular Genetics. Caister Academic Press, Norfolk, United Kingdom.
2. Kuroda M, Ohta T, Uchiyama I, Baba T, Yuzawa H, Kobayashi I, Cui L, Oguchi A, Aoki K, Nagai Y, Lian J, Ito T, Kanamori M, Matsumaru H, Maruyama A, Murakami H, Hosoyama A, Mizutani-Ui Y, Takahashi NK, Sawano T, Inoue R, Kaito C, Sekimizu K, Hirakawa H, Kuhara S, Goto S, Yabuzaki J, Kanehisa M, Yamashita A, Oshima K, Furuya K, Yoshino C, Shiba T, Hattori M, Ogasawara N, Hayashi H, Hiramatsu K. 2001. Whole genome sequencing of meticillin-resistant Staphylococcus aureus. Lancet 357:1225–1240 http://dx.doi.org/10.1016/S0140-6736(00)04403-2.
3. Baba T, Takeuchi F, Kuroda M, Yuzawa H, Aoki K, Oguchi A, Nagai Y, Iwama N, Asano K, Naimi T, Kuroda H, Cui L, Yamamoto K, Hiramatsu K. 2002. Genome and virulence determinants of high virulence community-acquired MRSA. Lancet 359:1819–1827 http://dx.doi.org/10.1016/S0140-6736(02)08713-5.
4. Holden MTG, Feil EJ, Lindsay JA, Peacock SJ, Day NP, Enright MC, Foster TJ, Moore CE, Hurst L, Atkin R, Barron A, Bason N, Bentley SD, Chillingworth C, Chillingworth T, Churcher C, Clark L, Corton C, Cronin A, Doggett J, Dowd L, Feltwell T, Hance Z, Harris B, Hauser H, Holroyd S, Jagels K, James KD, Lennard N, Line A, Mayes R, Moule S, Mungall K, Ormond D, Quail MA, Rabbinowitsch E, Rutherford K, Sanders M, Sharp S, Simmonds M, Stevens K, Whitehead S, Barrell BG, Spratt BG, Parkhill J. 2004. 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 http://dx.doi.org/10.1073/pnas.0402521101. [PubMed]
5. Gillaspy AF, Worrell V, Roe BA, Dyer DW, Orvis J, Iandolo JJ. 2006. The Staphylococcus aureus NCTC 8325 genome, p 381–412. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, 2nd ed. ASM Press, Washington, DC. http://dx.doi.org/10.1128/9781555816513.ch32
6. Gill SR, Fouts DE, Archer GL, Mongodin EF, Deboy RT, Ravel J, Paulsen IT, Kolonay JF, Brinkac L, Beanan M, Dodson RJ, Daugherty SC, Madupu R, Angiuoli SV, Durkin AS, Haft DH, Vamathevan J, Khouri H, Utterback T, Lee C, Dimitrov G, Jiang L, Qin H, Weidman J, Tran K, Kang K, Hance IR, Nelson KE, Fraser CM. 2005. Insights on evolution of virulence and resistance from the complete genome analysis of an early methicillin-resistant Staphylococcus aureus strain and a biofilm-producing methicillin-resistant Staphylococcus epidermidis strain. J Bacteriol 187:2426–2438 http://dx.doi.org/10.1128/JB.187.7.2426-2438.2005. [PubMed]
7. Lindsay JA, Holden MTG. 2004. Staphylococcus aureus: superbug, super genome? Trends Microbiol 12:378–385 http://dx.doi.org/10.1016/j.tim.2004.06.004. [PubMed]
8. Grundmann H, Aires-de-Sousa M, Boyce J, Tiemersma E. 2006. Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat. Lancet 368:874–885 http://dx.doi.org/10.1016/S0140-6736(06)68853-3.
9. DeLeo FR, Chambers HF. 2009. Reemergence of antibiotic-resistant Staphylococcus aureus in the genomics era. J Clin Invest 119:2464–2474 http://dx.doi.org/10.1172/JCI38226. [PubMed]
10. Sollid JUE, Furberg AS, Hanssen AM, Johannessen M. 2014. Staphylococcus aureus: determinants of human carriage. Infect Genet Evol 21:531–541 http://dx.doi.org/10.1016/j.meegid.2013.03.020. [PubMed]
11. Wertheim HF, Melles DC, Vos MC, van Leeuwen W, van Belkum A, Verbrugh HA, Nouwen JL. 2005. The role of nasal carriage in Staphylococcus aureus infections. Lancet Infect Dis 5:751–762 http://dx.doi.org/10.1016/S1473-3099(05)70295-4.
12. von Eiff C, Becker K, Machka K, Stammer H, Peters G. 2001. Nasal carriage as a source of Staphylococcus aureus bacteremia. N Engl J Med 344:11–16 http://dx.doi.org/10.1056/NEJM200101043440102. [PubMed]
13. Krebes J, Al-Ghusein H, Feasey N, Breathnach A, Lindsay JA. 2011. Are nasal carriers of Staphylococcus aureus more likely to become colonized or infected with methicillin-resistant Staphylococcus aureus on admission to a hospital? J Clin Microbiol 49:430–432 http://dx.doi.org/10.1128/JCM.02039-10. [PubMed]
14. Sung JML, Lloyd DH, Lindsay JA. 2008. Staphylococcus aureus host specificity: comparative genomics of human versus animal isolates by multi-strain microarray. Microbiology 154:1949–1959 http://dx.doi.org/10.1099/mic.0.2007/015289-0. [PubMed]
15. Harkins CP, Pichon B, Doumith M, Parkhill J, Westh H, Tomasz A, de Lencastre H, Bentley SD, Kearns AM, Holden MTG. 2017. Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice. Genome Biol 18:130 http://dx.doi.org/10.1186/s13059-017-1252-9. [PubMed]
16. WHO. 2014. Antimicrobial resistance. Global report on surveillance. World Health Organization, Geneva, Switzerland. https://who.int/drugresistance/documents/surveillancereport/en/.
17. Johnson AP, Pearson A, Duckworth G. 2005. Surveillance and epidemiology of MRSA bacteraemia in the UK. J Antimicrob Chemother 56:455–462 http://dx.doi.org/10.1093/jac/dki266. [PubMed]
18. Graveland H, Duim B, van Duijkeren E, Heederik D, Wagenaar JA. 2011. Livestock-associated methicillin-resistant Staphylococcus aureus in animals and humans. Int J Med Microbiol 301:630–634 http://dx.doi.org/10.1016/j.ijmm.2011.09.004. [PubMed]
19. Queck SY, Otto M. 2008. Staphylococcus epidermidis and other coagulase-negative staphylococci, p 227–254. In Lindsay J (ed), Staphylococcus: Molecular Genetics. Caister Academic Press, Norfolk, United Kingdom.
20. Sakinc T, Kleine B, Gatermann SG. 2006. SdrI, a serine-aspartate repeat protein identified in Staphylococcus saprophyticus strain 7108, is a collagen-binding protein. Infect Immun 74:4615–4623 http://dx.doi.org/10.1128/IAI.01885-05. [PubMed]
21. Vandenesch F, Eykyn SJ, Etienne J, Lemozy J. 1995. Skin and post-surgical wound infections due to Staphylococcus lugdunensis. Clin Microbiol Infect 1:73–74 http://dx.doi.org/10.1111/j.1469-0691.1995.tb00449.x. [PubMed]
22. Tong SYC, Sharma-Kuinkel BK, Thaden JT, Whitney AR, Yang SJ, Mishra NN, Rude T, Lilliebridge RA, Selim MA, Ahn SH, Holt DC, Giffard PM, Bayer AS, Deleo FR, Fowler VG Jr. 2013. Virulence of endemic nonpigmented northern Australian Staphylococcus aureus clone (clonal complex 75, S. argenteus) is not augmented by staphyloxanthin. J Infect Dis 208:520–527 http://dx.doi.org/10.1093/infdis/jit173. [PubMed]
23. Guinane CM, Ben Zakour NL, Tormo-Mas MA, Weinert LA, Lowder BV, Cartwright RA, Smyth DS, Smyth CJ, Lindsay JA, Gould KA, Witney A, Hinds J, Bollback JP, Rambaut A, Penadés JR, Fitzgerald JR. 2010. Evolutionary genomics of Staphylococcus aureus reveals insights into the origin and molecular basis of ruminant host adaptation. Genome Biol Evol 2:454–466 http://dx.doi.org/10.1093/gbe/evq031. [PubMed]
24. McCarthy AJ, Harrison EM, Stanczak-Mrozek K, Leggett B, Waller A, Holmes MA, Lloyd DH, Lindsay JA, Loeffler A. 2015. Genomic insights into the rapid emergence and evolution of MDR in Staphylococcus pseudintermedius. J Antimicrob Chemother 70:997–1007.
25. Fitzgerald JR, Penadés JR. 2008. Staphylococci of animals, p 255–269. In Lindsay J (ed), Staphylococcus: Molecular Genetics. Caister Academic Press, Norfolk, United Kingdom.
26. Petit RA III, Read TD. 2018. Staphylococcus aureus viewed from the perspective of 40,000+ genomes. PeerJ 6:e5261 http://dx.doi.org/10.7717/peerj.5261. [PubMed]
27. Naushad S, Barkema HW, Luby C, Condas LAZ, Nobrega DB, Carson DA, De Buck J. 2016. Comprehensive phylogenetic analysis of bovine non-aureus staphylococci species based on whole-genome sequencing. Front Microbiol 7:1990 http://dx.doi.org/10.3389/fmicb.2016.01990. [PubMed]
28. Fuchs S, Mehlan H, Bernhardt J, Hennig A, Michalik S, Surmann K, Pané-Farré J, Giese A, Weiss S, Backert L, Herbig A, Nieselt K, Hecker M, Völker U, Mäder U. 2018. AureoWiki: the repository of the Staphylococcus aureus research and annotation community. Int J Med Microbiol 308:558–568 http://dx.doi.org/10.1016/j.ijmm.2017.11.011. [PubMed]
29. Carver TJ, Rutherford KM, Berriman M, Rajandream MA, Barrell BG, Parkhill J. 2005. ACT: the Artemis comparison tool. Bioinformatics 21:3422–3423 http://dx.doi.org/10.1093/bioinformatics/bti553. [PubMed]
30. Ding W, Baumdicker F, Neher RA. 2018. panX: pan-genome analysis and exploration. Nucleic Acids Res 46:e5 http://dx.doi.org/10.1093/nar/gkx977. [PubMed]
31. Sassi M, Augagneur Y, Mauro T, Ivain L, Chabelskaya S, Hallier M, Sallou O, Felden B. 2015. SRD: a Staphylococcus regulatory RNA database. RNA 21:1005–1017 http://dx.doi.org/10.1261/rna.049346.114. [PubMed]
32. Bradley P, Gordon NC, Walker TM, Dunn L, Heys S, Huang B, Earle S, Pankhurst LJ, Anson L, de Cesare M, Piazza P, Votintseva AA, Golubchik T, Wilson DJ, Wyllie DH, Diel R, Niemann S, Feuerriegel S, Kohl TA, Ismail N, Omar SV, Smith EG, Buck D, McVean G, Walker AS, Peto TEA, Crook DW, Iqbal Z. 2015. Rapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis. Nat Commun 6:10063 http://dx.doi.org/10.1038/ncomms10063.
33. Aanensen DM, Feil EJ, Holden MT, Dordel J, Yeats CA, Fedosejev A, Goater R, Castillo-Ramírez S, Corander J, Colijn C, Chlebowicz MA, Schouls L, Heck M, Pluister G, Ruimy R, Kahlmeter G, Åhman J, Matuschek E, Friedrich AW, Parkhill J, Bentley SD, Spratt BG, Grundmann H, European SRL Working Group. 2016. Whole-genome sequencing for routine pathogen surveillance in public health: a population snapshot of invasive Staphylococcus aureus in Europe. MBio 7:e00444-16 http://dx.doi.org/10.1128/mBio.00444-16. [PubMed]
34. Fey PD, Endres JL, Yajjala VK, Widhelm TJ, Boissy RJ, Bose JL, Bayles KW. 2013. A genetic resource for rapid and comprehensive phenotype screening of nonessential Staphylococcus aureus genes. MBio 4:e00537-12 http://dx.doi.org/10.1128/mBio.00537-12. [PubMed]
35. Bose JL, Fey PD, Bayles KW. 2013. Genetic tools to enhance the study of gene function and regulation in Staphylococcus aureus. Appl Environ Microbiol 79:2218–2224 http://dx.doi.org/10.1128/AEM.00136-13. [PubMed]
36. Harris SR, Feil EJ, Holden MTG, Quail MA, Nickerson EK, Chantratita N, Gardete S, Tavares A, Day N, Lindsay JA, Edgeworth JD, de Lencastre H, Parkhill J, Peacock SJ, Bentley SD. 2010. Evolution of MRSA during hospital transmission and intercontinental spread. Science 327:469–474 http://dx.doi.org/10.1126/science.1182395. [PubMed]
37. Price JR, Cole K, Bexley A, Kostiou V, Eyre DW, Golubchik T, Wilson DJ, Crook DW, Walker AS, Peto TEA, Llewelyn MJ, Paul J, Modernising Medical Microbiology Informatics Group. 2017. Transmission of Staphylococcus aureus between health-care workers, the environment, and patients in an intensive care unit: a longitudinal cohort study based on whole-genome sequencing. Lancet Infect Dis 17:207–214 http://dx.doi.org/10.1016/S1473-3099(16)30413-3.
38. Golubchik T, Batty EM, Miller RR, Farr H, Young BC, Larner-Svensson H, Fung R, Godwin H, Knox K, Votintseva A, Everitt RG, Street T, Cule M, Ip CLC, Didelot X, Peto TEA, Harding RM, Wilson DJ, Crook DW, Bowden R. 2013. Within-host evolution of Staphylococcus aureus during asymptomatic carriage. PLoS One 8:e61319 http://dx.doi.org/10.1371/journal.pone.0061319. [PubMed]
39. Paterson GK, Harrison EM, Murray GGR, Welch JJ, Warland JH, Holden MTG, Morgan FJE, Ba X, Koop G, Harris SR, Maskell DJ, Peacock SJ, Herrtage ME, Parkhill J, Holmes MA. 2015. Capturing the cloud of diversity reveals complexity and heterogeneity of MRSA carriage, infection and transmission. Nat Commun 6:6560 http://dx.doi.org/10.1038/ncomms7560. [PubMed]
40. Canfield GS, Schwingel JM, Foley MH, Vore KL, Boonanantanasarn K, Gill AL, Sutton MD, Gill SR. 2013. Evolution in fast forward: a potential role for mutators in accelerating Staphylococcus aureus pathoadaptation. J Bacteriol 195:615–628 http://dx.doi.org/10.1128/JB.00733-12. [PubMed]
41. Prunier AL, Leclercq R. 2005. Role of mutS and mutL genes in hypermutability and recombination in Staphylococcus aureus. J Bacteriol 187:3455–3464 http://dx.doi.org/10.1128/JB.187.10.3455-3464.2005. [PubMed]
42. Chua KYL, Seemann T, Harrison PF, Monagle S, Korman TM, Johnson PDR, Coombs GW, Howden BO, Davies JK, Howden BP, Stinear TP. 2011. The dominant Australian community-acquired methicillin-resistant Staphylococcus aureus clone ST93-IV [2B] is highly virulent and genetically distinct. PLoS One 6:e25887 http://dx.doi.org/10.1371/journal.pone.0025887. [PubMed]
43. Tong SYC, Holden MTG, Nickerson EK, Cooper BS, Köser CU, Cori A, Jombart T, Cauchemez S, Fraser C, Wuthiekanun V, Thaipadungpanit J, Hongsuwan M, Day NP, Limmathurotsakul D, Parkhill J, Peacock SJ. 2015. Genome sequencing defines phylogeny and spread of methicillin-resistant Staphylococcus aureus in a high transmission setting. Genome Res 25:111–118 http://dx.doi.org/10.1101/gr.174730.114. [PubMed]
44. Lindsay JA, Moore CE, Day NP, Peacock SJ, Witney AA, Stabler RA, Husain SE, Butcher PD, Hinds J. 2006. Microarrays reveal that each of the ten dominant lineages of Staphylococcus aureus has a unique combination of surface-associated and regulatory genes. J Bacteriol 188:669–676 http://dx.doi.org/10.1128/JB.188.2.669-676.2006. [PubMed]
45. Feil EJ, Cooper JE, Grundmann H, Robinson DA, Enright MC, Berendt T, Peacock SJ, Smith JM, Murphy M, Spratt BG, Moore CE, Day NPJ. 2003. How clonal is Staphylococcus aureus? J Bacteriol 185:3307–3316 http://dx.doi.org/10.1128/JB.185.11.3307-3316.2003. [PubMed]
46. McCarthy AJ, Lindsay JA. 2010. Genetic variation in Staphylococcus aureus surface and immune evasion genes is lineage associated: implications for vaccine design and host-pathogen interactions. BMC Microbiol 10:173 http://dx.doi.org/10.1186/1471-2180-10-173. [PubMed]
47. Lindsay JA. 2010. Genomic variation and evolution of Staphylococcus aureus. Int J Med Microbiol 300:98–103 http://dx.doi.org/10.1016/j.ijmm.2009.08.013. [PubMed]
48. McCarthy AJ, Lindsay JA. 2013. Staphylococcus aureus innate immune evasion is lineage-specific: a bioinfomatics study. Infect Genet Evol 19:7–14 http://dx.doi.org/10.1016/j.meegid.2013.06.012. [PubMed]
49. Waldron DE, Lindsay JA. 2006. Sau1: a novel lineage-specific type I restriction-modification system that blocks horizontal gene transfer into Staphylococcus aureus and between S. aureus isolates of different lineages. J Bacteriol 188:5578–5585 http://dx.doi.org/10.1128/JB.00418-06. [PubMed]
50. Roberts GA, Houston PJ, White JH, Chen K, Stephanou AS, Cooper LP, Dryden DTF, Lindsay JA. 2013. Impact of target site distribution for type I restriction enzymes on the evolution of methicillin-resistant Staphylococcus aureus (MRSA) populations. Nucleic Acids Res 41:7472–7484 http://dx.doi.org/10.1093/nar/gkt535. [PubMed]
51. Stegger M, Lindsay JA, Moodley A, Skov R, Broens EM, Guardabassi L. 2011. Rapid PCR detection of Staphylococcus aureus clonal complex 398 by targeting the restriction-modification system carrying sau1-hsdS1. J Clin Microbiol 49:732–734 http://dx.doi.org/10.1128/JCM.01970-10. [PubMed]
52. Diep BA, Gill SR, Chang RF, Phan TH, Chen JH, Davidson MG, Lin F, Lin J, Carleton HA, Mongodin EF, Sensabaugh GF, Perdreau-Remington F. 2006. Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus. Lancet 367:731–739 http://dx.doi.org/10.1016/S0140-6736(06)68231-7.
53. McCarthy AJ, Witney AA, Lindsay JA. 2012. Staphylococcus aureus temperate bacteriophage: carriage and horizontal gene transfer is lineage associated. Front Cell Infect Microbiol 2:6 http://dx.doi.org/10.3389/fcimb.2012.00006. [PubMed]
54. Lindsay JA, Ruzin A, Ross HF, Kurepina N, Novick RP. 1998. The gene for toxic shock toxin is carried by a family of mobile pathogenicity islands in Staphylococcus aureus. Mol Microbiol 29:527–543 http://dx.doi.org/10.1046/j.1365-2958.1998.00947.x. [PubMed]
55. Martínez-Rubio R, Quiles-Puchalt N, Martí M, Humphrey S, Ram G, Smyth D, Chen J, Novick RP, Penadés JR. 2017. Phage-inducible islands in the Gram-positive cocci. ISME J 11:1029–1042 http://dx.doi.org/10.1038/ismej.2016.163. [PubMed]
56. McCarthy AJ, Lindsay JA. 2012. The distribution of plasmids that carry virulence and resistance genes in Staphylococcus aureus is lineage associated. BMC Microbiol 12:104 http://dx.doi.org/10.1186/1471-2180-12-104. [PubMed]
57. Ruzin A, Lindsay J, Novick RP. 2001. Molecular genetics of SaPI1: a mobile pathogenicity island in Staphylococcus aureus. Mol Microbiol 41:365–377 http://dx.doi.org/10.1046/j.1365-2958.2001.02488.x. [PubMed]
58. Ubeda C, Olivarez NP, Barry P, Wang H, Kong X, Matthews A, Tallent SM, Christie GE, Novick RP. 2009. Specificity of staphylococcal phage and SaPI DNA packaging as revealed by integrase and terminase mutations. Mol Microbiol 72:98–108 http://dx.doi.org/10.1111/j.1365-2958.2009.06634.x. [PubMed]
59. Hiramatsu K, Ito T, Tsubakishita S, Sasaki T, Takeuchi F, Morimoto Y, Katayama Y, Matsuo M, Kuwahara-Arai K, Hishinuma T, Baba T. 2013. Genomic basis for methicillin resistance in Staphylococcus aureus. Infect Chemother 45:117–136 http://dx.doi.org/10.3947/ic.2013.45.2.117. [PubMed]
60. Ito T, Katayama Y, Asada K, Mori N, Tsutsumimoto K, Tiensasitorn C, Hiramatsu K. 2001. 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 http://dx.doi.org/10.1128/AAC.45.5.1323-1336.2001. [PubMed]
61. Holden MTG, Hsu LY, Kurt K, Weinert LA, Mather AE, Harris SR, Strommenger B, Layer F, Witte W, de Lencastre H, Skov R, Westh H, Zemlicková H, Coombs G, Kearns AM, Hill RLR, Edgeworth J, Gould I, Gant V, Cooke J, Edwards GF, McAdam PR, Templeton KE, McCann A, Zhou Z, Castillo-Ramírez S, Feil EJ, Hudson LO, Enright MC, Balloux F, Aanensen DM, Spratt BG, Fitzgerald JR, Parkhill J, Achtman M, Bentley SD, Nübel U. 2013. A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant Staphylococcus aureus pandemic. Genome Res 23:653–664 http://dx.doi.org/10.1101/gr.147710.112. [PubMed]
62. McCarthy AJ, van Wamel W, Vandendriessche S, Larsen J, Denis O, Garcia-Graells C, Uhlemann AC, Lowy FD, Skov R, Lindsay JA. 2012. Staphylococcus aureus CC398 clade associated with human-to-human transmission. Appl Environ Microbiol 78:8845–8848 http://dx.doi.org/10.1128/AEM.02398-12. [PubMed]
63. Strauß L, Stegger M, Akpaka PE, Alabi A, Breurec S, Coombs G, Egyir B, Larsen AR, Laurent F, Monecke S, Peters G, Skov R, Strommenger B, Vandenesch F, Schaumburg F, Mellmann A. 2017. Origin, evolution, and global transmission of community-acquired Staphylococcus aureus ST8. Proc Natl Acad Sci USA 114:E10596–E10604 http://dx.doi.org/10.1073/pnas.1702472114. [PubMed]
64. Planet PJ, Diaz L, Kolokotronis SO, Narechania A, Reyes J, Xing G, Rincon S, Smith H, Panesso D, Ryan C, Smith DP, Guzman M, Zurita J, Sebra R, Deikus G, Nolan RL, Tenover FC, Weinstock GM, Robinson DA, Arias CA. 2015. Parallel epidemics of community-associated methicillin-resistant Staphylococcus aureus USA300 infection in North and South America. J Infect Dis 212:1874–1882 http://dx.doi.org/10.1093/infdis/jiv320. [PubMed]
65. Rasooly A, Novick RP. 1993. Replication-specific inactivation of the pT181 plasmid initiator protein. Science 262:1048–1050 http://dx.doi.org/10.1126/science.8235621. [PubMed]
66. Firth N, Apisiridej S, Berg T, O’Rourke BA, Curnock S, Dyke KGH, Skurray RA. 2000. Replication of staphylococcal multiresistance plasmids. J Bacteriol 182:2170–2178 http://dx.doi.org/10.1128/JB.182.8.2170-2178.2000. [PubMed]
67. Partridge SR, Kwong SM, Firth N, Jensen SO. 2018. Mobile genetic elements associated with antimicrobial resistance. Clin Microbiol Rev 31:e00088-17 http://dx.doi.org/10.1128/CMR.00088-17. [PubMed]
68. Furi L, Haigh R, Al Jabri ZJH, Morrissey I, Ou HY, León-Sampedro R, Martinez JL, Coque TM, Oggioni MR. 2016. Dissemination of novel antimicrobial resistance mechanisms through the insertion sequence mediated spread of metabolic genes. Front Microbiol 7:1008 http://dx.doi.org/10.3389/fmicb.2016.01008. [PubMed]
69. Ziebuhr W, Krimmer V, Rachid S, Lössner I, Götz F, Hacker J. 1999. A novel mechanism of phase variation of virulence in Staphylococcus epidermidis: evidence for control of the polysaccharide intercellular adhesin synthesis by alternating insertion and excision of the insertion sequence element IS256. Mol Microbiol 32:345–356 http://dx.doi.org/10.1046/j.1365-2958.1999.01353.x. [PubMed]
70. Lindsay JA. 2014. Staphylococcus aureus genomics and the impact of horizontal gene transfer. Int J Med Microbiol 304:103–109 http://dx.doi.org/10.1016/j.ijmm.2013.11.010. [PubMed]
71. Morikawa K, Takemura AJ, Inose Y, Tsai M, Nguyen Thi T, Ohta T, Msadek T. 2012. Expression of a cryptic secondary sigma factor gene unveils natural competence for DNA transformation in Staphylococcus aureus. PLoS Pathog 8:e1003003 http://dx.doi.org/10.1371/journal.ppat.1003003. [PubMed]
72. Chen J, Ram G, Penadés JR, Brown S, Novick RP. 2015. Pathogenicity island-directed transfer of unlinked chromosomal virulence genes. Mol Cell 57:138–149 http://dx.doi.org/10.1016/j.molcel.2014.11.011. [PubMed]
73. Quiles-Puchalt N, Carpena N, Alonso JC, Novick RP, Marina A, Penadés JR. 2014. Staphylococcal pathogenicity island DNA packaging system involving cos-site packaging and phage-encoded HNH endonucleases. Proc Natl Acad Sci USA 111:6016–6021 http://dx.doi.org/10.1073/pnas.1320538111. [PubMed]
74. Stanczak-Mrozek KI, Laing KG, Lindsay JA. 2017. Resistance gene transfer: induction of transducing phage by sub-inhibitory concentrations of antimicrobials is not correlated to induction of lytic phage. J Antimicrob Chemother 72:1624–1631 http://dx.doi.org/10.1093/jac/dkx056. [PubMed]
75. Novick RP, Edelman I, Lofdahl S. 1986. Small Staphylococcus aureus plasmids are transduced as linear multimers that are formed and resolved by replicative processes. J Mol Biol 192:209–220 http://dx.doi.org/10.1016/0022-2836(86)90360-8.
76. Mašlaňová I, Doškař J, Varga M, Kuntová L, Mužík J, Malúšková D, Růžičková V, Pantůček R. 2013. Bacteriophages of Staphylococcus aureus efficiently package various bacterial genes and mobile genetic elements including SCC mec with different frequencies. Environ Microbiol Rep 5:66–73 http://dx.doi.org/10.1111/j.1758-2229.2012.00378.x. [PubMed]
77. Bayles KW, Brunskill EW, Iandolo JJ, Hruska LL, Huang S, Pattee PA, Smiley BK, Yasbin RE. 1994. A genetic and molecular characterization of the recA gene from Staphylococcus aureus. Gene 147:13–20 http://dx.doi.org/10.1016/0378-1119(94)90033-7.
78. McCarthy AJ, Loeffler A, Witney AA, Gould KA, Lloyd DH, Lindsay JA. 2014. Extensive horizontal gene transfer during Staphylococcus aureus co-colonization in vivo.Genome Biol Evol 6:2697–2708 http://dx.doi.org/10.1093/gbe/evu214. [PubMed]
79. Stanczak-Mrozek KI, Manne A, Knight GM, Gould K, Witney AA, Lindsay JA. 2015. Within-host diversity of MRSA antimicrobial resistances. J Antimicrob Chemother 70:2191–2198 http://dx.doi.org/10.1093/jac/dkv119. [PubMed]
80. Jamrozy D, Coll F, Mather AE, Harris SR, Harrison EM, MacGowan A, Karas A, Elston T, Estée Török M, Parkhill J, Peacock SJ. 2017. Evolution of mobile genetic element composition in an epidemic methicillin-resistant Staphylococcus aureus: temporal changes correlated with frequent loss and gain events. BMC Genomics 18:684 http://dx.doi.org/10.1186/s12864-017-4065-z. [PubMed]
81. Marraffini LA, Sontheimer EJ. 2008. CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA. Science 322:1843–1845 http://dx.doi.org/10.1126/science.1165771. [PubMed]
82. Holt DC, Holden MTG, Tong SYC, Castillo-Ramirez S, Clarke L, Quail MA, Currie BJ, Parkhill J, Bentley SD, Feil EJ, Giffard PM. 2011. A very early-branching Staphylococcus aureus lineage lacking the carotenoid pigment staphyloxanthin. Genome Biol Evol 3:881–895 http://dx.doi.org/10.1093/gbe/evr078. [PubMed]
83. Makarova KS, Haft DH, Barrangou R, Brouns SJJ, Charpentier E, Horvath P, Moineau S, Mojica FJM, Wolf YI, Yakunin AF, van der Oost J, Koonin EV. 2011. Evolution and classification of the CRISPR-Cas systems. Nat Rev Microbiol 9:467–477 http://dx.doi.org/10.1038/nrmicro2577. [PubMed]
84. Winstel V, Sanchez-Carballo P, Holst O, Xia G, Peschel A. 2014. Biosynthesis of the unique wall teichoic acid of Staphylococcus aureus lineage ST395. MBio 5:e00869 http://dx.doi.org/10.1128/mBio.00869-14. [PubMed]
85. Novick RP, Hoppensteadt FC. 1978. On plasmid incompatibility. Plasmid 1:421–434 http://dx.doi.org/10.1016/0147-619X(78)90001-X.
86. Uhlemann A-C, Dordel J, Knox JR, Raven KE, Parkhill J, Holden MTG, Peacock SJ, Lowy FD. 2014. Molecular tracing of the emergence, diversification, and transmission of S. aureus sequence type 8 in a New York community. Proc Natl Acad Sci USA 111:6738–6743 http://dx.doi.org/10.1073/pnas.1401006111. [PubMed]
87. Li M, Du X, Villaruz AE, Diep BA, Wang D, Song Y, Tian Y, Hu J, Yu F, Lu Y, Otto M. 2012. MRSA epidemic linked to a quickly spreading colonization and virulence determinant. Nat Med 18:816–819 http://dx.doi.org/10.1038/nm.2692. [PubMed]
88. Young BC, Wu CH, Gordon NC, Cole K, Price JR, Liu E, Sheppard AE, Perera S, Charlesworth J, Golubchik T, Iqbal Z, Bowden R, Massey RC, Paul J, Crook DW, Peto TE, Walker AS, Llewelyn MJ, Wyllie DH, Wilson DJ. 2017. Severe infections emerge from commensal bacteria by adaptive evolution. eLife 6:e30637 http://dx.doi.org/10.7554/eLife.30637.
89. Altman DR, Sullivan MJ, Chacko KI, Balasubramanian D, Pak TR, Sause WE, Kumar K, Sebra R, Deikus G, Attie O, Rose H, Lewis M, Fulmer Y, Bashir A, Kasarskis A, Schadt EE, Richardson AR, Torres VJ, Shopsin B, van Bakel H. 2018. Genome plasticity of agr-defective Staphylococcus aureus during clinical infection. Infect Immun 86:e00331-18 http://dx.doi.org/10.1128/IAI.00331-18. [PubMed]
90. Mayville P, Ji G, Beavis R, Yang H, Goger M, Novick RP, Muir TW. 1999. Structure-activity analysis of synthetic autoinducing thiolactone peptides from Staphylococcus aureus responsible for virulence. Proc Natl Acad Sci USA 96:1218–1223 http://dx.doi.org/10.1073/pnas.96.4.1218. [PubMed]
91. Ram G, Ross HF, Novick RP, Rodriguez-Pagan I, Jiang D. 2018. Conversion of staphylococcal pathogenicity islands to CRISPR-carrying antibacterial agents that cure infections in mice. Nat Biotechnol 36:971–976 http://dx.doi.org/10.1038/nbt.4203. [PubMed]
92. Benoit JB, Frank DN, Bessesen MT. 2018. Genomic evolution of Staphylococcus aureus isolates colonizing the nares and progressing to bacteremia. PLoS One 13:e0195860 http://dx.doi.org/10.1371/journal.pone.0195860. [PubMed]
93. Mairpady Shambat S, Siemens N, Monk IR, Mohan DB, Mukundan S, Krishnan KC, Prabhakara S, Snäll J, Kearns A, Vandenesch F, Svensson M, Kotb M, Gopal B, Arakere G, Norrby-Teglund A. 2016. A point mutation in AgrC determines cytotoxic or colonizing properties associated with phenotypic variants of ST22 MRSA strains. Sci Rep 6:31360 http://dx.doi.org/10.1038/srep31360. [PubMed]
94. Lilje B, Rasmussen RV, Dahl A, Stegger M, Skov RL, Fowler VG, Ng KL, Kiil K, Larsen AR, Petersen A, Johansen HK, Schønheyder HC, Arpi M, Rosenvinge FS, Korup E, Høst U, Hassager C, Gill SUA, Hansen TF, Johannesen TB, Smit J, Søgaard P, Skytt Andersen P, Eske-Bruun N. 2017. Whole-genome sequencing of bloodstream Staphylococcus aureus isolates does not distinguish bacteraemia from endocarditis. Microb Genom 6:doi:10.1099/mgen.0.000138. http://dx.doi.org/10.1099/mgen.0.000138 [PubMed]
95. Laabei M, Uhlemann AC, Lowy FD, Austin ED, Yokoyama M, Ouadi K, Feil E, Thorpe HA, Williams B, Perkins M, Peacock SJ, Clarke SR, Dordel J, Holden M, Votintseva AA, Bowden R, Crook DW, Young BC, Wilson DJ, Recker M, Massey RC. 2015. Evolutionary trade-offs underlie the multi-faceted virulence of Staphylococcus aureus. PLoS Biol 13:e1002229 http://dx.doi.org/10.1371/journal.pbio.1002229. [PubMed]
96. Boyle-Vavra S, Li X, Alam MT, Read TD, Sieth J, Cywes-Bentley C, Dobbins G, David MZ, Kumar N, Eells SJ, Miller LG, Boxrud DJ, Chambers HF, Lynfield R, Lee JC, Daum RS. 2015. USA300 and USA500 clonal lineages of Staphylococcus aureus do not produce a capsular polysaccharide due to conserved mutations in the cap5 locus. MBio 6:e02585-14 http://dx.doi.org/10.1128/mBio.02585-14. [PubMed]
97. Dupont CD, Scully IL, Zimnisky RM, Monian B, Rossitto CP, O’Connell EB, Jansen KU, Anderson AS, Love JC. 2018. Two vaccines for Staphylococcus aureus induce a B-cell-mediated immune response. MSphere 3:e00217-18 http://dx.doi.org/10.1128/mSphere.00217-18. [PubMed]
98. Knight GM, Budd EL, Whitney L, Thornley A, Al-Ghusein H, Planche T, Lindsay JA. 2012. Shift in dominant hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) clones over time. J Antimicrob Chemother 67:2514–2522 http://dx.doi.org/10.1093/jac/dks245. [PubMed]
99. Pinho MG, de Lencastre H, Tomasz A. 2001. An acquired and a native penicillin-binding protein cooperate in building the cell wall of drug-resistant staphylococci. Proc Natl Acad Sci USA 98:10886–10891 http://dx.doi.org/10.1073/pnas.191260798. [PubMed]
100. Stefani S, Chung DR, Lindsay JA, Friedrich AW, Kearns AM, Westh H, Mackenzie FM. 2012. Meticillin-resistant Staphylococcus aureus (MRSA): global epidemiology and harmonisation of typing methods. Int J Antimicrob Agents 39:273–282 http://dx.doi.org/10.1016/j.ijantimicag.2011.09.030. [PubMed]
101. Holden MTG, Lindsay JA, Corton C, Quail MA, Cockfield JD, Pathak S, Batra R, Parkhill J, Bentley SD, Edgeworth JD. 2010. Genome sequence of a recently emerged, highly transmissible, multi-antibiotic- and antiseptic-resistant variant of methicillin-resistant Staphylococcus aureus, sequence type 239 (TW). J Bacteriol 192:888–892 http://dx.doi.org/10.1128/JB.01255-09. [PubMed]
102. Robinson DA, Enright MC. 2004. Evolution of Staphylococcus aureus by large chromosomal replacements. J Bacteriol 186:1060–1064 http://dx.doi.org/10.1128/JB.186.4.1060-1064.2004. [PubMed]
103. Harbarth S, Liassine N, Dharan S, Herrault P, Auckenthaler R, Pittet D. 2000. Risk factors for persistent carriage of methicillin-resistant Staphylococcus aureus. Clin Infect Dis 31:1380–1385 http://dx.doi.org/10.1086/317484. [PubMed]
104. Cheng VCC, Li IWS, Wu AKL, Tang BSF, Ng KHL, To KKW, Tse H, Que TL, Ho PL, Yuen KY. 2008. Effect of antibiotics on the bacterial load of meticillin-resistant Staphylococcus aureus colonisation in anterior nares. J Hosp Infect 70:27–34 http://dx.doi.org/10.1016/j.jhin.2008.05.019. [PubMed]
105. Muller A, Mauny F, Talon D, Donnan PT, Harbarth S, Bertrand X. 2006. Effect of individual- and group-level antibiotic exposure on MRSA isolation: a multilevel analysis. J Antimicrob Chemother 58:878–881 http://dx.doi.org/10.1093/jac/dkl343. [PubMed]
106. Kanwar A, Cadnum JL, Jencson AL, Donskey CJ. 2018. Impact of antibiotic treatment on the burden of nasal Staphylococcus aureus among hospitalized patients. Antimicrob Agents Chemother 62:e00609 http://dx.doi.org/10.1128/AAC.00609-18. [PubMed]
107. Löffler B, Hussain M, Grundmeier M, Brück M, Holzinger D, Varga G, Roth J, Kahl BC, Proctor RA, Peters G. 2010. Staphylococcus aureus Panton-Valentine leukocidin is a very potent cytotoxic factor for human neutrophils. PLoS Pathog 6:e1000715 http://dx.doi.org/10.1371/journal.ppat.1000715. [PubMed]
108. Chen CJ, Unger C, Hoffmann W, Lindsay JA, Huang YC, Götz F. 2013. Characterization and comparison of 2 distinct epidemic community-associated methicillin-resistant Staphylococcus aureus clones of ST59 lineage. PLoS One 8:e63210 http://dx.doi.org/10.1371/journal.pone.0063210. [PubMed]
109. Strommenger B, Bartels MD, Kurt K, Layer F, Rohde SM, Boye K, Westh H, Witte W, De Lencastre H, Nübel U. 2014. Evolution of methicillin-resistant Staphylococcus aureus towards increasing resistance. J Antimicrob Chemother 69:616–622 http://dx.doi.org/10.1093/jac/dkt413. [PubMed]
110. Wassenberg MW, Bootsma MC, Troelstra A, Kluytmans JA, Bonten MJ. 2011. Transmissibility of livestock-associated methicillin-resistant Staphylococcus aureus (ST398) in Dutch hospitals. Clin Microbiol Infect 17:316–319 http://dx.doi.org/10.1111/j.1469-0691.2010.03260.x. [PubMed]
111. van Cleef BAGL, Graveland H, Haenen APJ, van de Giessen AW, Heederik D, Wagenaar JA, Kluytmans JAJW. 2011. Persistence of livestock-associated methicillin-resistant Staphylococcus aureus in field workers after short-term occupational exposure to pigs and veal calves. J Clin Microbiol 49:1030–1033 http://dx.doi.org/10.1128/JCM.00493-10. [PubMed]
112. Bens CCPM, Voss A, Klaassen CHW. 2006. Presence of a novel DNA methylation enzyme in methicillin-resistant Staphylococcus aureus isolates associated with pig farming leads to uninterpretable results in standard pulsed-field gel electrophoresis analysis. J Clin Microbiol 44:1875–1876 http://dx.doi.org/10.1128/JCM.44.5.1875-1876.2006. [PubMed]
113. McCarthy AJ, Witney AA, Gould KA, Moodley A, Guardabassi L, Voss A, Denis O, Broens EM, Hinds J, Lindsay JA. 2011. The distribution of mobile genetic elements (MGEs) in MRSA CC398 is associated with both host and country. Genome Biol Evol 3:1164–1174 http://dx.doi.org/10.1093/gbe/evr092. [PubMed]
114. Ye X, Wang X, Fan Y, Peng Y, Li L, Li S, Huang J, Yao Z, Chen S. 2016. Genotypic and phenotypic markers of livestock-associated methicillin-resistant Staphylococcus aureus CC9 in humans. Appl Environ Microbiol 82:3892–3899 http://dx.doi.org/10.1128/AEM.00091-16. [PubMed]
115. Chen CJ, Lauderdale TY, Lu CT, Chuang YY, Yang CC, Wu TS, Lee CY, Lu MC, Ko WC, Huang YC. 2018. Clinical and molecular features of MDR livestock-associated MRSA ST9 with staphylococcal cassette chromosome mecXII in humans. J Antimicrob Chemother 73:33–40 http://dx.doi.org/10.1093/jac/dkx357. [PubMed]
116. Larsen J, Stegger M, Andersen PS, Petersen A, Larsen AR, Westh H, Agersø Y, Fetsch A, Kraushaar B, Käsbohrer A, Feβler AT, Schwarz S, Cuny C, Witte W, Butaye P, Denis O, Haenni M, Madec JY, Jouy E, Laurent F, Battisti A, Franco A, Alba P, Mammina C, Pantosti A, Monaco M, Wagenaar JA, de Boer E, van Duijkeren E, Heck M, Domínguez L, Torres C, Zarazaga M, Price LB, Skov RL. 2016. Evidence for human adaptation and foodborne transmission of livestock-associated methicillin-resistant Staphylococcus aureus. Clin Infect Dis 63:1349–1352 http://dx.doi.org/10.1093/cid/ciw532. [PubMed]
117. Baines SL, Howden BP, Heffernan H, Stinear TP, Carter GP, Seemann T, Kwong JC, Ritchie SR, Williamson DA. 2016. Rapid emergence and evolution of Staphylococcus aureus clones harboring fusC-containing staphylococcal cassette chromosome elements. Antimicrob Agents Chemother 60:2359–2365 http://dx.doi.org/10.1128/AAC.03020-15.
118. Walters MS, Eggers P, Albrecht V, Travis T, Lonsway D, Hovan G, Taylor D, Rasheed K, Limbago B, Kallen A. 2015. Vancomycin-resistant Staphylococcus aureus: Delaware, 2015. MMWR Morb Mortal Wkly Rep 64:1056 http://dx.doi.org/10.15585/mmwr.mm6437a6. [PubMed]
119. Périchon B, Courvalin P. 2009. VanA-type vancomycin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 53:4580–4587 http://dx.doi.org/10.1128/AAC.00346-09. [PubMed]
120. Friães A, Resina C, Manuel V, Lito L, Ramirez M, Melo-Cristino J. 2015. Epidemiological survey of the first case of vancomycin-resistant Staphylococcus aureus infection in Europe. Epidemiol Infect 143:745–748 http://dx.doi.org/10.1017/S0950268814001423. [PubMed]
121. Rossi F, Diaz L, Wollam A, Panesso D, Zhou Y, Rincon S, Narechania A, Xing G, Di Gioia TSR, Doi A, Tran TT, Reyes J, Munita JM, Carvajal LP, Hernandez-Roldan A, Brandão D, van der Heijden IM, Murray BE, Planet PJ, Weinstock GM, Arias CA. 2014. Transferable vancomycin resistance in a community-associated MRSA lineage. N Engl J Med 370:1524–1531 http://dx.doi.org/10.1056/NEJMoa1303359. [PubMed]
122. Shekarabi M, Hajikhani B, Salimi Chirani A, Fazeli M, Goudarzi M. 2017. Molecular characterization of vancomycin-resistant Staphylococcus aureus strains isolated from clinical samples: a three year study in Tehran, Iran. PLoS One 12:e0183607 http://dx.doi.org/10.1371/journal.pone.0183607. [PubMed]
123. Icgen B. 2016. VanA-type MRSA (VRSA) emerged in surface waters. Bull Environ Contam Toxicol 97:359–366 http://dx.doi.org/10.1007/s00128-016-1827-2. [PubMed]
124. Saha B, Singh AK, Ghosh A, Bal M. 2008. Identification and characterization of a vancomycin-resistant Staphylococcus aureus isolated from Kolkata (South Asia). J Med Microbiol 57:72–79 http://dx.doi.org/10.1099/jmm.0.47144-0. [PubMed]
125. Howden BP, Peleg AY, Stinear TP. 2014. The evolution of vancomycin intermediate Staphylococcus aureus (VISA) and heterogenous-VISA. Infect Genet Evol 21:575–582 http://dx.doi.org/10.1016/j.meegid.2013.03.047. [PubMed]
126. Gardete S, Tomasz A. 2014. Mechanisms of vancomycin resistance in Staphylococcus aureus. J Clin Invest 124:2836–2840 http://dx.doi.org/10.1172/JCI68834. [PubMed]
127. van Wamel WJB, Rooijakkers SHM, Ruyken M, van Kessel KPM, van Strijp JAG. 2006. The innate immune modulators staphylococcal complement inhibitor and chemotaxis inhibitory protein of Staphylococcus aureus are located on β-hemolysin-converting bacteriophages. J Bacteriol 188:1310–1315 http://dx.doi.org/10.1128/JB.188.4.1310-1315.2006. [PubMed]
128. Rooijakkers SHM, Ruyken M, Roos A, Daha MR, Presanis JS, Sim RB, van Wamel WJB, van Kessel KPM, van Strijp JAG. 2005. Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases. Nat Immunol 6:920–927 http://dx.doi.org/10.1038/ni1235. [PubMed]
129. de Haas CJC, Veldkamp KE, Peschel A, Weerkamp F, Van Wamel WJB, Heezius ECJM, Poppelier MJJG, Van Kessel KPM, van Strijp JAG. 2004. Chemotaxis inhibitory protein of Staphylococcus aureus, a bacterial antiinflammatory agent. J Exp Med 199:687–695 http://dx.doi.org/10.1084/jem.20031636. [PubMed]
130. Peetermans M, Vanassche T, Liesenborghs L, Claes J, Vande Velde G, Kwiecinksi J, Jin T, De Geest B, Hoylaerts MF, Lijnen RH, Verhamme P. 2014. Plasminogen activation by staphylokinase enhances local spreading of S. aureus in skin infections. BMC Microbiol 14:310 http://dx.doi.org/10.1186/s12866-014-0310-7. [PubMed]
131. Vrieling M, Koymans KJ, Heesterbeek DAC, Aerts PC, Rutten VPMG, de Haas CJC, van Kessel KPM, Koets AP, Nijland R, van Strijp JAG. 2015. Bovine Staphylococcus aureus secretes the leukocidin LukMF′ to kill migrating neutrophils through CCR1. MBio 6:e00335 http://dx.doi.org/10.1128/mBio.00335-15. [PubMed]
132. Alonzo F III, Torres VJ. 2014. The bicomponent pore-forming leucocidins of Staphylococcus aureus. Microbiol Mol Biol Rev 78:199–230 http://dx.doi.org/10.1128/MMBR.00055-13. [PubMed]
133. Gillet Y, Issartel B, Vanhems P, Fournet JC, Lina G, Bes M, Vandenesch F, Piémont Y, Brousse N, Floret D, Etienne J. 2002. Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet 359:753–759 http://dx.doi.org/10.1016/S0140-6736(02)07877-7.
134. de Jong NWM, Vrieling M, Garcia BL, Koop G, Brettmann M, Aerts PC, Ruyken M, van Strijp JAG, Holmes M, Harrison EM, Geisbrecht BV, Rooijakkers SHM. 2018. Identification of a staphylococcal complement inhibitor with broad host specificity in equid Staphylococcus aureus strains. J Biol Chem 293:4468–4477 http://dx.doi.org/10.1074/jbc.RA117.000599.
135. Lowder BV, Guinane CM, Ben Zakour NL, Weinert LA, Conway-Morris A, Cartwright RA, Simpson AJ, Rambaut A, Nübel U, Fitzgerald JR. 2009. Recent human-to-poultry host jump, adaptation, and pandemic spread of Staphylococcus aureus. Proc Natl Acad Sci USA 106:19545–19550 http://dx.doi.org/10.1073/pnas.0909285106. [PubMed]
136. Mrochen DM, Grumann D, Schulz D, Gumz J, Trübe P, Pritchett-Corning K, Johnson S, Nicklas W, Kirsch P, Martelet K, Brandt JVD, Berg S, Bröker BM, Wiles S, Holtfreter S. 2018. Global spread of mouse-adapted Staphylococcus aureus lineages CC1, CC15, and CC88 among mouse breeding facilities. Int J Med Microbiol 308:598–606 http://dx.doi.org/10.1016/j.ijmm.2017.11.006. [PubMed]
137. Viana D, Comos M, McAdam PR, Ward MJ, Selva L, Guinane CM, González-Muñoz BM, Tristan A, Foster SJ, Fitzgerald JR, Penadés JR. 2015. A single natural nucleotide mutation alters bacterial pathogen host tropism. Nat Genet 47:361–366 http://dx.doi.org/10.1038/ng.3219. [PubMed]
138. Winstel V, Liang C, Sanchez-Carballo P, Steglich M, Munar M, Bröker BM, Penadés JR, Nübel U, Holst O, Dandekar T, Peschel A, Xia G. 2013. Wall teichoic acid structure governs horizontal gene transfer between major bacterial pathogens. Nat Commun 4:2345 http://dx.doi.org/10.1038/ncomms3345. [PubMed]
139. Krismer B, Weidenmaier C, Zipperer A, Peschel A. 2017. The commensal lifestyle of Staphylococcus aureus and its interactions with the nasal microbiota. Nat Rev Microbiol 15:675–687 http://dx.doi.org/10.1038/nrmicro.2017.104. [PubMed]
140. Kiser KB, Cantey-Kiser JM, Lee JC. 1999. Development and characterization of a Staphylococcus aureus nasal colonization model in mice. Infect Immun 67:5001–5006.
141. Syed AK, Ghosh S, Love NG, Boles BR. 2014. Triclosan promotes Staphylococcus aureus nasal colonization. MBio 5:e01015 http://dx.doi.org/10.1128/mBio.01015-13. [PubMed]
142. Krismer B, Liebeke M, Janek D, Nega M, Rautenberg M, Hornig G, Unger C, Weidenmaier C, Lalk M, Peschel A. 2014. Nutrient limitation governs Staphylococcus aureus metabolism and niche adaptation in the human nose. PLoS Pathog 10:e1003862 http://dx.doi.org/10.1371/journal.ppat.1003862. [PubMed]
143. Zipperer A, Konnerth MC, Laux C, Berscheid A, Janek D, Weidenmaier C, Burian M, Schilling NA, Slavetinsky C, Marschal M, Willmann M, Kalbacher H, Schittek B, Brötz-Oesterhelt H, Grond S, Peschel A, Krismer B. 2016. Human commensals producing a novel antibiotic impair pathogen colonization. Nature 539:314. [PubMed]
144. Scott JC, Sahl HG, Carne A, Tagg JR. 1992. Lantibiotic-mediated anti-lactobacillus activity of a vaginal Staphylococcus aureus isolate. FEMS Microbiol Lett 72:97–102 http://dx.doi.org/10.1111/j.1574-6968.1992.tb05047.x.
145. Nascimento JS, Ceotto H, Nascimento SB, Giambiagi-Demarval M, Santos KRN, Bastos MCF. 2006. Bacteriocins as alternative agents for control of multiresistant staphylococcal strains. Lett Appl Microbiol 42:215–221 http://dx.doi.org/10.1111/j.1472-765X.2005.01832.x. [PubMed]
146. Götz F, Perconti S, Popella P, Werner R, Schlag M. 2014. Epidermin and gallidermin: staphylococcal lantibiotics. Int J Med Microbiol 304:63–71 http://dx.doi.org/10.1016/j.ijmm.2013.08.012. [PubMed]
147. Severina E, Severin A, Tomasz A. 1998. Antibacterial efficacy of nisin against multidrug-resistant Gram-positive pathogens. J Antimicrob Chemother 41:341–347 http://dx.doi.org/10.1093/jac/41.3.341. [PubMed]
148. Uehara Y, Nakama H, Agematsu K, Uchida M, Kawakami Y, Abdul Fattah ASM, Maruchi N. 2000. Bacterial interference among nasal inhabitants: eradication of Staphylococcus aureus from nasal cavities by artificial implantation of Corynebacterium sp. J Hosp Infect 44:127–133 http://dx.doi.org/10.1053/jhin.1999.0680. [PubMed]
149. Bessesen MT, Kotter CV, Wagner BD, Adams JC, Kingery S, Benoit JB, Robertson CE, Janoff EN, Frank DN. 2015. MRSA colonization and the nasal microbiome in adults at high risk of colonization and infection. J Infect 71:649–657 http://dx.doi.org/10.1016/j.jinf.2015.08.008. [PubMed]
150. Margolis E, Yates A, Levin BR. 2010. The ecology of nasal colonization of Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus: the role of competition and interactions with host’s immune response. BMC Microbiol 10:59 http://dx.doi.org/10.1186/1471-2180-10-59. [PubMed]
151. O’Brien S, Fothergill JL. 2017. The role of multispecies social interactions in shaping Pseudomonas aeruginosa pathogenicity in the cystic fibrosis lung. FEMS Microbiol Lett 364:http://dx.doi.org/10.1093/femsle/fnx128. [PubMed]
152. Pernet E, Guillemot L, Burgel PR, Martin C, Lambeau G, Sermet-Gaudelus I, Sands D, Leduc D, Morand PC, Jeammet L, Chignard M, Wu Y, Touqui L. 2014. Pseudomonas aeruginosa eradicates Staphylococcus aureus by manipulating the host immunity. Nat Commun 5:5105 http://dx.doi.org/10.1038/ncomms6105. [PubMed]
153. Ford SA, Kao D, Williams D, King KC. 2016. Microbe-mediated host defence drives the evolution of reduced pathogen virulence. Nat Commun 7:13430 http://dx.doi.org/10.1038/ncomms13430. [PubMed]
154. King KC, Brockhurst MA, Vasieva O, Paterson S, Betts A, Ford SA, Frost CL, Horsburgh MJ, Haldenby S, Hurst GDD. 2016. Rapid evolution of microbe-mediated protection against pathogens in a worm host. ISME J 10:1915–1924 http://dx.doi.org/10.1038/ismej.2015.259. [PubMed]
155. Cooper LP, Roberts GA, White JH, Luyten YA, Bower EDM, Morgan RD, Roberts RJ, Lindsay JA, Dryden DTF. 2017. DNA target recognition domains in the Type I restriction and modification systems of Staphylococcus aureus. Nucleic Acids Res 45:3395–3406 https://doi.org/10.1093/nar/gkx067. [PubMed]
156. Bayliss SC, Hunt VL, Yokoyama M, Thorpe HA, Feil EJ. 2017. The use of Oxford Nanopore native barcoding for complete genome assembly. GigaScience 6:gix001, https://doi.org/10.1093/gigascience/gix001. [PubMed]
157. DeLeo FR, Kennedy AD, Chen L, Bubeck Wardenburg J, Kobayashi SD, Mathema B, Braughton KR, Whitney AR, Villaruz AE, Martens CA, Porcella SF, McGavin MJ, Otto M, Musser JM, Kreiswirth BN. 2011.Molecular differentiation of historic phage-type 80/81 and contemporary epidemic Staphylococcus aureus. PNAS 108:18091–18096 https://doi.org/10.1073/pnas.1111084108. [PubMed]

Article metrics loading...



Staphylococci, and in particular , cause an extensive variety of infections in a range of hosts. The comprehensive analysis of staphylococcal genomes reveals mechanisms controlling the organism’s biology, pathobiology, and dissemination. Whole-genome sequencing technologies led to a quantum leap in our understanding of bacterial genomes. The recent cost reduction of sequencing has resulted in unprecedented volumes of genomic information about , one of the most sequenced bacterial species. Collecting, comparing, and interpreting big data is challenging, but fascinating insights have emerged. For example, it is becoming clearer which selective pressures staphylococci face in their habitats and which mechanisms allow this pathogen to adapt, survive, and spread. A key theme is the constant evolution of staphylococci as they alter their genome, exchange DNA, and adapt to new environments, leading to the emergence of increasingly successful, antibiotic-resistant, immune-evading, and host-adapted colonizers and pathogens. This article introduces the structure of staphylococcal genomes, details how genomes vary between strains, outlines the mechanisms of genetic variation, and describes the features of successful clones.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Example of genomes illustrating variation in the core genome and mobile genetic elements. MRSA252, an example of a hospital-associated EMRSA16 ST36 CC30 isolate (left) and MSSA476, an example of a CC1 isolate (right). The core genome is highly conserved, with each lineage (CC) associated with specific variation. The outer gray ring indicates the location and distribution of the mobile genetic elements in these individual isolates, which can be highly variable. From reference 4 (https://www.pnas.org/content/101/26/9786/tab-figures-data).

Source: microbiolspec November 2019 vol. 7 no. 6 doi:10.1128/microbiolspec.GPP3-0071-2019
Permissions and Reprints Request Permissions
Download as Powerpoint

Supplemental Material

No supplementary material available for this content.

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