Effects of antibiotics on transformation and SOS response.
Abstract
Horizontal gene transfer plays important roles in the evolution of S. aureus, and indeed, a variety of virulence factors and antibiotic resistance genes are embedded in a series of mobile genetic elements. In this chapter, we review the mechanisms of horizontal gene transfer, including recent findings on the natural genetic competence. Then, we consider the transfer of two important antibiotic resistance genes: the methicillin resistance gene, mecA (in Staphylococcal Cassette Chromosome) and the linezolid resistance gene, cfr (in plasmid). In either case, distinct mechanisms driving the gene dissemination support the prominent evolutionary ability of this important human pathogen.
Keywords
- Transduction
- Conjugation
- Transformation
- staphylococcal cassette chromosome (SCC)
- cfr
1. Introduction
2. Horizontal gene transfer mechanisms
2.1. Phage‐related mechanisms
Phage‐mediated horizontal gene transfer is the major driving force for
In 1970s, a transformation‐like phenomenon (now termed “pseudo‐competence” or “pseudo‐transformation”) was described [13]. A series of studies have confirmed that it is a HGT mechanism that requires the presence of a staphylococcal phage [14]. The “competence‐conferring factor” was most likely the phage tail that has lytic activity. In some old bacteriology books, pseudo‐competence is regarded as competence, but the first report on genuine natural genetic competence was published on 2012 [15]. Pseudo‐competence was demonstrated to be distinct from natural competence: the important competence genes encoded in the
2.2. Conjugation
Bacterial conjugation has been studied in Gram‐negative and Gram‐positive species. Although broad‐host‐range plasmids able to replicate in both groups exist, the differences in terms of membrane and peptidoglycan cell wall require different conjugation systems on the basis of cell‐to‐cell recognition and contact.
Most of the conjugative staphylococcal plasmids studied belong to the incQ family. One of the better known staphylococcal conjugative plasmid is pGO1 [16], considered as the prototype of this type of plasmids. All the conjugative genes are located on a 14.5 kb region, and the minimal machinery necessary for conjugation includes the
Staphylococcal plasmids related to the pGO1/pSK41 family share an important homology regarding the organization of conjugative genes and, in addition, present an identical IncQ‐type relaxase and a nickase gene (
2.3. Natural transformation
Natural transformation requires the uptake of environmental DNA by the action of a set of DNA‐uptake proteins that are expressed in the bacterial membrane. Once DNA is incorporated into the cytoplasm, it can be used as a source of nutrients, as a template to repair damaged genetic material or to enhance bacterial fitness by generating diversity or introducing novel traits [21].
To undergo transformation, bacteria need to develop a specific physiological state called genetic competence. Competence is achieved through the regulated expression of the genes encoding the DNA uptake machinery [22]. In general, Gram‐positive DNA uptake machinery is formed by a pseudopilus (ComG proteins) that brings extracellular DNA to the cytoplasmic transport machinery, a DNA‐binding protein (the receptor ComEA) and a channel (ComEC). Only a single strand enters the cytosol, while the complementary strand is degraded by an endonuclease [23].
The regulation of competence development is a species‐specific process. In
Competence development is a species‐specific process that requires particular environmental conditions. These conditions include nutrient access, starvation, altered growth conditions and cell density [22]. Natural transformation in
Even in SigH‐expressing cells, the transformation frequencies change depending on the growth conditions, suggesting that there are additional levels of regulations for an efficient transformation. Importantly, antimicrobial agents also affect the transformation efficiencies in the SigH‐expressing cells [27]. Table 1 summarizes the effect of the antibiotics in
S. p* | L. p* | H. p* | ||||||
---|---|---|---|---|---|---|---|---|
TF** | SOS | TF** | SOS | TF** | TF** | TF** | ||
Fosfomycin | + [27] | |||||||
Vancomycin | +[27] | No effect [28] | ||||||
Oxacillin | - [27] | Yes [34, 35] | ||||||
Cefazolin | - [27] | |||||||
Ampicillin | Yes [36] | No effect [28] | No effect [29] | No effect [30] | ||||
Quinolones | Ciprofloxacin | No effect [27] | Yes [32] [37] | + [30] | ||||
Norfloxacin | - [31] | Yes [31] | + [28] | + [29] | ||||
Mitomycin C | - [27] | Yes [37] [38] | - [31] | Yes [31] | + [28] |
3. Dissemination of antibiotic resistance determinants
Since Fleming's discovery of penicillin and its application to treatment,
Type | Antibiotic | Gene | Location | Origin | Reported/probable HGT mechanism | Refs. |
---|---|---|---|---|---|---|
β‐lactams | Penicillin | Plasmid (transposon) | Conjugation Pseudo‐transformation | [40–42] | ||
Methicillin | Chromosome (SCC | CoNS | Transduction Conjugation Transformation | [15, 43–49] | ||
Glycopeptides | Vancomycin | Plasmid (transposon) | Conjugation | [50, 51] | ||
Aminoglycosides | Gentamicin Kanamycin Tobramycin | Plasmid (transposon) | Conjugation Transduction | [52] | ||
Antifolates | Trimethoprim | Plasmid (transposon) | Conjugation | [53, 54] | ||
Chromosome (IS) | – | [55] | ||||
Plasmid Chromosome (transposon) | ? | Conjugation - | [56–58] | |||
Macrolide Lincosamide Streptogramin B | Plasmid (transposon) | Streptococci | Conjugation Transduction | [59–61] | ||
Plasmid | CoNS | Transduction | [60, 62] | |||
Chromosome (transposon) | CoNS | Conjugation | [60, 62, 63] | |||
Tetracyclines | Tetracycline | Plasmid | Streptococci Enterococci | Conjugation | [64, 65] | |
Chromosome (transposon) | Streptococci | Conjugation | [61, 64] | |||
Chloramphenicol | Chloramphenicol | Plasmid | Conjugation Transduction | [8, 66, 67] | ||
Oxazolidinones | Lynezolid | Plasmid | CoNS? | Conjugation Transduction | [6] | |
Streptogramins | Dalfopristin | Plasmid | ? | Conjugation | [68, 69] | |
Fusidanes | Fusidic acid | Chromosome(SaPI) Plasmid | CoNS | Transduction | [11, 70] | |
Chromosome(SCC) | CoNS | – | [7–75] | |||
Phosphonic acids | Fosfomycin | Chromosome(SaPI) | ? | Transduction | [11] |
3.1. Dissemination of SCC
β‐lactams were the first line of antibiotics against
The
MRSA strains appeared in the hospital environment and spread rapidly causing serious clinical problems and several hospital outbreaks. The first MRSA strain was identified in the United Kingdom in 1961, and it carried the type I SCC
The origin of the SCC
The transfer mechanism of SCC
3.2. Dissemination of cfr
The
The
Up to 2007, the only known mechanism for linezolid resistance known in staphylococci was the spontaneous mutations in ribosomal proteins [92]. This non‐transmissible mechanism was associated with the previous intensive use of linezolid. The association of a potential transmissible mechanism of resistance to this antibiotic represented a global concern due to the scarce alternatives for the infections caused by these pathogens and also, due to the potential spreading of this resistance mechanism to the pathogenic bacterial pool.
When the first
In 2008, the first outbreak of linezolid‐resistant MRSA strain was reported in Spain [93]. The outbreak took place in the intensive care unit (ICU) of a public hospital and lasted 3 months. A total of 15 patients infected or colonized with linezolid‐resistant MRSA were detected. In this case, some isolates showed identical PFGE profiles, showing the clonal dissemination of the same linezolid‐resistant strain, but other
In 2008, the presence of plasmid‐borne
In 2010, during the analysis of a collection of Panton‐Valentine leukocidin (PVL)‐positive MRSA isolates from Ireland, one
Linezolid susceptibility among clinically significant isolates is monitored by different surveillance programs, such as Zyvox Annual Appraisal of Potency and Spectrum (ZAAPS) and the USA Linezolid Experience and Accurate Determination of Resistance (LEADER). According to the results obtained by these programs, linezolid resistance was 0.05% for
The impact of the transmission of
The second
While the observed situation suggested the spread of pSCFS7 among the staphylococci in Spain, in the USA, the situation regarding the prevalence of
Although conjugation alone was the recognized transmission mechanism for the
4. Conclusion
The prominent evolutionary ability of
Acknowledgments
We thank Ms. Nguyen Thi Le Thuy for her help. We acknowledge the supports from Pfizer Academic Contributions and Takeda Science Foundation.
References
- 1.
Lowy, F.D., Antimicrobial resistance: the example of Staphylococcus aureus. J Clin Invest, 2003. 111 (9): p. 1265–73. - 2.
Ito, T., et al., Insights on antibiotic resistance of Staphylococcus aureus from its whole genome: genomic island SCC. Drug Resist Updat, 2003. 6 (1): p. 41–52. - 3.
Chambers, H.F. and F.R. Deleo, Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat Rev Microbiol, 2009. 7 (9): p. 629–41. - 4.
Mongodin, E., et al., Microarray transcription analysis of clinical Staphylococcus aureus isolates resistant to vancomycin. J Bacteriol, 2003. 185 (15): p. 4638–4643. - 5.
Gu, B., et al., The emerging problem of linezolid‐resistant Staphylococcus. J Antimicrob Chemother, 2013. 68 (1): p. 4–11. - 6.
Cafini, F., et al., Horizontal gene transmission of the cfr gene to MRSA and Enterococcus: role of Staphylococcus epidermidis as a reservoir and alternative pathway for the spread of linezolid resistance. J Antimicrob Chemother, 2016. 71 (3): p. 587–92. - 7.
Lindsay, J.A., Genomic variation and evolution of Staphylococcus aureus. Int J Med Microbiol, 2010. 300 (2–3): p. 98–103. - 8.
Malachowa, N. and F.R. DeLeo, Mobile genetic elements of Staphylococcus aureus. Cell Mol Life Sci, 2010. 67 (18): p. 3057–71. - 9.
Deghorain, M. and L. Van Melderen, The Staphylococci phages family: an overview. Viruses, 2012. 4 (12): p. 3316–35. - 10.
McNamara, P.J., Genetic manipulation of Staphylococcus aureus, in Staphylococcus molecular genetics, J.A. Lindsay, Editor. 2008, Caister Academic Press: Norfolk, UK. p. 89–130. - 11.
Novick, R.P., G.E. Christie, and J.R. Penades, The phage‐related chromosomal islands of Gram‐positive bacteria. Nat Rev Microbiol, 2010. 8 (8): p. 541–51. - 12.
Uchiyama, J., et al., Intragenus generalized transduction in Staphylococcus spp. by a novel giant phage. ISME J, 2014. 8 (9): p. 1949–52. - 13.
Pattee, P.A. and D.S. Neveln, Transformation analysis of three linkage groups in Staphylococcus aureus. J Bacteriol, 1975. 124 (1): p. 201–11. - 14.
Birmingham, V.A. and P.A. Pattee, Genetic transformation in Staphylococcus aureus: isolation and characterization of a competence‐conferring factor from bacteriophage 80 alpha lysates. J Bacteriol, 1981. 148 (1): p. 301–7. - 15.
Morikawa, K., et al., Expression of a cryptic secondary sigma factor gene unveils natural competence for DNA transformation in Staphylococcus aureus. PLoS Pathog, 2012. 8 (11): p. e1003003. - 16.
Thomas, W.D., Jr. and G.L. Archer, Identification and cloning of the conjugative transfer region of Staphylococcus aureus plasmid pGO1. J Bacteriol, 1989. 171 (2): p. 684–91. - 17.
Berg, T., et al., Complete nucleotide sequence of pSK41: evolution of staphylococcal conjugative multiresistance plasmids. J Bacteriol, 1998. 180 (17): p. 4350–9. - 18.
Dougherty, B.A., et al., Sequence and analysis of the 60 kb conjugative, bacteriocin‐producing plasmid pMRC01 from Lactococcus lactis DPC3147. Mol Microbiol, 1998. 29 (4): p. 1029–38. - 19.
Schwarz, F.V., V. Perreten, and M. Teuber, Sequence of the 50‐kb conjugative multiresistance plasmid pRE25 from Enterococcus faecalis RE25. Plasmid, 2001. 46 (3): p. 170–87. - 20.
Ramsay, J.P., S.M. Kwong, Murphy, R.J.T., Eto, K.Y., Price, K.J., Nguyen, Q.T., O’Brien, F.G., Grubb, W.B., Coombs, G.W. Neville Firth An updated view of plasmid conjugation and mobilization in Staphylococcus. Mob Genet Elements, 2016. 6 (4): p. 1–11. - 21.
Chen, I., The ins and outs of DNA transfer in bacteria. Science, 2005. 310 (5753): p. 1456–60. - 22.
Thomas, C.M. and K.M. Nielsen, Mechanisms of, and barriers to, horizontal gene transfer between bacteria. Nat Rev Microbiol, 2005. 3 (9): p. 711–21. - 23.
Chen, I. and D. Dubnau, DNA uptake during bacterial transformation. Nat Rev Microbiol, 2004. 2 (3): p. 241–9. - 24.
Lindsay, J.A., Staphylococcus aureus genomics and the impact of horizontal gene transfer. Int J Med Microbiol, 2014. 304 (2): p. 103–9. - 25.
Morikawa, K., et al., A new staphylococcal sigma factor in the conserved gene cassette: functional significance and implication for the evolutionary processes. Genes Cells, 2003. 8 (8): p. 699–712. - 26.
Fagerlund, A., P.E. Granum, and L.S. Havarstein, Staphylococcus aureus competence genes: mapping of the SigH, ComK1 and ComK2 regulons by transcriptome sequencing. Mol Microbiol, 2014. 94 (3): p. 557–79. - 27.
Thi, Le T.N., V.M. Romero, and K. Morikawa, Cell wall‐affecting antibiotics modulate natural transformation in SigH‐expressing Staphylococcus aureus. J Antibiot (Tokyo), 2016. 69 (6): p. 464–6. - 28.
Prudhomme, M., et al., Antibiotic stress induces genetic transformability in the human pathogen Streptococcus pneumoniae. Science (New York, N.Y.), 2006. 313 (5783): p. 89–92. - 29.
Charpentier, X., et al., Antibiotics and UV radiation induce competence for natural transformation in Legionella pneumophila. J Bacteriol, 2011. 193 (5): p. 1114–21. - 30.
Dorer, M.S., J. Fero, and N.R. Salama, DNA damage triggers genetic exchange in Helicobacter pylori. PLoS Pathog, 2010. 6 (7): p. e1001026. - 31.
Boutry, C., et al., SOS response activation and competence development are antagonistic mechanisms in Streptococcus thermophilus. J Bacteriol, 2013. 195 (4): p. 696–707. - 32.
Cirz, R.T., et al., Complete and SOS‐mediated response of Staphylococcus aureus to the antibiotic ciprofloxacin. J Bacteriol, 2007. 189 (2): p. 531–9. - 33.
Ambur, O.H., et al., Genome dynamics in major bacterial pathogens. FEMS Microbiol Rev, 2009. 33 (3): p. 453–70. - 34.
Plata, K.B., et al., Targeting of PBP1 by beta‐lactams determines recA/SOS response activation in heterogeneous MRSA clinical strains. PLoS One, 2013. 8 (4): p. e61083. - 35.
Cuirolo, A., K. Plata, and A.E. Rosato, 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, 2009. 64 (1): p. 37–45. - 36.
Maiques, E., et al., beta‐lactam antibiotics induce the SOS response and horizontal transfer of virulence factors in Staphylococcus aureus. J Bacteriol, 2006. 188 (7): p. 2726–9. - 37.
Mesak, L.R., V. Miao, and J. Davies, Effects of subinhibitory concentrations of antibiotics on SOS and DNA repair gene expression in Staphylococcus aureus. Antimicrob Agents Chemother, 2008. 52 (9): p. 3394–7. - 38.
Anderson, K.L., et al., Characterization of the Staphylococcus aureus heat shock, cold shock, stringent, and SOS responses and their effects on log‐phase mRNA turnover. J Bacteriol, 2006. 188 (19): p. 6739–56. - 39.
Kali, A., Antibiotics and bioactive natural products in treatment of methicillin resistant Staphylococcus aureus: a brief review. Pharmacogn Rev, 2015. 9 (17): p. 29–34. - 40.
Anthonisen, I.L., et al., Organization of the antiseptic resistance gene qacA and Tn552‐related β‐lactamase genes in multidrug‐resistant Staphylococcus haemolyticus strains of animal and human origins. Antimicrob Agents Chemother, 2002. 46 (11): p. 3606–3612. - 41.
Novick, R.P., Genetic systems in staphylococci. Methods Enzymol, 1991. 204 : p. 587–636. - 42.
Lindberg, M., Sjostrom, J., Johansson, T., Transformation of chromosomal and plasmid characters in Staphylococcus aureus. J Bacteriol, 1972. 109 (2): p. 844–847. - 43.
Tsukubakishita, S., Kuwahara‐Arai, K., Baba, T., Hiramatsu, K., Staphylococcal cassette chromosome mec‐like element in Macrococcus caseolyticus. Antimicrob Agents Chemother, 2010. 54 (4): p. 1469–75. - 44.
Tsukubakishita, S., Kuwahara‐Arai, K., Sasaki, T., Hiramatsu, K., Origin and molecular evolution of the determinant of methicillin resistance in staphylococci. Antimicrob Agents Chemother, 2010. 54 (10): p. 4352–9. - 45.
Wu, S., Piscitelli, C., de Lencastre, H., Tomasz, A., Tracking the evolutionary origin of the methicillin resistance gene: cloning and sequencing of a homologue of mecA from a methicillin susceptible strain of Staphylococcus sciuri. Microb Drug Resist, 1996. 2 : p. 435–41. - 46.
Otto, M., Coagulase‐negative staphylococci as reservoirs of genes facilitating MRSA infection. Bioassays, 2013. 35 (1): p. 4–11. - 47.
Scharn, C., Tenover, F.C., Goering, R.V., Transduction of staphylococcal cassette chromosome mec elements between strains of Staphylococcus aureus. Antimicrob Agents Chemother, 2013. 57 (11): p. 5233–8. - 48.
Chlebowicz, M., Maslanova, I., Kuntova, L., Grundmann, H., Pantucek, R., Doskar, J., van Dijl, J.M, The Staphylococcal Cassette Chromosome mec type V from Staphylococcus aureus ST398 is packaged into bacteriophage capsids. Int J Med Microbiol, 2014. 304 (5–6): p. 764–74. - 49.
Ray, M., Boundy, S., Archer, G.L., Transfer of the methicillin resistance genomic island among staphylococci by conjugation. Mol Microbiol, 2016. 100 (4): p. 675–85. - 50.
Noble, W.C., Virani, Z., Cree R.G.A., Co‐transfer of vancomycin and other resistance genes from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus. FEMS Microbiol Lett, 1992. 93 : p. 195–8. - 51.
Sievert, D.M., M.L. Boulton, G. Stolman, D. Johnson, M.G. Stobierski, F.P. Downes, P.A. Somsel, J.T. Rudrik, W. Brown, W. Hafeez, T. Lundstrom, E. Flanagan, R. Johnson, J. Mitchel, S. Chang, Staphylococcus aureus resistant to vancomycin. MMWR Morb Mortal Wkly Rep, 2002. 51 : p. 565–7. - 52.
Rouch, D.A., Byrne, M.E., Kong, Y.C., Skurray, R.A., The aacA‐aphD gentamicin and kanamycin resistance determinant of TN4001 from Staphylococcus aureus: expression and nucleotide sequence analysis. J Gen Microbiol, 1987. 133 : p. 3039–52. - 53.
Rouch, D.A., Messerotti, L.J., Loo, L.S.L., Jackson, C.A., Skurray, R.A., Trimethroprim resistance transposon Tn4003 from Staphylococcus aureus encodes genes for a dihydrofolate reductase and thymidylate synthetase flanked by three copies of IS257. Mol Microbiol, 1989. 3 (2): p. 161–75. - 54.
Archer, G.L., Coughter, J.P., Johnston J.L, Plasmid‐encoded trimethoprim resistance in Staphylococci. Antimicrob Agents Chemother, 1986. 29 (5): p. 733–40. - 55.
Sekiguchi, J., et al., Cloning and characterization of a novel trimethoprim‐resistant dihydrofolate reductase from a nosocomial isolate of Staphylococcus aureus CM.S2 (IMCJ1454). Antimicrob Agents Chemother, 2005. 49 (9): p. 3948–51. - 56.
Kadlec, K. and S. Schwarz, Identification of a novel trimethoprim resistance gene, dfrK, in a methicillin‐resistant Staphylococcus aureus ST398 strain and its physical linkage to the tetracycline resistance gene tet(L). Antimicrob Agents Chemother, 2009. 53 (2): p. 776–8. - 57.
Kadlec, K., et al., Unusual small plasmids carrying the novel resistance genes dfrK or apmA isolated from methicillin‐resistant or ‐susceptible staphylococci. J Antimicrob Chemother, 2012. 67 (10): p. 2342–5. - 58.
Schwarz, S., et al., Plasmid‐mediated antimicrobial resistance in staphylococci and other firmicutes. Microbiol Spectr, 2014. 2 (6):PLAS-0020-2014.doi:10.1128/microbiolspec.PLAS-0020-2014 - 59.
Khan, S.A., Novick R., Terminal nucleotide sequences of Tn551, a transposon specifying erythromycin resistance in Staphylococcus aureus: homology with Tn3. Plasmid, 1980. 4 : p. 148–54. - 60.
Leclercq, R., Courvalin, P., Bacterial resistance to macrolide, lincosamide, and streptogramin antibiotics by target modification. Antimicrob Agents Chemother, 1991. 35 (7): p. 1267–72. - 61.
Trieu-Cuot P, Poyart-Salmeron C, Carlier C, Courvalin P. Molecular dissection of the transposition mechanism of conjugative transposons from Gram-positive cocci. In: Dunny G M, Patrick P, Cleary L L, editors. Genetics and molecular biology of streptococci, lactococci, and enterococci. Washington, D.C: American Society for Microbiology; 1991. pp. 21–27. - 62.
Thakker‐Varia, S., Jenssen, W.D., Moon‐Mcdermott, L., Weinstein, M.P., Dubin, D.T., Molecular epidemiology of Macrolides‐Lincosamides‐Streptogramin B resistance in Staphylococcus aureus and Coagulase‐Negative Staphylococci. Antimicrob Agents Chemother, 1987. 31 (5): p. 735–43. - 63.
Murphy, E., Nucleotide Sequence of ermA, a macrolide‐lincosamide‐streptogramin B determinant in Staphylococcus aureus. J Bacteriol, 1985. 162 (2): p. 633–40. - 64.
Chopra, I. and M. Roberts, Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev, 2001. 65 (2): p. 232–60. - 65.
Bismuth, R., Zilhao, R., Sakamoto, H., Guesdon, J., Courvalin, P, Gene heterogeneity for tetracycline resistance in Staphylococcus spp. Antimicrob Agents Chemother, 1990. 34 (8): p. 1611–14. - 66.
Lyon, B.R., Skurray, R., Antimicrobial resistance of Staphylococcus aureus: genetic basis. Microbiol Rev, 1987. 51 (1): p. 88–134. - 67.
Tennent, J.M., May, J.W., Skurray, R.A., Characterisation of chloramphenicol resistance plasmids of Staphylococcus aureus and S. epidermidis by restriction enzyme mapping techniques. J Med Microbiol, 1986. 22 : p. 79–84. - 68.
Hershberger, E., Donabedian, S., Konstantinou, K., Zervos, M.J., Quinupristin‐Dalfopristin resistance in Gram‐Positive bacteria: mechanism of resistance and epidemiology. Clin Infect Dis, 2004. 38 (92–98). - 69.
Allignet, J., El Solh, N., Comparative analysis of staphylococcal plasmids carrying three streptogramin‐resistance genes: vat‐vgb‐vga. Plasmid, 1999. 42 : p. 134–138. - 70.
Yazdankhah, S.P., et al., Fusidic acid resistance, mediated by fusB, in bovine coagulase‐negative staphylococci. J Antimicrob Chemother, 2006. 58 (6): p. 1254–1256. - 71.
Hung, W.C., et al., Skin commensal staphylococci may act as reservoir for fusidic acid resistance genes. PLoS One, 2015. 10 (11): p. e0143106. - 72.
Lin, Y.T., et al., A novel staphylococcal cassette chromosomal element, SCCfusC, carrying fusC and speG in fusidic acid‐resistant methicillin‐resistant Staphylococcus aureus. Antimicrob Agents Chemother, 2014. 58 (2): p. 1224–7. - 73.
Holden, M.T., et al., Complete genomes of two clinical Staphylococcus aureus strains: evidence for the rapid evolution of virulence and drug resistance. Proc Natl Acad Sci U S A, 2004. 101 (26): p. 9786–91. - 74.
Ender, M., B. Berger‐Bachi, and N. McCallum, Variability in SCCmecN1 spreading among injection drug users in Zurich, Switzerland. BMC Microbiol, 2007. 7 : p. 62. - 75.
Kinnevey, P.M., 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): p. 524–31. - 76.
Jevons, M., ”Celbenin”‐resistant staphylococci. Br Med J, 1961. 124 : p. 124–5. - 77.
Peacock, S., Paterson, GK., Mechanisms of methicillin resistance in Staphylococcus aureus. Annu Rev Biochem, 2015. 84 : p. 577–601. - 78.
Ito, T., Y. Katayama, and K. Hiramatsu, Cloning and nucleotide sequence determination of the entire mec DNA of pre‐methicillin‐resistant Staphylococcus aureus N315. Antimicrob Agents Chemother, 1999. 43 (6): p. 1449–58. - 79.
Katayama, Y., T. Ito, and K. Hiramatsu, A new class of genetic element, staphylococcus cassette chromosome mec, encodes methicillin resistance in Staphylococcus aureus. Antimicrob Agents Chemother, 2000. 44 (6): p. 1549–55. - 80.
(IWG‐SCC), I.W.G.o.t.C.o.S.C.C.E., Classification of staphylococcal cassette chromosome mec (SCCmec): guidelines for reporting novel SCCmec elements. Antimicrob Agents Chemother, 2009. 53 (12): p. 4961–7. - 81.
Kloos, W.E., Ballard, D.N., George, C.G., Webster, J.A., Hubner, R.J., Ludwig, W., Schleifer, K.H. Fiedler, F. and Schubert, K., Delimiting the genus Staphylococcus through description of Macrococcus caseolyticus gen. nov., comb. nov. and Macrococcus equipercicus sp. nov., and Macrococcus bovicus sp. nov. and Macrococcus carouselicus sp. nov. J Syst Bacteriol, 1998. 48 : p. 859–77. - 82.
Ito, T., Katayama, Y., Asada, K., Mori, N., Tsutsumimoto, K., Tiensasitorn, C., Hiramatsu, K., 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): p. 1323–36. - 83.
Ito, T., Ma, XX., Takekuchi, 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): p. 2637–51. - 84.
Ma, X., Ito, T., Tiensasitorn, C., Jamklnag, M., Chongtrakool, P., Boyle‐Vavra, S., Daum, R.S., Hiramatsu, K., Novel type of staphylococcal cassette chromosome mec identified in community‐acquired methicillin‐resistant Staphylococcus aureus strains. Antimicrob Agents Chemother, 2002. 46 (4): p. 1147–52. - 85.
Barbier, F., Ruppe, E., Hernandez, D., Lebaux, D., Methicillin‐resistant coagulase‐negative staphylococci in the community: high homology of SCCmec IVa between Staphylococcus epidermidis and major clones of methicillin‐resistant Staphylococcus aureus. J Infect Dis, 2010. 202 : p. 270–281. - 86.
Bouchami, O., Ben Hassen, A., Lencastre, H., Miragaia, M., Molecular epidemiology of methicillin‐resistant Staphylococcus hominis (MRSHo): low clonality and reservoirs of SCCmec structural elements. PLoS One, 2011. 6 (7): p. e21940. - 87.
Bouchami, O., Ben Hassen, A., Lencastre, H., Miragaia, M., High prevalence of mec complex C and ccrC is independent of SCCmec type V in Staphylococcus haemolyticus. Eur J Clin Microbiol Infect Dis, 2011. 31 (4): p. 605–14. - 88.
Schwarz, S., C. Werckenthin, and C. Kehrenberg, Identification of a plasmid‐borne chloramphenicol‐florfenicol resistance gene in Staphylococcus sciuri. Antimicrob Agents Chemother, 2000. 44 (9): p. 2530–3. - 89.
Murphy, E., L. Huwyler, and C. de Freire Bastos Mdo, Transposon Tn554: complete nucleotide sequence and isolation of transposition‐defective and antibiotic‐sensitive mutants. EMBO J, 1985. 4 (12): p. 3357–65. - 90.
Toh, S.M., et al., Acquisition of a natural resistance gene renders a clinical strain of methicillin‐resistant Staphylococcus aureus resistant to the synthetic antibiotic linezolid. Mol Microbiol, 2007. 64 (6): p. 1506–14. - 91.
Livermore, D.M., Linezolid in vitro: mechanism and antibacterial spectrum. J Antimicrob Chemother, 2003. 51 (Suppl 2): p. ii9–16. - 92.
Locke, J.B., M. Hilgers, and K.J. Shaw, Mutations in ribosomal protein L3 are associated with oxazolidinone resistance in staphylococci of clinical origin. Antimicrob Agents Chemother, 2009. 53 (12): p. 5275–8. - 93.
Sanchez Garcia, M., et al., Clinical outbreak of linezolid‐resistant Staphylococcus aureus in an intensive care unit. JAMA, 2010. 303 (22): p. 2260–4. - 94.
Mendes, R.E., et al., First report of cfr‐mediated resistance to linezolid in human staphylococcal clinical isolates recovered in the United States. Antimicrob Agents Chemother, 2008. 52 (6): p. 2244–6. - 95.
Kehrenberg, C. and S. Schwarz, Distribution of florfenicol resistance genes fexA and cfr among chloramphenicol‐resistant Staphylococcus isolates. Antimicrob Agents Chemother, 2006. 50 (4): p. 1156–63. - 96.
Wang, Y., et al., Detection of the staphylococcal multiresistance gene cfr in Proteus vulgaris of food animal origin. J Antimicrob Chemother, 2011. 66 (11): p. 2521–6. - 97.
Wang, Y., et al., Detection of the staphylococcal multiresistance gene cfr in Macrococcus caseolyticus and Jeotgalicoccus pinnipedialis. J Antimicrob Chemother, 2012. 67 (8): p. 1824–7. - 98.
Liu, Y., et al., Transferable multiresistance plasmids carrying cfr in Enterococcus spp. from swine and farm environment. Antimicrob Agents Chemother, 2013. 57 (1): p. 42–8. - 99.
Shore, A.C., 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, 2010. 54 (12): p. 4978–84. - 100.
Klevens, R.M., et al., Invasive methicillin‐resistant Staphylococcus aureus infections in the United States. JAMA, 2007. 298 (15): p. 1763–71. - 101.
Flamm, R.K., et al., An international activity and spectrum analysis of linezolid: ZAAPS Program results for 2011. Diagn Microbiol Infect Dis, 2013. 76 (2): p. 206–13. - 102.
Flamm, R.K., et al., Linezolid surveillance results for the United States: LEADER surveillance program 2011. Antimicrob Agents Chemother, 2013. 57 (2): p. 1077–81. - 103.
Baos, E., et al., Characterization and monitoring of linezolid‐resistant clinical isolates of Staphylococcus epidermidis in an intensive care unit 4 years after an outbreak of infection by cfr‐mediated linezolid‐resistant Staphylococcus aureus. Diagn Microbiol Infect Dis, 2013. 76 (3): p. 325–9. - 104.
Gopegui, E.R., et al., 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, 2012. 56 (4): p. 2139–42. - 105.
Lozano, C., et al., Characterization of a cfr‐positive methicillin‐resistant Staphylococcus epidermidis strain of the lineage ST22 implicated in a life‐threatening human infection. Diagn Microbiol Infect Dis, 2012. 73 (4): p. 380–2. - 106.
Fessler, A.T., et al., Cfr‐mediated linezolid resistance in methicillin‐resistant Staphylococcus aureus and Staphylococcus haemolyticus associated with clinical infections in humans: two case reports. J Antimicrob Chemother, 2014. 69 (1): p. 268–70. - 107.
Mendes, R.E., et al., Dissemination of a pSCFS3‐like cfr‐carrying plasmid in Staphylococcus aureus and Staphylococcus epidermidis clinical isolates recovered from hospitals in Ohio. Antimicrob Agents Chemother, 2013. 57 (7): p. 2923–8. - 108.
Bender, J., et al., Linezolid resistance in clinical isolates of Staphylococcus epidermidis from German hospitals and characterization of two cfr‐carrying plasmids. J Antimicrob Chemother, 2015. 70 (6): p. 1630–8.