Genomic insights on heterogeneous resistance to vancomycin and teicoplanin in Methicillin-resistant Staphylococcus aureus: A first report from South India
Autoři:
Yamuna Devi Bakthavatchalam aff001; Priyanka Babu aff001; Elakkiya Munusamy aff001; Hariharan Triplicane Dwarakanathan aff002; Priscilla Rupali aff003; Marcus Zervos aff004; Peter John Victor aff005; Balaji Veeraraghavan aff001
Působiště autorů:
Department of Clinical Microbiology, Christian Medical College, Vellore, India
aff001; Department of Orthopaedics, Christian Medical College, Vellore, India
aff002; Infectious Diseases Training and Research Center (IDTRC), Christian Medical College, Vellore, India
aff003; Infectious Diseases, Henry Ford Health System, Detroit, Michigan, United States of America
aff004; Department of critical care unit, Christian Medical College, Vellore, India
aff005
Vyšlo v časopise:
PLoS ONE 14(12)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0227009
Souhrn
Methicillin-resistant Staphylococcus aureus (MRSA) infection is an important clinical concern in patients, and is often associated with significant disease burden and metastatic infections. There is an increasing evidence of heterogeneous vancomycin-intermediate S. aureus (hVISA) associated treatment failure. In this study, we aim to understand the molecular mechanism of teicoplanin resistant MRSA (TR-MRSA) and hVISA. A total of 482 MRSA isolates were investigated for these phenotypes. Of the tested isolates, 1% were identified as TR-MRSA, and 12% identified as hVISA. A highly diverse amino acid substitution was observed in tcaRAB, vraSR, and graSR genes in TR-MRSA and hVISA strains. Interestingly, 65% of hVISA strains had a D148Q mutation in the graR gene. However, none of the markers were reliable in differentiating hVISA from TR-MRSA. Significant pbp2 upregulation was noted in three TR-MRSA strains, which had teicoplanin MICs of 16 or 32 μg/ml, whilst significant pbp4 downregulation was not noted in these strains. In our study, multiple mutations were identified in the candidate genes, suggesting a complex evolutionary pathway involved in the development of TR-MRSA and hVISA strains.
Klíčová slova:
Staphylococcus aureus – Methicillin-resistant Staphylococcus aureus – Cell walls – Substitution mutation – Mutation detection – Vancomycin – Amino acid substitution – Autolysis
Zdroje
1. Melzer M, Eykyn SJ, Gransden WR, Chinn S. Is methicillin-resistant Staphylococcus aureus more virulent than methicillin-susceptible S. aureus? A comparative cohort study of British patients with nosocomial infection and bacteremia. Clin Infect Dis. 2003;37(11):1453–1460. doi: 10.1086/379321 14614667
2. Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing; 28th informational supplement. CLSI document M100-S28; 2018, Clinical and Laboratory Standards Institute, Wayne, PA.
3. European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters. 2018, version 8.0. http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_8.0_Breakpoint_Tables.pdf
4. Soriano A, Marco F, Martínez JA, Pisos E, Almela M, Dimova VP et al. Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis. 2008;46(2):193–200. doi: 10.1086/524667 18171250
5. Song KH, Kim M, Kim CJ, Cho JE, Choi YJ, Park JS et al. Impact of Vancomycin MIC on Treatment Outcomes in Invasive Staphylococcus aureus Infections. Antimicrob Agents Chemother. 2017;61(3). pii: e01845-16.
6. Chang HJ, Hsu PC, Yang CC, Siu LK, Kuo AJ, Chia JH, et al. Influence of teicoplanin MICs on treatment outcomes among patients with teicoplanin-treated methicillin-resistant Staphylococcus aureus bacteraemia: a hospital-based retrospective study. J Antimicrob Chemother. 2012;67(3):736–741. doi: 10.1093/jac/dkr531 22169187
7. Chen KY, Chang HJ, Hsu PC, Yang CC, Chia JH, Wu TL et al. Relationship of teicoplanin MICs to treatment failure in teicoplanin-treated patients with methicillin-resistant Staphylococcus aureus pneumonia. J Microbiol Immunol Infect. 2013;46(3):210–6. doi: 10.1016/j.jmii.2012.06.010 22999099
8. Howden BP, Davies JK, Johnson PD, Stinear TP, Grayson ML. Reduced vancomycin susceptibility in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications. Clin Microbiol Rev. 2010;23(1):99–139. doi: 10.1128/CMR.00042-09 20065327
9. Cepeda J, Hayman S, Whitehouse T, Kibbler CC, Livermore D, Singer M. Teicoplanin resistance in methicillin-resistant Staphylococcus aureus in an intensive care unit. J Antimicrob Chemother. 2003;52(3):533–4. doi: 10.1093/jac/dkg369 12888581
10. Gomes DM, Ward KE, LaPlante KL. Clinical implications of vancomycin heteroresistant and intermediately susceptible Staphylococcus aureus. Pharmacotherapy. 2015;35(4):424–432. doi: 10.1002/phar.1577 25884530
11. Zhang S, Sun X, Chang W, Dai Y, Ma X. Systematic Review and Meta-Analysis of the Epidemiology of Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Isolates. 2015;PLoS One.10(8):e0136082. doi: 10.1371/journal.pone.0136082 26287490
12. van Hal SJ, Jones M, Gosbell IB, Paterson DL. Vancomycin heteroresistance is associated with reduced mortality in ST239 methicillin-resistant Staphylococcus aureus blood stream infections. PLoS One. 2011;6(6):e21217. doi: 10.1371/journal.pone.0021217 21713004
13. Casapao AM, Leonard SN, Davis SL, Lodise TP, Patel N, Goff DA et al. Clinical Outcomes in Patients with Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Bloodstream Infection. Antimicrob Agents Chemother. 2013;57(9):4252–4259. doi: 10.1128/AAC.00380-13 23796929
14. Dhand A, Sakoulas G. Reduced vancomycin susceptibility among clinical Staphylococcus aureus isolates ('the MIC Creep'): implications for therapy. F1000 Med Rep. 2014;4:4.
15. Hiramatsu K. Vancomycin-resistant Staphylococcus aureus: a new model of antibiotic resistance. Lancet Infect Dis. 2001;1(3):147–155. doi: 10.1016/S1473-3099(01)00091-3 11871491
16. Clinical and Laboratory Standards Institute (CLSI). Methods for dilution of antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard, 9th ed. Document M07-A9. 2012; Clinical and Laboratory Standards Institute, Wayne, PA.
17. Deresinski S. The multiple paths to heteroresistance and intermediate resistance to vancomycin in Staphylococcus aureus. J Infect Dis. 2013;208(1):7–9. doi: 10.1093/infdis/jit136 23539742
18. Xu J, Pang L, Ma XX, Hu J, Tian Y, Yang YL et al. Phenotypic and Molecular Characterisation of Staphylococcus aureus with Reduced Vancomycin Susceptibility Derivated in Vitro. Open Med (Wars). 2018;13:475–486.
19. Cui L, Iwamoto A, Lian JQ, Neoh HM, Maruyama T, Horikawa Y, Hiramatsu K. Novel mechanism of antibiotic resistance originating in vancomycin-intermediate Staphylococcus aureus. Antimicrob Agents Chemother. 2006;50(2):428–38. doi: 10.1128/AAC.50.2.428-438.2006 16436693
20. Boyle-Vavra S, Yin S, Jo DS, Montgomery CP, Daum RS. VraT/YvqF is required for methicillin resistance and activation of the VraSR regulon in Staphylococcus aureus. Antimicrob Agents Chemother. 2013;57(1):83–95. doi: 10.1128/AAC.01651-12 23070169
21. Elsaghier AA, Aucken HM, Hamilton-Miller JM, Shaw S, Kibbler CC. Resistance to teicoplanin developing during treatment of methicillin-resistant Staphylococcus aureus infection. J Antimicrob Chemother. 2002;49(2):423–4. doi: 10.1093/jac/49.2.423 11815594
22. Szymanek-Majchrzak K, Mlynarczyk A, Mlynarczyk G. Characteristics of glycopeptide-resistant Staphylococcus aureus strains isolated from inpatients of three teaching hospitals in Warsaw, Poland. Antimicrob Resist Infect Control. 2018;7:105. doi: 10.1186/s13756-018-0397-y 30181870
23. Kato Y, Suzuki T, Ida T, Maebashi K. Genetic changes associated with glycopeptide resistance in Staphylococcus aureus: predominance of amino acid substitutions in YvqF/VraSR. J Antimicrob Chemother. 2010;65(1):37–45. doi: 10.1093/jac/dkp394 19889788
24. McCallum N, Berger-Bächi B, Senn MM. Regulation of antibiotic resistance in Staphylococcus aureus. Int J Med Microbiol. 2010;300(2–3):118–129. doi: 10.1016/j.ijmm.2009.08.015 19800843
25. Maki H, McCallum N, Bischoff M, Wada A, Berger-Bächi B. tcaA inactivation increases glycopeptide resistance in Staphylococcus aureus. Antimicrob Agents Chemother. 2004;48(6):1953–9. doi: 10.1128/AAC.48.6.1953-1959.2004 15155184
26. Brandenberger M, Tschierske M, Giachino P, Wada A, Berger-Bächi B. Inactivation of a novel three-cistronic operon tcaR-tcaA-tcaB increases teicoplanin resistance in Staphylococcus aureus. Biochim Biophys Acta. 2000;1523(2–3):135–9. doi: 10.1016/s0304-4165(00)00133-1 11042376
27. Wootton M, Macgowan AP, Walsh TR. Expression of tcaA and mprF and glycopeptide resistance in clinical glycopeptide-intermediate Staphylococcus aureus (GISA) and heteroGISA strains. Biochim Biophys Acta. 2005;1726(3):326–7. doi: 10.1016/j.bbagen.2005.09.002 16213099
28. Liu C, Chambers HF. Staphylococcus aureus with heterogeneous resistance to vancomycin: epidemiology, clinical significance, and critical assessment of diagnostic methods. Antimicrob Agents Chemother. 2003;47(10):3040–5. doi: 10.1128/AAC.47.10.3040-3045.2003 14506006
29. Brunet F, Vedel G, Dreyfus F, Vaxelaire JF, Giraud T, Schremmer B et al. Failure of teicoplanin therapy in two neutropenic patients with staphylococcal septicemia who recovered after administration of vancomycin. Eur J Clin Microbiol Infect Dis. 1990;9(2):145–7. doi: 10.1007/bf01963643 2138543
30. Hiramatsu K. Vancomycin-resistant Staphylococcus aureus: a new model of antibiotic resistance. Lancet Infect Dis. 2001;1(3):147–55. doi: 10.1016/S1473-3099(01)00091-3 11871491
31. Sieradzki K, Villari P, Tomasz A. Decreased susceptibilities to teicoplanin and vancomycin among coagulase-negative methicillin-resistant clinical isolates of staphylococci. Antimicrob Agents Chemother. 1998;42(1):100–7 9449268
32. Tille P. M., & Forbes B. A. Bailey & Scott's diagnostic microbiology (Thirteenth edition.). 2014;St. Louis, Missouri: Elsevier.
33. Khatib R, Riederer K, Sharma M, Shemes S, Iyer SP, Szpunar S. Screening for Intermediately Vancomycin-Susceptible and Vancomycin-Heteroresistant Staphylococcus aureus by Use of Vancomycin-Supplemented Brain Heart Infusion Agar Biplates: Defining Growth Interpretation Criteria Based on Gold Standard Confirmation. J Clin Microbiol. 2015;53(11):3543–6. doi: 10.1128/JCM.01620-15 26311860
34. Satola SW, Farley MM, Anderson KF, Patel JB. Comparison of detection methods for heteroresistant vancomycin-intermediate Staphylococcus aureus, with the population analysis profile method as the reference method. J Clin Microbiol. 2011;49(1):177–183. doi: 10.1128/JCM.01128-10 21048008
35. Wootton M, Howe RA, Hillman R, Walsh TR, Bennett PM, MacGowan AP. A modified population analysis profile (PAP) method to detect hetero-resistance to vancomycin in Staphylococcus aureus in a UK hospital. J Antimicrob Chemother. 2001;47(4):399–403. doi: 10.1093/jac/47.4.399 11266410
36. Rodriguez CA, Agudelo M, Zuluaga AF, Vesga O. Generic vancomycin enriches resistant subpopulations of Staphylococcus aureus after exposure in a neutropenic mouse thigh infection model. Antimicrob Agents Chemother. 2012;56(1):243–7. doi: 10.1128/AAC.05129-11 22064531
37. Chen CJ, Huang YC, Chiu CH. Multiple pathways of cross-resistance to glycopeptides and daptomycin in persistent MRSA bacteraemia. J Antimicrob Chemother. 2015;70(11):2965–72 doi: 10.1093/jac/dkv225 26216581
38. Goudarzi M, Seyedjavadi SS, Nasiri MJ, Goudarzi H, Sajadi Nia R, Dabiri H. Molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from patients with bacteremia based on MLST, SCCmec, spa, and agr locus types analysis. Microb Pathog. 2017;104:328–335. doi: 10.1016/j.micpath.2017.01.055 28159661
39. Zhang K, McClure JA, Elsayed S, Louie T, Conly JM. Novel multiplex PCR assay for characterization and concomitant subtyping of staphylococcal cassette chromosome mec types I to V in methicillin-resistant Staphylococcus aureus. J Clin Microbiol. 2005;43(10):5026–5033. doi: 10.1128/JCM.43.10.5026-5033.2005 16207957
40. Ghaznavi-Rad E, Nor Shamsudin M, Sekawi Z, van Belkum A, Neela V. A simplified multiplex PCR assay for fast and easy discrimination of globally distributed staphylococcal cassette chromosome mec types in meticillin-resistant Staphylococcus aureus. J Med Microbiol. 2010;59(Pt 10):1135–9. doi: 10.1099/jmm.0.021956-0 20616192
41. Harmsen D, Claus H, Witte W, Rothgänger J, Claus H, Turnwald D et al. Typing of methicillin-resistant Staphylococcus aureus in a university hospital setting by using novel software for spa repeat determination and database management. J Clin Microbiol. 2003;41(12):5442–8. doi: 10.1128/JCM.41.12.5442-5448.2003 14662923
42. Enright MC, Day NP, Davies CE, Peacock SJ, Spratt BG. Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus. J Clin Microbiol. 2000;38(3):1008–1015. 10698988
43. Ribeiro-Gonçalves B, Francisco AP, Vaz C, Ramirez M, Carriço JA. PHYLOViZ Online: web-based tool for visualization, phylogenetic inference, analysis and sharing of minimum spanning trees. Nucleic Acids Res. 2016;44(W1):W246–251. doi: 10.1093/nar/gkw359 27131357
44. Wattam A.R., Abraham D., Dalay O., Disz T.L., Driscoll T., Gabbard J.L., Gillespie J.J. et al. PATRIC, the bacterial bioinformatics database and analysis resource. Nucleic Acids Res. 2013;42:D581–591. doi: 10.1093/nar/gkt1099 24225323
45. Aziz RK, Bartels D, Best AA, DeJongh M, Disz T, Edwards RA et al. The RAST Server: rapid annotations using subsystems technology. BMC genomics. 2008;9(1):75
46. Overbeek R, Olson R, Pusch GD, Olsen GJ, Davis JJ, Disz T et al. The SEED and the Rapid Annotation of microbial genomes using Subsystems Technology (RAST). Nucleic acids research. 2013;42(D1):D206–214
47. Brettin T, Davis JJ, Disz T, Edwards RA, Gerdes S, Olsen GJ et al. RASTtk: a modular and extensible implementation of the RAST algorithm for building custom annotation pipelines and annotating batches of genomes. Scientific reports. 2015;5:8365 doi: 10.1038/srep08365 25666585
48. Ng PC, Henikoff S. Predicting deleterious amino acid substitutions. Genome Res. 2001;11(5):863–74. doi: 10.1101/gr.176601 11337480
49. Huang T, Wang P, Ye ZQ, Xu H, He Z, Feng KY et al. Prediction of deleterious non-synonymous SNPs based on protein interaction network and hybrid properties. PLoS One. 2010;5(7):e11900. doi: 10.1371/journal.pone.0011900 20689580
50. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D et al. Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks. Genome Research. 2003;13(11), 2498–2504. doi: 10.1101/gr.1239303 14597658
51. Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J et al. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Research. 2015; 43(Database issue), D447–52. doi: 10.1093/nar/gku1003 25352553
52. Renzoni A, Barras C, François P, Charbonnier Y, Huggler E, Garzoni C et al. Transcriptomic and functional analysis of an autolysis-deficient, teicoplanin-resistant derivative of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2006;50(9):3048–3061. doi: 10.1128/AAC.00113-06 16940101
53. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402–8. doi: 10.1006/meth.2001.1262 11846609
54. Vaudaux P, Francois P, Bisognano C, Kelley WL, Lew DP, Schrenzel J et al. Increased expression of clumping factor and fibronectin-binding proteins by hemB mutants of Staphylococcus aureus expressing small colony variant phenotypes. Infect Immun. 2002;70(10):5428–5437. doi: 10.1128/IAI.70.10.5428-5437.2002 12228267
55. Lodise TP, Graves J, Evans A, Graffunder E, Helmecke M, Lomaestro BM et al. Relationship between vancomycin MIC and failure among patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin. Antimicrob Agents Chemother. 2008;52(9):3315–3320. doi: 10.1128/AAC.00113-08 18591266
56. Sakoulas G, Moise-Broder PA, Schentag J, Forrest A, Moellering RC Jr, Eliopoulos GM. Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia. J Clin Microbiol. 2004;42(6):2398–2402. doi: 10.1128/JCM.42.6.2398-2402.2004 15184410
57. Yeh YC, Yeh KM, Lin TY, Chiu SK, Yang YS, Wang YC et al. Impact of vancomycin MIC creep on patients with methicillin-resistant Staphylococcus aureus bacteremia. J Microbiol Immunol Infect. 2012;45(3):214–220. doi: 10.1016/j.jmii.2011.11.006 22571999
58. Hiramatsu K, Kayayama Y, Matsuo M, Aiba Y, Saito M, Hishinuma T et al. Vancomycin-intermediate resistance in Staphylococcus aureus. J Glob Antimicrob Resist. 2014;2(4):213–224. doi: 10.1016/j.jgar.2014.04.006 27873679
59. Song JH, Hiramatsu K, Suh JY, Ko KS, Ito T, Kapi M et al. Asian Network for Surveillance of Resistant Pathogens Study Group. Emergence in Asian countries of Staphylococcus aureus with reduced susceptibility to vancomycin. Antimicrob Agents Chemother. 2004;48(12):4926–8. doi: 10.1128/AAC.48.12.4926-4928.2004 15561884
60. Chaudhari CN, Tandel K, Grover N, Sen S, Bhatt P, Sahni AK et al. Heterogeneous vancomycin-intermediate among methicillin resistant Staphylococcus aureus. Med J Armed Forces India. 2015;71(1):15–8. doi: 10.1016/j.mjafi.2014.03.008 25609857
61. Singh A, Prasad KN, Misra R, Rahman M, Singh SK, Rai RP et al. Increasing Trend of Heterogeneous Vancomycin Intermediate Staphylococcus aureus in a Tertiary Care Center of Northern India. Microb Drug Resist. 2015;21(5):545–50. doi: 10.1089/mdr.2015.0004 26430942
62. Wang Y, Li X, Jiang L, Han W, Xie X, Jin Y et al. Novel Mutation Sites in the Development of Vancomycin- Intermediate Resistance in Staphylococcus aureus. Front Microbiol. 2017;7:2163. doi: 10.3389/fmicb.2016.02163 28119680
63. Doddangoudar VC, Boost MV, Tsang DN, O'Donoghue MM. Tracking changes in the vraSR and graSR two component regulatory systems during the development and loss of vancomycin non-susceptibility in a clinical isolate. Clin Microbiol Infect. 2011;17(8):1268–1272. doi: 10.1111/j.1469-0691.2011.03463.x 21375655
64. Alam MT, Petit RA 3rd, Crispell EK, Thornton TA, Conneely KN, Jiang Y et al. Dissecting vancomycin-intermediate resistance in Staphylococcus aureus using genome-wide association. Genome Biol Evol. 2014;6(5):1174–1185. doi: 10.1093/gbe/evu092 24787619
65. Yoo JI, Kim JW, Kang GS, Kim HS, Yoo JS, Lee YS. Prevalence of amino acid changes in the yvqF, vraSR, graSR, and tcaRAB genes from vancomycin intermediate resistant Staphylococcus aureus. J Microbiol. 2013;51(2):160–5. doi: 10.1007/s12275-013-3088-7 23625215
66. Lin LC, Chang SC, Ge MC, Liu TP, Lu JJ. Novel single-nucleotide variations associated with vancomycin resistance in vancomycin-intermediate Staphylococcus aureus. Infect Drug Resist. 2018;11:113–123. doi: 10.2147/IDR.S148335 29403293
67. Hafer C, Lin Y, Kornblum J, Lowy FD, Uhlemann AC. Contribution of selected gene mutations to resistance in clinical isolates of vancomycin-intermediate Staphylococcus aureus. Antimicrob Agents Chemother. 2012;56(11):5845–5851. doi: 10.1128/AAC.01139-12 22948864
68. Watanabe Y, Cui L, Katayama Y, Kozue K, Hiramatsu K. Impact of rpoB mutations on reduced vancomycin susceptibility in Staphylococcus aureus. J Clin Microbiol. 2011;49(7):2680–4. doi: 10.1128/JCM.02144-10 21525224
69. Roch M, Clair P, Renzoni A, Reverdy ME, Dauwalder O, Bes M. Exposure of Staphylococcus aureus to subinhibitory concentrations of β-lactam antibiotics induces heterogeneous vancomycin-intermediate Staphylococcus aureus. Antimicrob Agents Chemother. 2014;58(9):5306–5314. doi: 10.1128/AAC.02574-14 24957836
70. Hu Q, Peng H, Rao X. Molecular Events for Promotion of Vancomycin Resistance in Vancomycin Intermediate Staphylococcus aureus. Front Microbiol. 2016;7:1601. doi: 10.3389/fmicb.2016.01601 27790199
71. Gao W, Cameron DR, Davies JK, Kostoulias X, Stepnell J, Tuck KL. The RpoB H₄₈₁Y rifampicin resistance mutation and an active stringent response reduce virulence and increase resistance to innate immune responses in Staphylococcus aureus. J Infect Dis. 2013;207(6):929–939. doi: 10.1093/infdis/jis772 23255563
72. Sieradzki K, Tomasz A. Alterations of cell wall structure and metabolism accompany reduced susceptibility to vancomycin in an isogenic series of clinical isolates of Staphylococcus aureus. J Bacteriol. 2003;185(24):7103–7110. doi: 10.1128/JB.185.24.7103-7110.2003 14645269
73. Gardete S, Tomasz A. Mechanisms of vancomycin resistance in Staphylococcus aureus. J Clin Invest. 2014;124(7):2836–2840 doi: 10.1172/JCI68834 24983424
74. Park C, Shin NY, Byun JH, Shin HH, Kwon EY, Choi SM. Downregulation of RNAIII in vancomycin-intermediate Staphylococcus aureus strains regardless of the presence of agr mutation. J Med Microbiol. 2012;61(Pt 3):345–352. doi: 10.1099/jmm.0.035204-0 22016559
75. Harigaya Y, Ngo D, Lesse AJ, Huang V, Tsuji BT. Characterization of heterogeneous vancomycin-intermediate resistance, MIC and accessory gene regulator (agr) dysfunction among clinical bloodstream isolates of Staphyloccocus aureus. BMC Infect Dis. 2011;11:287. doi: 10.1186/1471-2334-11-287 22026752
Článok vyšiel v časopise
PLOS One
2019 Číslo 12
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Nejasný stín na plicích – kazuistika
- Masturbační chování žen v ČR − dotazníková studie
- Těžké menstruační krvácení může značit poruchu krevní srážlivosti. Jaký management vyšetření a léčby je v takovém případě vhodný?
- Fixní kombinace paracetamol/kodein nabízí synergické analgetické účinky
Najčítanejšie v tomto čísle
- Methylsulfonylmethane increases osteogenesis and regulates the mineralization of the matrix by transglutaminase 2 in SHED cells
- Oregano powder reduces Streptococcus and increases SCFA concentration in a mixed bacterial culture assay
- The characteristic of patulous eustachian tube patients diagnosed by the JOS diagnostic criteria
- Parametric CAD modeling for open source scientific hardware: Comparing OpenSCAD and FreeCAD Python scripts