1887

Abstract

A key characteristic of infections, and one that also varies phenotypically between clones, is that of biofilm formation, which aids in bacterial persistence through increased adherence and immune evasion. Though there is a general understanding of the process of biofilm formation – adhesion, proliferation, maturation and dispersal – the tightly orchestrated molecular events behind each stage, and what drives variation between strains, has yet to be unravelled. Herein we measure biofilm progression and dispersal in real-time across the five major CDC-types (USA100-USA500) revealing adherence patterns that differ markedly amongst strains. To gain insight into this, we performed transcriptomic profiling on these isolates at multiple timepoints, compared to planktonically growing counterparts. Our findings support a model in which eDNA release, followed by increased positive surface charge, perhaps drives initial abiotic attachment. This is seemingly followed by cooperative repression of autolysis and activation of poly-N-acetylglucosamine (PNAG) production, which may indicate a developmental shift in structuring the biofilm matrix. As biofilms mature, diminished translational capacity was apparent, with 53 % of all ribosomal proteins downregulated, followed by upregulation of anaerobic respiration enzymes. These findings are noteworthy because reduced cellular activity and an altered metabolic state have been previously shown to contribute to higher antibiotic tolerance and bacterial persistence. In sum, this work is, to our knowledge, the first study to investigate transcriptional regulation during the early, establishing phase of biofilm formation, and to compare global transcriptional regulation both temporally and across multiple clonal lineages.

Funding
This study was supported by the:
  • National Institute of Allergy and Infectious Diseases (Award AI124458)
    • Principle Award Recipient: LindseyN Shaw
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000598
2021-07-06
2021-08-04
Loading full text...

Full text loading...

/deliver/fulltext/mgen/7/7/mgen000598.html?itemId=/content/journal/mgen/10.1099/mgen.0.000598&mimeType=html&fmt=ahah

References

  1. Centers for Disease Control and Prevention (CDC) Antibiotic resistance threats in the United States, 2019. In U.S. Department of Health and Human Services c Atlanta, GA: Antibiotic Resistance Coordination and Strategy Unit; 2019
    [Google Scholar]
  2. Otto M. Staphylococcus colonization of the skin and antimicrobial peptides. Expert Rev Dermatol 2010; 5:183–195 [View Article] [PubMed]
    [Google Scholar]
  3. Nouwen JL, Fieren MW, Snijders S, Verbrugh HA, van Belkum A. Persistent (not intermittent) nasal carriage of Staphylococcus aureus is the determinant of CPD-related infections. Kidney Int 2005; 67:1084–1092 [View Article] [PubMed]
    [Google Scholar]
  4. Donlan RM. Biofilms and device-associated infections. Emerg Infect Dis 2001; 7:277–281 [View Article] [PubMed]
    [Google Scholar]
  5. Trampuz A, Piper KE, Jacobson MJ, Hanssen AD, Unni KK et al. Sonication of removed hip and knee prostheses for diagnosis of infection. N Engl J Med 2007; 357:654–663 [View Article] [PubMed]
    [Google Scholar]
  6. Schilcher K, Horswill AR. Staphylococcal biofilm development: Structure, regulation, and treatment strategies. Microbiol Mol Biol Rev 2020; 84: [View Article] [PubMed]
    [Google Scholar]
  7. Stewart PS. Mechanisms of antibiotic resistance in bacterial biofilms. Int J Med Microbiol 2002; 292:107–113 [View Article] [PubMed]
    [Google Scholar]
  8. Bernard L, Hoffmeyer P, Assal M, Vaudaux P, Schrenzel J et al. Trends in the treatment of orthopaedic prosthetic infections. J Antimicrob Chemother 2004; 53:127–129 [View Article] [PubMed]
    [Google Scholar]
  9. Kunutsor SK, Beswick AD, Whitehouse MR, Wylde V, Blom AW. Debridement, antibiotics and implant retention for periprosthetic joint infections: A systematic review and meta-analysis of treatment outcomes. J Infect 2018; 77:479–488 [View Article] [PubMed]
    [Google Scholar]
  10. Herrmann M, Vaudaux PE, Pittet D, Auckenthaler R, Lew PD et al. Fibronectin, fibrinogen, and laminin act as mediators of adherence of clinical staphylococcal isolates to foreign material. J Infect Dis 1988; 158:693–701 [View Article] [PubMed]
    [Google Scholar]
  11. Franz S, Rammelt S, Scharnweber D, Simon JC. Immune responses to implants - a review of the implications for the design of immunomodulatory biomaterials. Biomaterials 2011; 32:6692–6709 [View Article] [PubMed]
    [Google Scholar]
  12. Moormeier DE, Bayles KW. Staphylococcus aureus biofilm: a complex developmental organism. Mol Microbiol 2017; 104:365–376 [View Article] [PubMed]
    [Google Scholar]
  13. McDevitt D, Francois P, Vaudaux P, Foster TJ. Molecular characterization of the clumping factor (fibrinogen receptor) of Staphylococcus aureus. Mol Microbiol 1994; 11:237–248 [View Article] [PubMed]
    [Google Scholar]
  14. Barbu EM, Mackenzie C, Foster TJ, Hook M. SdrC induces staphylococcal biofilm formation through a homophilic interaction. Mol Microbiol 2014; 94:172–185 [View Article] [PubMed]
    [Google Scholar]
  15. Bose JL, Lehman MK, Fey PD, Bayles KW. Contribution of the staphylococcus aureus ATL AM and GL murein hydrolase activities in cell division, autolysis, and biofilm formation. PLoS One 2012; 7:e42244 [View Article] [PubMed]
    [Google Scholar]
  16. Herman-Bausier P, El-Kirat-Chatel S, Foster TJ, Geoghegan JA, Dufrêne YF. Staphylococcus aureus fibronectin-binding protein a mediates cell-cell adhesion through low-affinity homophilic bonds. mBio 2015; 6:e00413–15 [View Article] [PubMed]
    [Google Scholar]
  17. Merino N, Toledo-Arana A, Vergara-Irigaray M, Valle J, Solano C et al. Protein A-mediated multicellular behavior in Staphylococcus aureus. J Bacteriol 2009; 191:832–843 [View Article] [PubMed]
    [Google Scholar]
  18. Brady RA, Leid JG, Kofonow J, Costerton JW, Shirtliff ME. Immunoglobulins to surface-associated biofilm immunogens provide a novel means of visualization of methicillin-resistant Staphylococcus aureus biofilms. Appl Environ Microbiol 2007; 73:6612–6619 [View Article] [PubMed]
    [Google Scholar]
  19. Wang SH, Khan Y, Hines L, Mediavilla JR, Zhang L et al. Methicillin-resistant Staphylococcus aureus sequence type 239-III, Ohio, USA, 2007-2009. Emerg Infect Dis 2012; 18:1557–1565 [View Article] [PubMed]
    [Google Scholar]
  20. King JM, Kulhankova K, Stach CS, BG V, Salgado-Pabon W. Phenotypes and virulence among Staphylococcus aureus usa100, usa200, usa300, usa400, and usa600 clonal lineages. mSphere 2016; 1: [View Article]
    [Google Scholar]
  21. Fowler VG Jr, Nelson CL, McIntyre LM, Kreiswirth BN, Monk A et al. Potential associations between hematogenous complications and bacterial genotype in staphylococcus aureus infection. J Infect Dis 2007; 196:738–747 [View Article] [PubMed]
    [Google Scholar]
  22. McDougal LK, Steward CD, Killgore GE, Chaitram JM, McAllister SK et al. Pulsed-field gel electrophoresis typing of oxacillin-resistant Staphylococcus aureus isolates from the United States: establishing a national database. J Clin Microbiol 2003; 41:5113–5120 [View Article] [PubMed]
    [Google Scholar]
  23. Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K et al. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 2007; 298:1763–1771 [View Article] [PubMed]
    [Google Scholar]
  24. Diekema DJ, Richter SS, Heilmann KP, Dohrn CL, Riahi F et al. Continued emergence of USA300 methicillin-resistant Staphylococcus aureus in the United States: results from a nationwide surveillance study. Infect Control Hosp Epidemiol 2014; 35:285–292 [View Article] [PubMed]
    [Google Scholar]
  25. Tenover FC, Tickler IA, Goering RV, Kreiswirth BN, Mediavilla JR et al. Characterization of nasal and blood culture isolates of methicillin-resistant Staphylococcus aureus from patients in United States Hospitals. Antimicrob Agents Chemother 2012; 56:1324–1330 [View Article] [PubMed]
    [Google Scholar]
  26. Hageman JC, Uyeki TM, Francis JS, Jernigan DB, Wheeler JG et al. Severe community-acquired pneumonia due to Staphylococcus aureus, 2003-04 influenza season. Emerg Infect Dis 2006; 12:894–899 [View Article] [PubMed]
    [Google Scholar]
  27. Tenover FC, Goering RV. Methicillin-resistant Staphylococcus aureus strain USA300: origin and epidemiology. J Antimicrob Chemother 2009; 64:441–446 [View Article] [PubMed]
    [Google Scholar]
  28. Tong SYC, Davis JS, Eichenberger E, Holland TL, Fowler VG Jr. Staphylococcus aureus infections: Epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev 2015; 28:603–661 [View Article] [PubMed]
    [Google Scholar]
  29. Li M, Diep BA, Villaruz AE, Braughton KR, Jiang X et al. Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus. Proc Natl Acad Sci U S A 2009; 106:5883–5888 [View Article] [PubMed]
    [Google Scholar]
  30. Adem PV, Montgomery CP, Husain AN, Koogler TK, Arangelovich V et al. Staphylococcus aureus sepsis and the Waterhouse-Friderichsen syndrome in children. N Engl J Med 2005; 353:1245–1251 [View Article] [PubMed]
    [Google Scholar]
  31. Brosnahan AJ, Schlievert PM. Gram-positive bacterial superantigen outside-in signaling causes toxic shock syndrome. FEBS J 2011; 278:4649–4667 [View Article] [PubMed]
    [Google Scholar]
  32. Limbago B, Fosheim GE, Schoonover V, Crane CE, Nadle J et al. Characterization of methicillin-resistant Staphylococcus aureus isolates collected in 2005 and 2006 from patients with invasive disease: a population-based analysis. J Clin Microbiol 2009; 47:1344–1351 [View Article] [PubMed]
    [Google Scholar]
  33. Sabirova JS, Hernalsteens JP, De Backer S, Xavier BB, Moons P et al. Fatty acid kinase A is an important determinant of biofilm formation in Staphylococcus aureus USA300. BMC Genomics 2015; 16:861 [View Article] [PubMed]
    [Google Scholar]
  34. Vanhommerig E, Moons P, Pirici D, Lammens C, Hernalsteens J-P et al. Comparison of biofilm formation between major clonal lineages of methicillin resistant staphylococcus aureus. PLoS One 2014; 9:e104561 [View Article] [PubMed]
    [Google Scholar]
  35. Walker JN, Horswill AR. A coverslip-based technique for evaluating Staphylococcus aureus biofilm formation on human plasma. Front Cell Infect Microbiol 2012; 2:39 [View Article] [PubMed]
    [Google Scholar]
  36. Mishra B, Lushnikova T, Wang G. Small lipopeptides possess anti-biofilm capability comparable to daptomycin and vancomycin. RSC Adv 2015; 5:59758–59769 [View Article] [PubMed]
    [Google Scholar]
  37. McAdow M, Kim HK, Dedent AC, Hendrickx APA, Schneewind O et al. Preventing staphylococcus aureus sepsis through the inhibition of its agglutination in blood. PLoS Pathog 2011; 7:e1002307 [View Article] [PubMed]
    [Google Scholar]
  38. Peterson PK, Verhoef J, Sabath LD, Quie PG. Effect of protein A on staphylococcal opsonization. Infect Immun 1977; 15:760–764 [View Article] [PubMed]
    [Google Scholar]
  39. Archer NK, Mazaitis MJ, Costerton JW, Leid JG, Powers ME et al. Staphylococcus aureus biofilms: properties, regulation, and roles in human disease. Virulence 2011; 2:445–459 [View Article] [PubMed]
    [Google Scholar]
  40. Cassat JE, Lee CY, Smeltzer MS. Investigation of biofilm formation in clinical isolates of Staphylococcus aureus. Methods Mol Biol 2007; 391:127–144 [View Article] [PubMed]
    [Google Scholar]
  41. Carroll RK, Weiss A, Shaw LN. RNA-Sequencing of Staphylococcus aureus messenger RNA. Methods Mol Biol 2016; 1373:131–141 [View Article] [PubMed]
    [Google Scholar]
  42. Glaser P, Martins-Simões P, Villain A, Barbier M, Tristan A et al. Demography and intercontinental spread of the usa300 community-acquired methicillin-resistant staphylococcus aureus lineage. MBio 2016; 7:e02183–15 [View Article] [PubMed]
    [Google Scholar]
  43. Robinson MD, Oshlack A. A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol 2010; 11:R25 [View Article] [PubMed]
    [Google Scholar]
  44. Krzywinski M, Schein J, Birol I, Connors J, Gascoyne R et al. Circos: an information aesthetic for comparative genomics. Genome Res 2009; 19:1639–1645 [View Article] [PubMed]
    [Google Scholar]
  45. Moreno-Hagelsieb G, Latimer K. Choosing BLAST options for better detection of orthologs as reciprocal best hits. Bioinformatics 2008; 24:319–324 [View Article] [PubMed]
    [Google Scholar]
  46. Kanehisa M, Sato Y, Kawashima M, Furumichi M, Tanabe M. KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res 2016; 44:D457–62 [View Article] [PubMed]
    [Google Scholar]
  47. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 2008; 3:1101–1108 [View Article] [PubMed]
    [Google Scholar]
  48. Gutiérrez D, Hidalgo-Cantabrana C, Rodríguez A, García P, Ruas-Madiedo P. Monitoring in real time the formation and removal of biofilms from clinical related pathogens using an impedance-based technology. PLoS One 2016; 11:e0163966 [View Article] [PubMed]
    [Google Scholar]
  49. Atienza JM, Zhu J, Wang X, Xu X, Abassi Y. Dynamic monitoring of cell adhesion and spreading on microelectronic sensor arrays. J Biomol Screen 2005; 10:795–805 [View Article]
    [Google Scholar]
  50. Peeters E, Nelis HJ, Coenye T. Comparison of multiple methods for quantification of microbial biofilms grown in microtiter plates. J Microbiol Methods 2008; 72:157–165 [View Article] [PubMed]
    [Google Scholar]
  51. Moormeier DE, Bose JL, Horswill AR, Bayles KW. Temporal and stochastic control of Staphylococcus aureus biofilm development. mBio 2014; 5:e01341–14 [View Article] [PubMed]
    [Google Scholar]
  52. Beenken KE, Dunman PM, McAleese F, Macapagal D, Murphy E et al. Global gene expression in Staphylococcus aureus biofilms. J Bacteriol 2004; 186:4665–4684 [View Article] [PubMed]
    [Google Scholar]
  53. Resch A, Rosenstein R, Nerz C, Gotz F. Differential gene expression profiling of Staphylococcus aureus cultivated under biofilm and planktonic conditions. Appl Environ Microbiol 2005; 71:2663–2676 [View Article] [PubMed]
    [Google Scholar]
  54. Yao Y, Sturdevant DE, Otto M. Genomewide analysis of gene expression in Staphylococcus epidermidis biofilms: insights into the pathophysiology of S. epidermidis biofilms and the role of phenol-soluble modulins in formation of biofilms. J Infect Dis 2005; 191:289–298 [View Article] [PubMed]
    [Google Scholar]
  55. Cendra MDM, Blanco-Cabra N, Pedraz L, Torrents E. Optimal environmental and culture conditions allow the in vitro coexistence of Pseudomonas aeruginosa and Staphylococcus aureus in stable biofilms. Sci Rep 2019; 9:1628416284 [View Article] [PubMed]
    [Google Scholar]
  56. Rani SA, Pitts B, Beyenal H, Veluchamy RA, Lewandowski Z et al. Spatial patterns of DNA replication, protein synthesis, and oxygen concentration within bacterial biofilms reveal diverse physiological states. J Bacteriol 2007; 189:4223–4233 [View Article] [PubMed]
    [Google Scholar]
  57. Burne RA, Chen YY. Bacterial ureases in infectious diseases. Microbes Infect 2000; 2:533–542 [View Article] [PubMed]
    [Google Scholar]
  58. Leibig M, Liebeke M, Mader D, Lalk M, Peschel A et al. Pyruvate formate lyase acts as a formate supplier for metabolic processes during anaerobiosis in Staphylococcus aureus. J Bacteriol 2011; 193:952–962 [View Article] [PubMed]
    [Google Scholar]
  59. Frey M, Rothe M, Wagner AF, Knappe J. Adenosylmethionine-dependent synthesis of the glycyl radical in pyruvate formate-lyase by abstraction of the glycine C-2 pro-S hydrogen atom. Studies of [2H]glycine-substituted enzyme and peptides homologous to the glycine 734 site. Journal of Biological Chemistry 1994; 269:12432–12437 [View Article]
    [Google Scholar]
  60. Chastanet A, Fert J, Msadek T. Comparative genomics reveal novel heat shock regulatory mechanisms in Staphylococcus aureus and other Gram-positive bacteria. Mol Microbiol 2003; 47:1061 [View Article] [PubMed]
    [Google Scholar]
  61. Kruger E, Zuhlke D, Witt E, Ludwig H, Hecker M. Clp-mediated proteolysis in Gram-positive bacteria is autoregulated by the stability of a repressor. EMBO J 2001; 20:852–863 [View Article] [PubMed]
    [Google Scholar]
  62. Mogk A, Homuth G, Scholz C, Kim L, Schmid FX et al. The GroE chaperonin machine is a major modulator of the CIRCE heat shock regulon of Bacillus subtilis. EMBO J 1997; 16:4579–4590 [View Article] [PubMed]
    [Google Scholar]
  63. Engman J, Rogstam A, Frees D, Ingmer H, von Wachenfeldt C. The YjbH adaptor protein enhances proteolysis of the transcriptional regulator Spx in Staphylococcus aureus. J Bacteriol 2012; 194:1186–1194 [View Article] [PubMed]
    [Google Scholar]
  64. Maiques E, Ubeda C, Campoy S, Salvador N, Lasa I et al. beta-lactam antibiotics induce the SOS response and horizontal transfer of virulence factors in Staphylococcus aureus. J Bacteriol 2006; 188:2726–2729 [View Article] [PubMed]
    [Google Scholar]
  65. Luebke JL, Shen J, Bruce KE, Kehl-Fie TE, Peng H et al. The CsoR-like sulfurtransferase repressor (CstR) is a persulfide sensor in Staphylococcus aureus. Mol Microbiol 2014; 94:1343–1360 [View Article] [PubMed]
    [Google Scholar]
  66. Pamp SJ, Frees D, Engelmann S, Hecker M, Ingmer H. Spx is a global effector impacting stress tolerance and biofilm formation in Staphylococcus aureus. J Bacteriol 2006; 188:4861–4870 [View Article] [PubMed]
    [Google Scholar]
  67. Bisognano C, Kelley WL, Estoppey T, Francois P, Schrenzel J et al. A recA-LexA-dependent pathway mediates ciprofloxacin-induced fibronectin binding in Staphylococcus aureus. J Biol Chem 2004; 279:9064–9071 [View Article] [PubMed]
    [Google Scholar]
  68. Baker J, Sengupta M, Jayaswal RK, Morrissey JA. The Staphylococcus aureus CsoR regulates both chromosomal and plasmid-encoded copper resistance mechanisms. Environ Microbiol 2011; 13:2495–2507 [View Article] [PubMed]
    [Google Scholar]
  69. Frees D, Chastanet A, Qazi S, Sorensen K, Hill P et al. Clp ATPases are required for stress tolerance, intracellular replication and biofilm formation in Staphylococcus aureus. Mol Microbiol 2004; 54:1445–1462 [View Article]
    [Google Scholar]
  70. Mann EE, Rice KC, Boles BR, Endres JL, Ranjit D et al. Modulation of eDNA release and degradation affects staphylococcus aureus biofilm maturation. PLoS One 2009; 4:e5822 [View Article] [PubMed]
    [Google Scholar]
  71. Ranjit DK, Endres JL, Bayles KW. Staphylococcus aureus CidA and LrgA proteins exhibit holin-like properties. J Bacteriol 2011; 193:2468–2476 [View Article] [PubMed]
    [Google Scholar]
  72. Peschel A, Otto M, Jack RW, Kalbacher H, Jung G et al. Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to defensins, protegrins, and other antimicrobial peptides. J Biol Chem 1999; 274:8405–8410 [View Article] [PubMed]
    [Google Scholar]
  73. Peschel A, Jack RW, Otto M, Collins LV, Staubitz P et al. Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with l-lysine. J Exp Med 2001; 193:1067–1076 [View Article] [PubMed]
    [Google Scholar]
  74. Gross M, Cramton SE, Gotz F, Peschel A. Key role of teichoic acid net charge in Staphylococcus aureus colonization of artificial surfaces. Infect Immun 2001; 69:3423–3426 [View Article] [PubMed]
    [Google Scholar]
  75. Koprivnjak T, Mlakar V, Swanson L, Fournier B, Peschel A et al. Cation-induced transcriptional regulation of the dlt operon of Staphylococcus aureus. J Bacteriol 2006; 188:3622–3630 [View Article] [PubMed]
    [Google Scholar]
  76. Yang SJ, Bayer AS, Mishra NN, Meehl M, Ledala N et al. The Staphylococcus aureus two-component regulatory system, GraRS, senses and confers resistance to selected cationic antimicrobial peptides. Infect Immun 2012; 80:74–81 [View Article] [PubMed]
    [Google Scholar]
  77. Liang X, Zheng L, Landwehr C, Lunsford D, Holmes D et al. Global regulation of gene expression by ArlRS, a two-component signal transduction regulatory system of Staphylococcus aureus. J Bacteriol 2005; 187:5486–5492 [View Article] [PubMed]
    [Google Scholar]
  78. Fournier B, Hooper DC. A new two-component regulatory system involved in adhesion, autolysis, and extracellular proteolytic activity of Staphylococcus aureus. J Bacteriol 2000; 182:3955–3964 [View Article] [PubMed]
    [Google Scholar]
  79. Burgui S, Gil C, Solano C, Lasa I, Valle J. A systematic evaluation of the Two-Component systems network reveals that ArlRS is a key regulator of catheter colonization by Staphylococcus aureus. Front Microbiol 2018; 9:342 [View Article] [PubMed]
    [Google Scholar]
  80. Groicher KH, Firek BA, Fujimoto DF, Bayles KW. The Staphylococcus aureus lrgAB operon modulates murein hydrolase activity and penicillin tolerance. J Bacteriol 2000; 182:1794–1801 [View Article] [PubMed]
    [Google Scholar]
  81. Komatsuzawa H, Ohta K, Fujiwara T, Choi GH, Labischinski H et al. Cloning and sequencing of the gene, fmtC, which affects oxacillin resistance in methicillin-resistant Staphylococcus aureus. FEMS Microbiol Lett 2001; 203:49–54 [View Article] [PubMed]
    [Google Scholar]
  82. Mlynek KD, Callahan MT, Shimkevitch AV, Farmer JT, Endres JL et al. Effects of Low-Dose Amoxicillin on Staphylococcus aureus USA300 Biofilms. Antimicrob Agents Chemother 2016; 60:2639–2651 [View Article] [PubMed]
    [Google Scholar]
  83. Bai J, Zhu X, Zhao K, Yan Y, Xu T et al. The role of ArlRS in regulating oxacillin susceptibility in methicillin-resistant Staphylococcus aureus indicates it is a potential target for antimicrobial resistance breakers. Emerg Microbes Infect 2019; 8:503–515 [View Article] [PubMed]
    [Google Scholar]
  84. Meehl M, Herbert S, Gotz F, Cheung A. Interaction of the GraRS two-component system with the VraFG ABC transporter to support vancomycin-intermediate resistance in Staphylococcus aureus. . Antimicrob Agents Chemother 2007; 51:2679–2689 [View Article] [PubMed]
    [Google Scholar]
  85. Peschel A, Vuong C, Otto M, Gotz F. The D-alanine residues of Staphylococcus aureus teichoic acids alter the susceptibility to vancomycin and the activity of autolytic enzymes. Antimicrob Agents Chemother 2000; 44:2845–2847 [View Article] [PubMed]
    [Google Scholar]
  86. Rice KC, Firek BA, Nelson JB, Yang SJ, Patton TG et al. The Staphylococcus aureus cidAB operon: evaluation of its role in regulation of murein hydrolase activity and penicillin tolerance. J Bacteriol 2003; 185:2635–2643 [View Article] [PubMed]
    [Google Scholar]
  87. UniProt C. UNIPROT: A worldwide hub of protein knowledge. Nucleic Acids Res 2019; 47:D506–D515 [View Article]
    [Google Scholar]
  88. Wood TK, Knabel SJ, Kwan BW. Bacterial persister cell formation and dormancy. Appl Environ Microbiol 2013; 79:7116–7121 [View Article] [PubMed]
    [Google Scholar]
  89. Singh R, Ray P, Das A, Sharma M. Role of persisters and small-colony variants in antibiotic resistance of planktonic and biofilm-associated Staphylococcus aureus: an in vitro study. J Med Microbiol 2009; 58:1067–1073 [View Article] [PubMed]
    [Google Scholar]
  90. Van den Bergh B, Fauvart M, Michiels J. Formation, physiology, ecology, evolution and clinical importance of bacterial persisters. FEMS Microbiol Rev 2017; 41:219–251 [View Article] [PubMed]
    [Google Scholar]
  91. Balaban NQ, Merrin J, Chait R, Kowalik L, Leibler S. Bacterial persistence as a phenotypic switch. Science 2004; 305:1622–1625 [View Article] [PubMed]
    [Google Scholar]
  92. Conlon BP, Rowe SE, Gandt AB, Nuxoll AS, Donegan NP et al. Persister formation in Staphylococcus aureus is associated with ATP depletion. Nat Microbiol 2016; 1: [View Article] [PubMed]
    [Google Scholar]
  93. Cramton SE, Ulrich M, Gotz F, Doring G. Anaerobic conditions induce expression of polysaccharide intercellular adhesin in Staphylococcus aureus and Staphylococcus epidermidis. Infect Immun 2001; 69:4079–4085 [View Article] [PubMed]
    [Google Scholar]
  94. Fuchs S, Pane-Farre J, Kohler C, Hecker M, Engelmann S. Anaerobic gene expression in Staphylococcus aureus. J Bacteriol 2007; 189:4275–4289 [View Article] [PubMed]
    [Google Scholar]
  95. Vestergaard M, Nohr-Meldgaard K, Bojer MS, Krogsgard Nielsen C, Meyer RL et al. Inhibition of the ATP synthase eliminates the intrinsic resistance of Staphylococcus aureus towards Polymyxins. MBio 2017; 8: [View Article]
    [Google Scholar]
  96. Harrell LJ, Evans JB. Anaerobic resistance of clinical isolates of Staphylococcus aureus to aminoglycosides. Antimicrob Agents Chemother 1978; 14:927–929 [View Article] [PubMed]
    [Google Scholar]
  97. Ni Eidhin D, Perkins S, Francois P, Vaudaux P, Hook M et al. Clumping factor B (ClfB), a new surface-located fibrinogen-binding adhesin of Staphylococcus aureus. Mol Microbiol 1998; 30:245–257 [View Article] [PubMed]
    [Google Scholar]
  98. O’Brien L, Kerrigan SW, Kaw G, Hogan M, Penades J et al. Multiple mechanisms for the activation of human platelet aggregation by Staphylococcus aureus: roles for the clumping factors ClfA and ClfB, the serine-aspartate repeat protein SdrE and protein A. Mol Microbiol 2002; 44:1033–1044 [View Article] [PubMed]
    [Google Scholar]
  99. Wolz C, Goerke C, Landmann R, Zimmerli W, Fluckiger U. Transcription of clumping factor A in attached and unattached Staphylococcus aureus in vitro and during device-related infection. Infect Immun 2002; 70:2758–2762 [View Article] [PubMed]
    [Google Scholar]
  100. Haaber J, Cohn MT, Frees D, Andersen TJ, Ingmer H. Planktonic aggregates of staphylococcus aureus protect against common antibiotics. PLoS One 2012; 7:e41075 [View Article] [PubMed]
    [Google Scholar]
  101. George NPE, Wei Q, Shin PK, Konstantopoulos K, Ross JM. Staphylococcus aureus adhesion via SPA, CLFA, and SDRCDE to immobilized platelets demonstrates shear-dependent behavior. Arterioscler Thromb Vasc Biol 2006; 26:2394–2400 [View Article] [PubMed]
    [Google Scholar]
  102. Sullam PM, Bayer AS, Foss WM, Cheung AL. Diminished platelet binding in vitro by Staphylococcus aureus is associated with reduced virulence in a rabbit model of infective endocarditis. Infect Immun 1996; 64:4915–4921 [View Article] [PubMed]
    [Google Scholar]
  103. Kuroda M, Ohta T, Uchiyama I, Baba T, Yuzawa H et al. Whole genome sequencing of meticillin-resistant Staphylococcus aureus. Lancet 2001; 357:1225–1240 [View Article] [PubMed]
    [Google Scholar]
  104. Holden MT, Feil EJ, Lindsay JA, Peacock SJ, Day NP 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; 101:9786–9791 [View Article] [PubMed]
    [Google Scholar]
  105. Diep BA, Gill SR, Chang RF, Phan TH, Chen JH et al. Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus. Lancet 2006; 367:731–739 [View Article] [PubMed]
    [Google Scholar]
  106. Centers for Disease Control and Prevention (CDC) Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus - Minnesota and North Dakota, 1997-1999. MMWR Morb Mortal Wkly Rep 1999; 48:707–710 [PubMed]
    [Google Scholar]
  107. Nadkarni MA, Martin FE, Jacques NA, Hunter N. Determination of bacterial load by real-time PCR using a broad-range (universal) probe and primers set. Microbiology (Reading) 2002; 148:257–266 [View Article] [PubMed]
    [Google Scholar]
  108. Koprivnjak T, Mlakar V, Swanson L, Fournier B, Peschel A et al. Cation-induced transcriptional regulation of the DLT operon of Staphylococcus aureus. J Bacteriol 2006; 188:3622–3630 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000598
Loading
/content/journal/mgen/10.1099/mgen.0.000598
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Supplementary material 2

EXCEL

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error