Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 65

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Quorum Sensing and Toxin Production in Staphylococcus aureus Osteomyelitis: Pathogenesis and Paradox

Butrico, Casey E., Cassat, James E.·2020·Toxins
DOI 10.3390/toxins12080516
Open this paper in CoChat — free account

Abstract

Staphylococcus aureus is a Gram-positive pathogen capable of infecting nearly every vertebrate organ. Among these tissues, invasive infection of bone (osteomyelitis) is particularly common and induces high morbidity. Treatment of osteomyelitis is notoriously difficult and often requires debridement of diseased bone in conjunction with prolonged antibiotic treatment to resolve infection. During osteomyelitis, S. aureus forms characteristic multicellular microcolonies in distinct niches within bone. Virulence and metabolic responses within these multicellular microcolonies are coordinated, in part, by quorum sensing via the accessory gene regulator (agr) locus, which allows staphylococcal populations to produce toxins and adapt in response to bacterial density. During osteomyelitis, the Agr system significantly contributes to dysregulation of skeletal homeostasis and disease severity but may also paradoxically inhibit persistence in the host. Moreover, the Agr system is subject to complex crosstalk with other S. aureus regulatory systems, including SaeRS and SrrAB, which can significantly impact the progression of osteomyelitis. The objective of this review is to highlight Agr regulation, its implications on toxin production, factors that affect Agr activation, and the potential paradoxical influences of Agr regulation on disease progression during osteomyelitis.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3390/toxins12080516

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 3 references

Research works printed but not linked: 156

  1. Lew, 2004, Osteomyelitis, Lancet, 364, 369, 10.1016/S0140-6736(04)16727-5 · DOI · Paper page
  2. Harik, 2010, Management of acute hematogenous osteomyelitis in children, Expert Rev. Anti Infect. Ther., 8, 175, 10.1586/eri.09.130 · DOI
  3. Hatzenbuehler, 2011, Diagnosis and management of osteomyelitis, Am. Fam. Physician, 84, 1027
  4. Spagnolo, 1993, Chronic staphylococcal osteomyelitis: A new experimental rat model, Infect. Immun., 61, 5225, 10.1128/iai.61.12.5225-5230.1993 · doi:10.1128/iai.61.12.5225-5230.1993
  5. Power, 1990, A rat model of Staphylococcus aureus chronic osteomyelitis that provides a suitable system for studying the human infection, J. Med. Microbiol., 33, 189, 10.1099/00222615-33-3-189 · doi:10.1099/00222615-33-3-189
  6. Alderson, 1986, Acute haematogenous osteomyelitis and septic arthritis—A single disease. A hypothesis based upon the presence of transphyseal blood vessels, J. Bone Jt. Surg. Br., 68, 268, 10.1302/0301-620X.68B2.3958014 · doi:10.1302/0301-620x.68b2.3958014
  7. Cassat, 2013, A secreted bacterial protease tailors the Staphylococcus aureus virulence repertoire to modulate bone remodeling during osteomyelitis, Cell Host Microbe, 13, 759, 10.1016/j.chom.2013.05.003 · DOI · Paper page
  8. Hannan, 2009, Special considerations in the management of osteomyelitis defects (diabetes, the ischemic or dysvascular bed, and irradiation), Semin. Plast. Surg., 23, 132, 10.1055/s-0029-1214165 · doi:10.1055/s-0029-1214165
  9. Trombetta, 2017, Evidence of Staphylococcus aureus deformation, proliferation, and migration in canaliculi of live cortical bone in murine models of osteomyelitis, J. Bone Min. Res., 32, 985, 10.1002/jbmr.3055 · DOI · Paper page
  10. Lowy, 1998, Medical progress: Staphylococcus aureus infections, N. Engl. J. Med., 339, 520, 10.1056/NEJM199808203390806 · DOI · Paper page
  11. Kong, C., Neoh, H.M., and Nathan, S. (2016). Targeting staphylococcus aureus toxins: A potential form of anti-virulence therapy. Toxins, 8. · DOI · Paper page
  12. Brandis, 2017, Having your cake and eating it-Staphylococcus aureus small colony variants can evolve faster growth rate without losing their antibiotic resistance, Microb. Cell, 4, 275, 10.15698/mic2017.08.587 · doi:10.15698/mic2017.08.587
  13. Jenul, C., and Horswill, A.R. (2018). Regulation of Staphylococcus aureus virulence. Microbiol. Spectr., 6. · DOI
  14. Haag, 2017, The role of two-component signal transduction systems in Staphylococcus aureus virulence regulation, Curr. Top. Microbiol., 409, 145
  15. Stock, 2000, Two-component signal transduction, Annu. Rev. Biochem., 69, 183, 10.1146/annurev.biochem.69.1.183 · DOI · Paper page
  16. Steiner, 2018, Evidence of cross-regulation in two closely related pyruvate-sensing systems in uropathogenic Escherichia coli, J. Membr. Biol., 251, 65, 10.1007/s00232-018-0014-2 · DOI
  17. Boles, B.R., and Horswill, A.R. (2008). Agr-mediated dispersal of Staphylococcus aureus biofilms. PLoS Pathog., 4. · DOI · Paper page
  18. Sloan, 2019, Timing is everything: Impact of naturally occurring Staphylococcus aureus AgrC cytoplasmic domain adaptive mutations on autoinduction, J. Bacteriol., 201, 409, 10.1128/JB.00409-19 · doi:10.1128/jb.00409-19
  19. Lebeau, 1994, Coagulase expression in Staphylococcus aureus is positively and negatively modulated by an agr-dependent mechanism, J. Bacteriol., 176, 5534, 10.1128/jb.176.17.5534-5536.1994 · doi:10.1128/jb.176.17.5534-5536.1994
  20. Suligoy, C.M., Lattar, S.M., Noto Llana, M., Gonzalez, C.D., Alvarez, L.P., Robinson, D.A., Gomez, M.I., Buzzola, F.R., and Sordelli, D.O. (2018). Mutation of agr is associated with the adaptation of Staphylococcus aureus to the host during chronic osteomyelitis. Front. Cell Infect. Microbiol., 8. · DOI
  21. Voyich, 2009, The SaeR/S gene regulatory system is essential for innate immune evasion by Staphylococcus aureus, J. Infect. Dis., 199, 1698, 10.1086/598967 · DOI · Paper page
  22. Morrison, J.M., Anderson, K.L., Beenken, K.E., Smeltzer, M.S., and Dunman, P.M. (2012). The staphylococcal accessory regulator, SarA, is an RNA-binding protein that modulates the mRNA turnover properties of late-exponential and stationary phase Staphylococcus aureus cells. Front. Cell Infect. Microbiol., 2. · DOI
  23. Somerville, 2009, At the crossroads of bacterial metabolism and virulence factor synthesis in staphylococci, Microbiol. Mol. Biol. Rev., 73, 233, 10.1128/MMBR.00005-09 · DOI · Paper page
  24. Pragman, 2004, Characterization of virulence factor regulation by SrrAB, a two-component system in Staphylococcus aureus, J. Bacteriol., 186, 2430, 10.1128/JB.186.8.2430-2438.2004 · DOI · Paper page
  25. Wilde, A.D., Snyder, D.J., Putnam, N.E., Valentino, M.D., Hammer, N.D., Lonergan, Z.R., Hinger, S.A., Aysanoa, E.E., Blanchard, C., and Dunman, P.M. (2015). Bacterial hypoxic responses revealed as critical determinants of the host-pathogen outcome by TnSeq analysis of Staphylococcus aureus invasive infection. PLoS Pathog., 11. · DOI · Paper page
  26. Roux, 2014, CodY-mediated regulation of the Staphylococcus aureus Agr system integrates nutritional and population density signals, J. Bacteriol., 196, 1184, 10.1128/JB.00128-13 · DOI · Paper page
  27. Majerczyk, 2008, Staphylococcus aureus CodY negatively regulates virulence gene expression, J. Bacteriol., 190, 2257, 10.1128/JB.01545-07 · DOI · Paper page
  28. Ji, 1995, Cell density control of staphylococcal virulence mediated by an octapeptide pheromone, Proc. Natl. Acad. Sci. USA, 92, 12055, 10.1073/pnas.92.26.12055 · DOI · Paper page
  29. Novick, 1995, The agr P2 operon: An autocatalytic sensory transduction system in Staphylococcus aureus, Mol. Gen. Genet., 248, 446, 10.1007/BF02191645 · DOI · Paper page
  30. Rajasree, 2016, Conformational features of the Staphylococcus aureus AgrA-promoter interactions rationalize quorum-sensing triggered gene expression, Biochem. Biophys. Rep., 6, 124
  31. Vandenesch, 1991, A temporal signal, independent of agr, is required for hla but not spa transcription in Staphylococcus aureus, J. Bacteriol., 173, 6313, 10.1128/jb.173.20.6313-6320.1991 · DOI · Paper page
  32. Geisinger, 2006, Inhibition of rot translation by RNAIII, a key feature of agr function, Mol. Microbiol., 61, 1038, 10.1111/j.1365-2958.2006.05292.x · DOI · Paper page
  33. Morfeldt, 1995, Activation of alpha-toxin translation in Staphylococcus aureus by the trans-encoded antisense RNA, RNAIII, Embo. J., 14, 4569, 10.1002/j.1460-2075.1995.tb00136.x · DOI · Paper page
  34. Queck, 2008, RNAIII-independent target gene control by the Agr quorum-sensing system: Insight into the evolution of virulence regulation in Staphylococcus aureus, Mol. Cell, 32, 150, 10.1016/j.molcel.2008.08.005 · DOI · Paper page
  35. Arvidson, 2001, Regulation of virulence determinants in Staphylococcus aureus, Int. J. Med. Microbiol., 291, 159, 10.1078/1438-4221-00112 · DOI · Paper page
  36. Phonimdaen, 1988, Molecular cloning and expression of the coagulase gene of Staphylococcus aureus 8325-4, J. Gen. Microbiol., 134, 75
  37. Novick, 1993, Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule, Embo. J., 12, 3967, 10.1002/j.1460-2075.1993.tb06074.x · DOI · Paper page
  38. Patel, 1992, Regulation of the protein A-encoding gene in Staphylococcus aureus, Gene, 114, 25, 10.1016/0378-1119(92)90703-R · DOI
  39. Chabelskaya, 2014, Dual RNA regulatory control of a Staphylococcus aureus virulence factor, Nucleic. Acid, 42, 4847, 10.1093/nar/gku119 · DOI
  40. Liu, 2011, RNAIII activates map expression by forming an RNA-RNA complex in Staphylococcus aureus, Febs. Lett., 585, 899, 10.1016/j.febslet.2011.02.021 · DOI
  41. Huntzinger, 2005, Staphylococcus aureus RNAIII and the endoribonuclease III coordinately regulate spa gene expression, EMBO J., 24, 824, 10.1038/sj.emboj.7600572 · DOI · Paper page
  42. Gupta, 2015, RNAIII of the Staphylococcus aureus agr system activates global regulator MgrA by stabilizing mRNA, Proc. Natl. Acad. Sci. USA, 112, 14036, 10.1073/pnas.1509251112 · DOI
  43. Dunman, 2003, Global regulation of Staphylococcus aureus genes by Rot, J. Bacteriol., 185, 610, 10.1128/JB.185.2.610-619.2003 · DOI · Paper page
  44. Boisset, 2007, Staphylococcus aureus RNAIII coordinately represses the synthesis of virulence factors and the transcription regulator Rot by an antisense mechanism, Genes Dev., 21, 1353, 10.1101/gad.423507 · DOI · Paper page
  45. Gillaspy, 1995, Role of the accessory gene regulator (Agr) in pathogenesis of staphylococcal osteomyelitis, Infect. Immun., 63, 3373, 10.1128/iai.63.9.3373-3380.1995 · DOI · Paper page
  46. Blevins, 2003, Role of sarA in the Pathogenesis of Staphylococcus aureus musculoskeletal infection, Infect. Immun., 71, 516, 10.1128/IAI.71.1.516-523.2003 · DOI
  47. Hendrix, 2016, Repurposing the nonsteroidal anti-inflammatory drug diflunisal as an osteoprotective, antivirulence therapy for Staphylococcus aureus osteomyelitis, Antimicrob. Agents Chemother., 60, 5322, 10.1128/AAC.00834-16 · DOI
  48. Bouras, 2018, Staphylococcus aureus osteoarticular infections in children: An 8-year review of molecular microbiology, antibiotic resistance and clinical characteristics, J. Med. Microbiol., 67, 1753, 10.1099/jmm.0.000859 · DOI
  49. Koettnitz, 2018, Whole-genome comparison of high and low virulent Staphylococcus aureus isolates inducing implant-associated bone infections, Int. J. Med. Microbiol., 208, 505
  50. Masters, E.A., Salminen, A.T., Begolo, S., Luke, E.N., Barrett, S.C., Overby, C.T., Gill, A.L., de Mesy Bentley, K.L., Awad, H.A., and Gill, S.R. (2019). An in vitro platform for elucidating the molecular genetics of S. aureus invasion of the osteocyte lacuno-canalicular network during chronic osteomyelitis. Nanomedicine, 21. · DOI
  51. Kwiecinski, 2019, Biofilm formation by Staphylococcus aureus clinical isolates correlates with the infection type, Infect. Dis., 51, 446, 10.1080/23744235.2019.1593499 · doi:10.1080/23744235.2019.1593499
  52. Peschel, 2013, Phenol-soluble modulins and staphylococcal infection, Nat. Rev. Microbiol., 11, 667, 10.1038/nrmicro3110 · DOI · Paper page
  53. Chatterjee, 2013, Essential Staphylococcus aureus toxin export system, Nat. Med., 19, 364, 10.1038/nm.3047 · DOI · Paper page
  54. Rasigade, J.-P., Trouillet-Assant, S., Ferry, T., Diep, B.A., Sapin, A., Lhoste, Y., Ranfaing, J., Badiou, C., Bento, Y., and Bes, M. (2013). PSMs of hypervirulent Staphylococcus aureus act as intracellular toxins that kill infected osteoblasts. PLoS ONE, 8. · DOI
  55. Kretschmer, 2010, Human formyl peptide receptor 2 (FPR2/ALX) senses highly pathogenic Staphylococcus aureus, Cell Host Microbe., 7, 463, 10.1016/j.chom.2010.05.012 · DOI · Paper page
  56. Surewaard, 2013, Staphylococcal alpha-phenol soluble modulins contribute to neutrophil lysis after phagocytosis, Cell Microbiol., 15, 1427, 10.1111/cmi.12130 · DOI · Paper page
  57. Brandt, 2019, Innate immunity to Staphylococcus aureus: Evolving paradigms in soft tissue and invasive infection, J. Immunol., 200, 3871, 10.4049/jimmunol.1701574 · DOI
  58. Bhakdi, 1981, On the mechanism of membrane damage by Staphylococcus aureus a-Toxin, J. Cell Biol., 91, 83, 10.1083/jcb.91.1.83 · DOI · Paper page
  59. Ward, 1992, The Staphylococcus aureus α-toxin channel complex and the effect of Ca2+ ions on its interaction with lipid layers, J. Struct. Biol., 109, 129, 10.1016/1047-8477(92)90044-B · DOI
  60. Tobkes, 1985, Secondary structure and assembly mechanism of an oligomeric channel protein, Biochemistry, 24, 1915, 10.1021/bi00329a017 · DOI · Paper page
  61. Wilke, 2010, Role of a disintegrin and metalloprotease 10 in Staphylococcus aureus α-hemolysin-mediated cellular injury, Proc. Natl. Acad. Sci. USA, 107, 13473, 10.1073/pnas.1001815107 · DOI · Paper page
  62. Berube, 2013, Staphylococcus aureus α-toxin: Nearly a century of intrigue, Toxins, 5, 1140, 10.3390/toxins5061140 · DOI · Paper page
  63. Ma, 2017, Staphylococcus aureus α-toxin induces inflammatory cytokines via lysosomal acid sphingomyelinase and ceramides, Cell. Physiol. Biochem., 43, 2170, 10.1159/000484296 · DOI
  64. Craven, R.R., Gao, X., Allen, I.C., Gris, D., Bubeck Wardenburg, J., McElvania-TeKippe, E., Ting, J.P., and Duncan, J.A. (2009). Staphylococcus aureus α-hemolysin activates the NLRP3-inflammasome in human and mouse monocytic cells. PLoS ONE, 4. · DOI · Paper page
  65. Nilsson, 1999, Alpha-toxin and gamma-toxin jointly promote Staphylococcus aureus virulence in murine septic arthritis, Infect. Immun., 67, 1045, 10.1128/IAI.67.3.1045-1049.1999 · DOI
  66. Smith, 2018, A potential key role for alpha-haemolysin of Staphylococcus aureus in mediating chondrocyte death in septic arthritis, Bone Jt. Res., 7, 457, 10.1302/2046-3758.77.BJR-2017-0165.R1 · DOI
  67. Yoong, 2013, The effects of Staphylococcus aureus leukotoxins on the host: Cell lysis and beyond, Curr. Opin. Microbiol., 16, 63, 10.1016/j.mib.2013.01.012 · DOI
  68. Colin, 1994, Interaction of the two components of leukocidin from Staphylococcus aureus with human polymorphonuclear leukocyte membranes: Sequential binding and subsequent activation, Infect. Immun., 62, 3184, 10.1128/iai.62.8.3184-3188.1994 · DOI
  69. Menestrina, 2003, Ion channels and bacterial infection: The case of β-barrel pore-forming protein toxins of Staphylococcus aureus, FEBS Lett., 552, 54, 10.1016/S0014-5793(03)00850-0 · DOI
  70. Cré Mieux, A.-C., Dumitrescu, O., Lina, G., Vallee, C., Cote, J.-F., Muffat-Joly, M., Lilin, T., Etienne, J., Vandenesch, F., and Saleh-Mghir, A. (2019). Panton-Valentine leukocidin enhances the severity of community-associated methicillin-resistant Staphylococcus aureus rabbit osteomyelitis. PLoS ONE, 4. · DOI
  71. Holzinger, 2012, Staphylococcus aureus Panton-Valentine leukocidin induces an inflammatory response in human phagocytes via the NLRP3 inflammasome, J. Leukoc. Biol., 92, 1069, 10.1189/jlb.0112014 · DOI · Paper page
  72. Jiang, B., Wang, Y., Feng, Z., Xu, L., Zhao, S., Gong, Y., Zhang, C., Luo, X., Li, S., and Rao, X. (2017). Panton-Valentine leucocidin (PVL) as a potential indicator for prevalence, duration, and severity of Staphylococcus aureus osteomyelitis. Front. Microbiol., 8. · DOI
  73. Bocchini, 2006, Panton-Valentine leukocidin genes are associated with enhanced inflammatory response and local disease in acute hematogenous Staphylococcus aureus osteomyelitis in children, Pediatrics, 117, 433, 10.1542/peds.2005-0566 · DOI · Paper page
  74. Jin, 2013, Staphylococcal protein A, Panton-Valentine leukocidin and coagulase aggravate the bone loss and bone destruction in osteomyelitis, Cell Physiol. Biochem., 32, 322, 10.1159/000354440 · DOI
  75. Dohin, 2007, Pediatric bone and joint infections caused by Panton-Valentine leukocidin-positive Staphylococcus aureus, Pediatr. Infect. Dis. J., 26, 1042, 10.1097/INF.0b013e318133a85e · DOI · Paper page
  76. Tromp, 2018, Human CD45 is an f-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin, Nat. Microbiol., 3, 708, 10.1038/s41564-018-0159-x · DOI
  77. Löffler, B., Hussain, M., Grundmeier, M., Bruck, M., Holzinger, D., Varga, G., Roth, J., Kahl, B.C., Proctor, R.A., and Peter, G. (2010). Staphylococcus aureus Panton-Valentine leukocidin is a very potent cytotoxic factor for human neutrophils. PLoS Pathog., 6. · DOI · Paper page
  78. Dossett, 1969, RNAIII of the Staphylococcus aureus agr system activates global regulator MgrA by stabilizing mRNA, J. Immunol., 103, 1405, 10.4049/jimmunol.103.6.1405 · DOI · Paper page
  79. Kobayashi, S.D., and DeLeo, F.R. (2013). Staphylococcus aureus protein A promotes immune suppression. MBio, 4. · DOI
  80. Goodyear, 2003, Death by a B cell superantigen: In vivo VH-targeted apoptotic supraclonal B cell deletion by a staphylococcal toxin, J. Exp. Med., 197, 1125, 10.1084/jem.20020552 · DOI · Paper page
  81. Keener, 2017, Staphylococcus aureus protein A disrupts immunity mediated by long-lived plasma cells, J. Immunol., 198, 1263, 10.4049/jimmunol.1600093 · DOI
  82. Claro, T., Widaa, A., O’Seaghdha, M., Miajlovic, H., Foster, T.J., O’Brien, F.J., and Kerrigan, S.W. (2011). Staphylococcus aureus Protein A binds to osteoblasts and triggers signals that weaken bone in osteomyelitis. PLoS ONE, 6. · DOI · Paper page
  83. Claro, 2013, Staphylococcus aureus protein A binding to osteoblast tumour necrosis factor receptor 1 results in activation of nuclear factor kappa B and release of interleukin-6 in bone infection, Microbiology, 159, 147, 10.1099/mic.0.063016-0 · DOI
  84. Widaa, A., Claro, T., Foster, T.J., O’Brien, F.J., and Kerrigan, S.W. (2012). Staphylococcus aureus protein A plays a critical role in mediating bone destruction and bone loss in osteomyelitis. PLoS ONE, 7. · DOI · Paper page
  85. Delpino, 2016, Staphylococcus aureus protein A enhances osteoclastogenesis via TNFR1 and EGFR signaling, Biochim. Biophys. Acta, 1862, 1975, 10.1016/j.bbadis.2016.07.016 · DOI
  86. Chavakis, 2002, Staphylococcus aureus extracellular adherence protein serves as anti-inflammatory factor by inhibiting the recruitment of host leukocytes, Nat. Med., 8, 687, 10.1038/nm728 · DOI · Paper page
  87. Haggar, 2004, The extracellular adherence protein from Staphylococcus aureus inhibits neutrophil binding to endothelial cells, Infect. Immun., 72, 6164, 10.1128/IAI.72.10.6164-6167.2004 · DOI
  88. Lee, 2002, The Staphylococcus aureus Map protein is an immunomodulator that interferes with T cell-mediated responses, J. Clin. Investig., 110, 1461, 10.1172/JCI0216318 · DOI
  89. Wolz, 1996, Influence of agr on fibrinogen binding in Staphylococcus aureus Newman, Infect. Immun., 64, 3142, 10.1128/iai.64.8.3142-3147.1996 · DOI
  90. Xue, 2012, Rot and Agr system modulate fibrinogen-binding ability mainly by regulating clfB expression in Staphylococcus aureus NCTC8325, Med. Microbiol. Immunol., 201, 81, 10.1007/s00430-011-0208-z · DOI
  91. Dunman, 2001, Transcription profiling-based identification of Staphylococcus aureus genes regulated by the agr and/or sarA loci, J. Bacteriol., 183, 7341, 10.1128/JB.183.24.7341-7353.2001 · DOI · Paper page
  92. Cunningham, 1996, Clinical and molecular aspects of the pathogenesis of Staphylococcus aureus bone and joint infections, J. Med. Microbiol., 44, 157, 10.1099/00222615-44-3-157 · DOI
  93. Panizzi, 2006, Fibrinogen substrate recognition by staphylocoagulase (pro)thrombin complexes, J. Biol. Chem., 281, 1179, 10.1074/jbc.M507956200 · DOI
  94. Cheng, A.G., McAdow, M., Kim, H.K., Bae, T., Missiakas, D.M., and Schneewind, O. (2010). Contribution of coagulases towards Staphylococcus aureus disease and protective immunity. PLoS Pathog., 6. · DOI · Paper page
  95. Guggenberger, C., Wolz, C., Morrissey, J.A., and Heesemann, J. (2012). Two distinct coagulase-dependent barriers protect Staphylococcus aureus from neutrophils in a three dimensional in vitro infection model. PLoS Pathog., 8. · DOI
  96. Thomas, S., Liu, W., Arora, S., Ganesh, V., Ko, Y.-P., and Hook, M. (2019). The complex fibrinogen interactions of the Staphylococcus aureus coagulases. Front. Cell Infect. Microbiol., 9. · DOI
  97. Dufour, 2002, High genetic variability of the agr locus in Staphylococcus species, J. Bacteriol., 184, 1180, 10.1128/jb.184.4.1180-1186.2002 · DOI · Paper page
  98. Jarraud, 2000, Exfoliatin-producing strains define a fourth agr specificity group in Staphylococcus aureus, J. Bacteriol., 182, 6517, 10.1128/JB.182.22.6517-6522.2000 · DOI · Paper page
  99. Guangyong, 1997, Bacterial interference caused by autoinducing peptide variants, Science, 27, 2027
  100. Zhang, 2004, Identification of a staphylococcal AgrB segment(s) responsible for group-specific processing of AgrD by gene swapping, J. Bacteriol., 186, 6706, 10.1128/JB.186.20.6706-6713.2004 · doi:10.1128/jb.186.20.6706-6713.2004
  101. Nair, 2014, Impact of Staphylococcus aureus on pathogenesis in polymicrobial infections, Infect. Immune., 82, 2162, 10.1128/IAI.00059-14 · DOI
  102. Paharik, 2017, Coagulase-negative Staphylococcal strain prevents Staphylococcus aureus colonization and skin infection by blocking quorum sensing, Cell Host Microbe, 22, 746, 10.1016/j.chom.2017.11.001 · DOI · Paper page
  103. Oliveira, 2018, Outcomes and risk factors for polymicrobial posttraumatic osteomyelitis, J. Bone Joint. Infect., 3, 20, 10.7150/jbji.22566 · DOI
  104. Matias, 2018, Polymicrobial interactions influence the agr copy number in Staphylococcus aureus isolates from diabetic foot ulcers, Antonie Van Leeuwenhoek, 111, 2225, 10.1007/s10482-018-1103-z · DOI
  105. Todd, O.A., and Peters, B.M. (2019). Candida albicans and Staphylococcus aureus pathogenicity and polymicrobial interactions: Lessons beyond Koch’s postulates. J. Fungi., 5. · DOI
  106. Shopsin, 2008, Prevalence of agr dysfunction among colonizing Staphylococcus aureus strains, J. Infect. Dis., 198, 1171, 10.1086/592051 · DOI
  107. Traber, 2008, Agr function in clinical Staphylococcus aureus isolates, Microbiology, 154, 2265, 10.1099/mic.0.2007/011874-0 · DOI · Paper page
  108. Schweizer, 2011, Increased mortality with accessory gene regulator (agr) dysfunction in Staphylococcus aureus among bacteremic patients, Antimicrob. Agents Chemother., 55, 1082, 10.1128/AAC.00918-10 · DOI
  109. Altman, D.R., Sullivan, M.J., Chacko, K.I., Balasubramanian, D., Pak, T.R., Sause, W.E., Kumar, K., Sebra, R., Deikus, G., and Attie, O. (2018). Genome plasticity of agr-defective Staphylococcus aureus during clinical infection. Infect. Immun., 86. · DOI
  110. Gor, V., Takemura, A.J., Nishitani, M., Higashide, M., Medrano Romero, V., Ohniwa, R.L., and Morikawa, K. (2019). Finding of Agr phase variants in Staphylococcus aureus. MBio, 10. · DOI
  111. Buckling, 2005, Clonal distribution and phase-variable expression of a major histocompatibility complex analogue protein in Staphylococcus aureus, J. Bacteriol., 187, 2917, 10.1128/JB.187.8.2917-2919.2005 · DOI
  112. Traber, 2006, A slipped-mispairing mutation in AgrA of laboratory strains and clinical isolates results in delayed activation of agr and failure to translate δ- and α-haemolysins, Mol. Microbiol., 59, 1519, 10.1111/j.1365-2958.2006.04986.x · DOI
  113. Cheng, 2011, A play in four acts: Staphylococcus aureus abscess formation, Trends Microbiol., 19, 225, 10.1016/j.tim.2011.01.007 · DOI · Paper page
  114. Carnes, 2010, Confinement-induced quorum sensing of individual Staphylococcus aureus bacteria, Nat. Chem. Biol., 6, 41, 10.1038/nchembio.264 · DOI · Paper page
  115. Kolar, 2013, Extracellular proteases are key mediators of Staphylococcus aureus virulence via the global modulation of virulence-determinant stability, Microbiologyopen, 2, 18, 10.1002/mbo3.55 · DOI · Paper page
  116. Fowler, 2004, Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunction and low-level in vitro resistance to thrombin-induced platelet microbicidal protein, JID, 190, 1140, 10.1086/423145 · DOI · Paper page
  117. Paulander, W., Varming, A.N., Bæk, K.T., Haaber, J., Frees, D., and Ingmer, H. (2012). Antibiotic-mediated selection of quorum-sensing-negative Staphylococcus aureus. Mbio, 3. · DOI
  118. He, 2019, Resistance to leukocytes ties benefits of quorum sensing dysfunctionality to biofilm infection, Nat. Microbiol., 4, 1114, 10.1038/s41564-019-0413-x · DOI
  119. Nakamura, Y., Takahashi, H., Takaya, A., Inoue, Y., Katayama, Y., Kusuya, Y., Shoji, T., Takada, S., Nakagawa, S., and Oguma, R. (2020). Staphylococcus Agr virulence is critical for epidermal colonization and associates with atopic dermatitis development. Sci. Transl. Med., 12. · DOI
  120. Periasamy, 2012, How Staphylococcus aureus biofilms develop their characteristic structure, Proc. Natl. Acad. Sci. USA, 109, 1281, 10.1073/pnas.1115006109 · DOI · Paper page
  121. Sully, E.K., Malachowa, N., Elmore, B.O., Alexander, S.M., Femling, J.K., Gray, B.M., DeLeo, F.R., Otto, M., Cheung, A.L., and Edwards, B.S. (2014). Selective chemical inhibition of agr quorum sensing in Staphylococcus aureus promotes host defense with minimal impact on resistance. PLoS Pathog., 10. · DOI · Paper page
  122. Gray, 2013, Targeting agr- and agr-like quorum sensing systems for development of common therapeutics to treat multiple gram-positive bacterial infections, Sensors, 13, 5130, 10.3390/s130405130 · DOI · Paper page
  123. Khodaverdian, 2013, Discovery of antivirulence agents against methicillin-resistant Staphylococcus aureus, Antimicrob. Agents Chemother., 57, 3645, 10.1128/AAC.00269-13 · DOI
  124. Spoonmore, T.J., Ford, C.A., Curry, J.M., Guelcher, S.A., and Cassat, J.E. (2020). Concurrent local delivery of diflunisal limits bone destruction but fails to improve systemic vancomycin efficacy during Staphylococcus aureus osteomyelitis. Antimicrob. Agents Chemother., 64. · doi:10.1128/aac.00182-20
  125. Nakayama, 2009, Ambuic acid inhibits the biosynthesis of cyclic peptide quormones in gram-positive bacteria, Antimicrob. Agents Chemother., 53, 580, 10.1128/AAC.00995-08 · DOI
  126. Li, 2011, Lactobacillus reuteri-produced cyclic dipeptides quench Agr-mediated expression of toxic shock syndrome toxin-1 in staphylococci, Proc. Natl. Acad. Sci. USA, 108, 3360, 10.1073/pnas.1017431108 · DOI · Paper page
  127. Brown, M.M., Kwiecinski, J.M., Cruz, L.M., Shahbandi, A., Todd, D.A., Cech, N.B., and Horswill, A.R. (2020). Novel peptide from commensal Staphylococcus simulans blocks methicillin-resistant Staphylococcus aureus quorum sensing and protects host skin from damage. Antimicrob. Agents Chemother., 64. · DOI
  128. Valour, 2015, Delta-toxin production deficiency in Staphylococcus aureus: A diagnostic marker of bone and joint infection chronicity linked with osteoblast invasion and biofilm formation, Clin. Microbiol. Infect., 21, e1, 10.1016/j.cmi.2015.01.026 · DOI
  129. Tiwari, N., López-Redondo, M., Miguel-Romero, L., Kulhankova, K., Cahill, M.P., Tran, P.M., Kinney, K.J., Kilgore, S.H., Al-Tameemi, H., and Herfst, C.A. (Proc. Natl. Acad. Sci. USA, 2020). The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines, Proc. Natl. Acad. Sci. USA. · DOI · Paper page
  130. Mashruwala, A.A., van de Guchte, A., and Boyd, J.M. (2017). Impaired respiration elicits SrrAB-dependent programmed cell lysis and biofilm formation in Staphylococcus aureus. Elife, 6. · DOI · Paper page
  131. Mashruwala, A.A., Gries, C.M., Scherr, T.D., Kielian, T., and Boyd, J.M. (2017). SaeRS is responsive to cellular respiratory status and regulates fermentative biofilm formation in Staphylococcus aureus. Infect. Immun., 85. · DOI · Paper page
  132. Beenken, K.E., Mrak, L.N., Griffin, L.M., Zielinska, A.K., Shaw, L.N., Rice, K.C., Horswill, A.R., Bayles, K.W., and Smeltzer, M.S. (2010). Epistatic relationships between sarA and agr in Staphylococcus aureus biofilm formation. PLoS ONE, 5. · DOI · Paper page
  133. Cheung, 1992, Regulation of exoprotein expression in Staphylococcus aureus by a locus (sar) distinct from agr, Proc. Natl. Acad. Sci. USA, 89, 6462, 10.1073/pnas.89.14.6462 · DOI · Paper page
  134. Cheung, 1994, Cloning and sequencing of sarA of Staphylococcus aureus, a gene required for the expression of agr, J. Bacteriol., 176, 4168, 10.1128/jb.176.13.4168-4172.1994 · DOI · Paper page
  135. Chien, 1998, SarA level is a determinant of agr activation in Staphylococcus aureus, Mol. Microbiol., 30, 991, 10.1046/j.1365-2958.1998.01126.x · DOI
  136. Reyes, 2011, Coordinated regulation by AgrA, SarA, and SarR to control agr expression in Staphylococcus aureus, J. Bacteriol., 193, 6020, 10.1128/JB.05436-11 · DOI · Paper page
  137. Zielinska, 2011, Defining the strain-dependent impact of the staphylococcal accessory regulator (sarA) on the alpha-toxin phenotype of Staphylococcus aureus, J. Bacteriol., 193, 2948, 10.1128/JB.01517-10 · DOI
  138. Lindsay, 1999, Interactive regulatory pathways control virulence determinant production and stability in response to environmental conditions in Staphylococcus aureus, Mol. Gen. Genet., 262, 323, 10.1007/s004380051090 · DOI
  139. Loughran, 2016, Impact of sarA and phenol-soluble modulins on the pathogenesis of osteomyelitis in diverse clinical isolates of Staphylococcus aureus, Infect. Immun., 84, 2586, 10.1128/IAI.00152-16 · DOI
  140. Zielinska, 2012, SarA-mediated repression of protease production plays a key role in the pathogenesis of Staphylococcus aureus USA300 isolates, Mol. Microbiol., 86, 1183, 10.1111/mmi.12048 · DOI · Paper page
  141. Sun, 2010, In the Staphylococcus aureus two-component system sae, the response regulator SaeR Binds to a direct repeat sequence and DNA binding requires phosphorylation by the sensor kinase SaeS, J. Bacteriol., 192, 2111, 10.1128/JB.01524-09 · DOI
  142. Jeong, 2012, The auxiliary protein complex SaePQ activates the phosphatase activity of sensor kinase SaeS in the SaeRS two-component system of Staphylococcus aureus, Mol. Microbiol., 86, 331, 10.1111/j.1365-2958.2012.08198.x · DOI · Paper page
  143. Geiger, 2008, The virulence regulator Sae of Staphylococcus aureus: Promoter activities and response to phagocytosis-related signals, J. Bacteriol., 190, 3419, 10.1128/JB.01927-07 · DOI · Paper page
  144. Cho, H., Jeong, D.W., Liu, Q., Yeo, W.-S., Vogl, T., Skaar, E.P., Chazen, W.J., and Bae, T. (2015). Calprotectin increases the activity of the SaeRS two component system and murine mortality during Staphylococcus aureus infections. PLoS Pathog., 11. · DOI · Paper page
  145. Weinrick, 2004, Effect of mild acid on gene expression in Staphylococcus aureus, J. Bacteriol., 186, 8407, 10.1128/JB.186.24.8407-8423.2004 · DOI · Paper page
  146. Geiger, T., Francois, P., Liebeke, M., Fraunholz, M., Goerke, C., Krismer, B., Schrenzel, J., Lalk, M., and Wolz, C. (2012). The stringent response of Staphylococcus aureus and its impact on survival after phagocytosis through the induction of intracellular PSMs expression. PLoS Path., 8. · DOI · Paper page
  147. Pohl, 2009, CodY in Staphylococcus aureus: A regulatory link between metabolism and virulence gene expression, J. Bacteriol., 191, 2953, 10.1128/JB.01492-08 · DOI · Paper page
  148. Majerczyk, 2010, Direct targets of CodY in Staphylococcus aureus, J. Bacteriol., 192, 2861, 10.1128/JB.00220-10 · DOI · Paper page
  149. Seidl, 2006, Staphylococcus aureus CcpA affects virulence determinant production and antibiotic resistance, Antimicrob. Agents Chemother., 50, 1183, 10.1128/AAC.50.4.1183-1194.2006 · DOI · Paper page
  150. Esen, 2014, Aerobic glycolysis in osteoblasts, Curr. Osteoporos. Rep., 12, 433, 10.1007/s11914-014-0235-y · DOI
  151. Kim, 2007, Osteoclast precursors display dynamic metabolic shifts toward accelerated glucose metabolism at an early stage of RANKL-stimulated osteoclast differentiation, Cell Physiol. Biochem., 20, 935, 10.1159/000110454 · DOI
  152. Bischoff, M., Wonnenberg, B., Nippe, N., Nyffenegger-Jann, N.J., Voss, M., Beisswenger, C., Sunderkotter, C., Molle, V., Dinh, Q.T., and Lammert, F. (2017). CcpA affects infectivity of Staphylococcus aureus in a hyperglycemic environment. Front. Cell Infect. Microbiol., 7. · DOI · Paper page
  153. Harper, L., Balasubramanian, D., Ohneck, E.A., Sause, W.E., Chapman, J., Mejia-Sosa, B., Lhakhang, T., Heguy, A., Tsirigos, A., and Ueberheide, B. (2018). Staphylococcus aureus responds to the central metabolite pyruvate to regulate virulence. MBio, 9. · DOI
  154. Ky, L., and Otto, M. (2015). Quorum-sensing regulation in staphylococci-an overview. Front. Microbiol., 6. · DOI · Paper page
  155. Mlynek, K.D., Sause, W.E., Moormeier, D.E., Sadykov, M.R., Hill, K.R., Torres, V.J., Bayles, K.W., and Brinsmade, S.R. (2018). Nutritional regulation of the Sae two-component system by CodY in Staphylococcus aureus. J. Bacteriol., 200. · DOI · Paper page
  156. Bronner, 2000, Variable expressions of Staphylococcus aureus bicomponent leucotoxins semiquantified by competitive reverse transcription-PCR, Appl. Environ. Microbiol., 66, 3931, 10.1128/AEM.66.9.3931-3938.2000 · DOI

Cited by

See all 65

Metadata

Authors
Butrico, C. E., & Cassat, J. E.
Venue
Toxins
Publisher
MDPI AG
Published
2020-08-12
Volume
12
Issue
8
Pages
516
ISSN
2072-6651
DOI
10.3390/toxins12080516
Cited by
65
References
3
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • National Institute of Allergy and Infectious Diseases (R01AI132560, T32AI11254)
  • Burroughs Wellcome Fund (1013348)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Quorum Sensing and Toxin Production in Staphylococcus aureus Osteomyelitis: Pathogenesis and Paradox. https://app.cochat.ai/papers/10.3390/toxins12080516
The paper
Butrico, C. E., & Cassat, J. E. (2020). Quorum Sensing and Toxin Production in Staphylococcus aureus Osteomyelitis: Pathogenesis and Paradox. Toxins. https://doi.org/10.3390/toxins12080516

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.