FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
PloS one2019; 14(8); e0221012; doi: 10.1371/journal.pone.0221012

Equine or porcine synovial fluid as a novel ex vivo model for the study of bacterial free-floating biofilms that form in human joint infections.

Abstract: Bacterial invasion of synovial joints, as in infectious or septic arthritis, can be difficult to treat in both veterinary and human clinical practice. Biofilms, in the form of free-floating clumps or aggregates, are involved with the pathogenesis of infectious arthritis and periprosthetic joint infection (PJI). Infection of a joint containing an orthopedic implant can additionally complicate these infections due to the presence of adherent biofilms. Because of these biofilm phenotypes, bacteria within these infected joints show increased antimicrobial tolerance even at high antibiotic concentrations. To date, animal models of PJI or infectious arthritis have been limited to small animals such as rodents or rabbits. Small animal models, however, yield limited quantities of synovial fluid making them impractical for in vitro research. Herein, we describe the use of ex vivo equine and porcine models for the study of synovial fluid induced biofilm aggregate formation and antimicrobial tolerance. We observed Staphylococcus aureus and other bacterial pathogens adapt the same biofilm aggregate phenotype with significant antimicrobial tolerance in both equine and porcine synovial fluid, analogous to human synovial fluid. We also demonstrate that enzymatic dispersal of synovial fluid aggregates restores the activity of antimicrobials. Future studies investigating the interaction of bacterial cell surface proteins with host synovial fluid proteins can be readily carried out in equine or porcine ex vivo models to identify novel drug targets for treatment of prevention of these difficult to treat infectious diseases.
Get Full Text
Publication Date: 2019-08-15 PubMed ID: 31415623PubMed Central: PMC6695105DOI: 10.1371/journal.pone.0221012Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study introduces the use of equine and porcine models as a novel approach to understanding bacterial biofilm formation in human joint infections, which tend to show a high tolerance to antimicrobial treatment. These models could potentially identify new drug targets for countering these infections.

Background and Challenges

  • Septic arthritis and periprosthetic joint infection (PJI) occur when bacteria invade synovial joints. These bacteria often form biofilms, which are essentially bacterial colonies encapsulated in a protective layer. This biofilm formation elevates the resistance of bacteria to antibiotics and makes these infections difficult to treat.
  • Till date, the commonly used animal models for studying such infections are small animals like rodents or rabbits. However, due to their size, these yield limited volumes of synovial fluid, which is impractical for laboratory study.

New Models for Biofilm Study

  • The research discusses the use of equine and porcine models as they produce a significant amount of synovial fluid, allowing for effective in vitro study.
  • It was observed that Staphylococcus aureus and other bacterial pathogens adapt the same biofilm aggregate phenotype (or form) in equine and porcine synovial fluid, similar to that seen in human synovial fluid, showing significant antimicrobial tolerance.
  • This suggests that bacterial reactions in equine and porcine models likely mirror those in human joints, making them a useful tool for research.

Enzymatic Dispersal of Biofilms

  • The study further provides evidence that enzymatic dispersal of synovial fluid aggregates can reactivate the effectiveness of antimicrobials, showing a potential pathway for therapy.

Implications and Future Research

  • This study paves the way for more in-depth research on bacterial cell surface proteins’ interaction with host synovial fluid proteins using equine or porcine models.
  • Such investigation has the potential to identify new targets for drug development, specifically aimed at preventing and treating challenging joint infections in both veterinary and human clinical practice.

Cite This Article

APA
Gilbertie JM, Schnabel LV, Hickok NJ, Jacob ME, Conlon BP, Shapiro IM, Parvizi J, Schaer TP. (2019). Equine or porcine synovial fluid as a novel ex vivo model for the study of bacterial free-floating biofilms that form in human joint infections. PLoS One, 14(8), e0221012. https://doi.org/10.1371/journal.pone.0221012

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 14
Issue: 8
Pages: e0221012

Researcher Affiliations

Gilbertie, Jessica M
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States of America.
  • Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States of America.
  • Department of Clinical Studies New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, United States of America.
Schnabel, Lauren V
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States of America.
  • Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States of America.
Hickok, Noreen J
  • Department of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, PA, United States of America.
Jacob, Megan E
  • Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States of America.
  • Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America.
Conlon, Brian P
  • Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, NC, United States of America.
Shapiro, Irving M
  • Department of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, PA, United States of America.
Parvizi, Javad
  • Department of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, PA, United States of America.
Schaer, Thomas P
  • Department of Clinical Studies New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, United States of America.

MeSH Terms

  • Animals
  • Arthritis / microbiology
  • Arthritis / pathology
  • Biofilms / growth & development
  • Disease Models, Animal
  • Horses
  • Humans
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / pathology
  • Staphylococcus aureus / physiology
  • Swine
  • Synovial Fluid / microbiology

Grant Funding

  • R01 AI137273 / NIAID NIH HHS
  • R01 AR072513 / NIAMS NIH HHS

Conflict of Interest Statement

The authors have declared that no competing interests exist.

References

This article includes 82 references
  1. Tong SYCC, Davis JS, Eichenberger E, Holland TL, Fowler VG. Staphylococcus aureus infections: Epidemiology, pathophysiology, clinical manifestations, and management.. Clin Microbiol Rev 2015;28: 603–661.
    doi: 10.1128/CMR.00134-14pmc: PMC4451395pubmed: 26016486google scholar: lookup
  2. Mathews CJ, Weston VC, Jones A, Field M, Coakley G. Bacterial septic arthritis in adults.. Lancet 2010;375: 846–855.
    doi: 10.1016/S0140-6736(09)61595-6pubmed: 20206778google scholar: lookup
  3. Shirtliff ME, Mader JT. Acute septic arthritis.. Clin Microbiol Rev 2002;15: 527–544.
    doi: 10.1128/CMR.15.4.527-544.2002pmc: PMC126863pubmed: 12364368google scholar: lookup
  4. Pulido L, Ghanem E, Joshi A, Purtill JJ, Parvizi J. Periprosthetic joint infection: The incidence, timing, and predisposing factors.. Clin Orthop Relat Res 2008;466: 1710–1715.
    doi: 10.1007/s11999-008-0209-4pmc: PMC2505241pubmed: 18421542google scholar: lookup
  5. Tande AJ, Patel R. Prosthetic joint infection.. Clin Microbiol Rev 2014;27: 302–345.
    doi: 10.1128/CMR.00111-13pmc: PMC3993098pubmed: 24696437google scholar: lookup
  6. Lora-Tamayo J, Murillo O, Iribarren JA, Soriano A, Sánchez-Somolinos M, Baraia-Etxaburu JM. A Large Multicenter Study of Methicillin–Susceptible and Methicillin–Resistant Staphylococcus aureus Prosthetic Joint Infections Managed With Implant Retention.. Clin Infect Dis 2013;56: 182–194.
    doi: 10.1093/cid/cis746pubmed: 22942204google scholar: lookup
  7. Otto M. Staphylococcal biofilms.. Curr Top Microbiol Immunol 2008;322: 207–28.
    pmc: PMC2777538pubmed: 18453278
  8. McConoughey SJ, Howlin R, Granger JF, Manring MM, Calhoun JH, Shirtliff M. Biofilms in periprosthetic orthopedic infections.. Future Microbiol 2014;9: 987–1007.
    doi: 10.2217/fmb.14.64pmc: PMC4407677pubmed: 25302955google scholar: lookup
  9. Zimmerli W, Moser C. Pathogenesis and treatment concepts of orthopaedic biofilm infections.. FEMS Immunol Med Microbiol 2012;65: 158–168.
    doi: 10.1111/j.1574-695X.2012.00938.xpubmed: 22309166google scholar: lookup
  10. Zimmerli W, Sendi P. Orthopaedic biofilm infections.. APMIS 2017;125: 353–364.
    doi: 10.1111/apm.12687pubmed: 28407423google scholar: lookup
  11. Hall-Stoodley L, Stoodley P. Evolving concepts in biofilm infections.. Cell Microbiol 2009;11: 1034–1043.
    doi: 10.1111/j.1462-5822.2009.01323.xpubmed: 19374653google scholar: lookup
  12. Bjarnsholt T, Alhede M, Alhede M, Eickhardt-Sørensen SR, Moser C, Kühl M. The in vivo biofilm.. Trends Microbiol 2013;21: 466–474.
    doi: 10.1016/j.tim.2013.06.002pubmed: 23827084google scholar: lookup
  13. Alhede M, Kragh KN, Qvortrup K, Allesen-Holm M, van Gennip M, Christensen LD. Phenotypes of non-attached Pseudomonas aeruginosa aggregates resemble surface attached biofilm.. PLoS One 2011;6: e27943.
    doi: 10.1371/journal.pone.0027943pmc: PMC3221681pubmed: 22132176google scholar: lookup
  14. Burmølle M, Thomsen TR, Fazli M, Dige I, Christensen L, Homøe P. Biofilms in chronic infections—A matter of opportunity—Monospecies biofilms in multispecies infections.. FEMS Immunol Med Microbiol 2010;59: 324–336.
    doi: 10.1111/j.1574-695X.2010.00714.xpubmed: 20602635google scholar: lookup
  15. Kragh KN, Hutchison JB, Melaugh G, Rodesney C, Roberts AEL, Irie Y. Role of Multicellular Aggregates in Biofilm Formation.. MBio 2016;7: e00237.
    doi: 10.1128/mBio.00237-16pmc: PMC4807362pubmed: 27006463google scholar: lookup
  16. Tremblay YDN, Labrie J, Chénier S, Jacques M. Actinobacillus pleuropneumoniae grows as aggregates in the lung of pigs: is it time to refine our in vitro biofilm assays?. Microb Biotechnol 2017;10: 756–760.
    doi: 10.1111/1751-7915.12432pmc: PMC5481545pubmed: 27790837google scholar: lookup
  17. Dastgheyb S, Parvizi J, Shapiro IM, Hickok NJ, Otto M. Effect of biofilms on recalcitrance of staphylococcal joint infection to antibiotic treatment.. J Infect Dis 2015;211: 641–650.
    doi: 10.1093/infdis/jiu514pmc: PMC4318921pubmed: 25214518google scholar: lookup
  18. Dastgheyb SS, Villaruz AE, Le KY, Tan VY, Duong AC, Chatterjee SS. Role of phenol-soluble modulins in formation of Staphylococcus aureus biofilms in synovial fluid.. Infect Immun 2015;83: 2966–2975.
    doi: 10.1128/IAI.00394-15pmc: PMC4468530pubmed: 25964472google scholar: lookup
  19. Dastgheyb SS, Hammoud S, Ketonis C, Liu AY, Fitzgerald K, Parvizi J. Staphylococcal persistence due to biofilm formation in synovial fluid containing prophylactic cefazolin.. Antimicrob Agents Chemother 2015;59: 2122–2128.
    doi: 10.1128/AAC.04579-14pmc: PMC4356782pubmed: 25624333google scholar: lookup
  20. Perez K, Patel R. Biofilm-like aggregation of Staphylococcus epidermidis in synovial fluid.. J Infect Dis 2015;212: 335–336.
    doi: 10.1093/infdis/jiv096pmc: PMC4566000pubmed: 25712965google scholar: lookup
  21. Post JC. Direct Evidence of Bacterial Biofilms in Otitis Media.. Laryngoscope 2001;111: 2083–2094.
    doi: 10.1097/00005537-200112000-00001pubmed: 11802002google scholar: lookup
  22. Bay L, Kragh KN, Eickhardt SR, Poulsen SS, Gjerdrum LMR, Ghathian K. Bacterial Aggregates Establish at the Edges of Acute Epidermal Wounds.. Adv wound care 2018;7: 105–113.
    doi: 10.1089/wound.2017.0770pmc: PMC5905854pubmed: 29675336google scholar: lookup
  23. Landry RM, An D, Hupp JT, Singh PK, Parsek MR. Mucin-Pseudomonas aeruginosa interactions promote biofilm formation and antibiotic resistance.. Mol Microbiol 2006;59: 142–151.
    doi: 10.1111/j.1365-2958.2005.04941.xpubmed: 16359324google scholar: lookup
  24. Stewart PS. Antimicrobial Tolerance in Biofilms.. Microb Biofilms, 2nd Ed 2015;3: 269–285.
    doi: 10.1128/microbiolspec.MB-0010-2014pmc: PMC4507308pubmed: 26185072google scholar: lookup
  25. Corrado A, Donato P, MacCari S, Cecchi R, Spadafina T, Arcidiacono L. Staphylococcus aureus-dependent septic arthritis in murine knee joints: Local immune response and beneficial effects of vaccination.. Sci Rep 2016;6: 38043.
    doi: 10.1038/srep38043pmc: PMC5128924pubmed: 27901071google scholar: lookup
  26. Wang Y, Cheng LI, Helfer DR, Ashbaugh AG, Miller RJ, Tzomides AJ. Mouse model of hematogenous implant-related Staphylococcus aureus biofilm infection reveals therapeutic targets.. Proc Natl Acad Sci 2017;114: 201703427.
    doi: 10.1073/pnas.1703427114pmc: PMC5495257pubmed: 28607050google scholar: lookup
  27. Aigner T, Cook JL, Gerwin N, Glasson SS, Laverty S, Little CB. Histopathology atlas of animal model systems—overview of guiding principles.. Osteoarthr Cartil 2010;18: S2–6.
    doi: 10.1016/j.joca.2010.07.013pubmed: 20864020google scholar: lookup
  28. Moran CJ, Ramesh A, Brama PAJ, O JM, O FJ, O’Byrne JM. The benefits and limitations of animal models for translational research in cartilage repair.. J Exp Orthop 2016;3: 1.
    doi: 10.1186/s40634-015-0037-xpmc: PMC4703594pubmed: 26915001google scholar: lookup
  29. Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W. Genomic responses in mouse models poorly mimic human inflammatory diseases.. Proc Natl Acad Sci 2013;110: 3507–3512.
    doi: 10.1073/pnas.1222878110pmc: PMC3587220pubmed: 23401516google scholar: lookup
  30. Mage RG, Esteves PJ, Rader C. Rabbit models of human diseases for diagnostics and therapeutics development.. Dev Comp Immunol 2019;92: 99–104.
    doi: 10.1016/j.dci.2018.10.003pmc: PMC6364550pubmed: 30339876google scholar: lookup
  31. Barton NJ, Stevens DA, Hughes JP, Rossi AG, Chessell IP, Reeve AJ. Demonstration of a novel technique to quantitatively assess inflammatory mediators and cells in rat knee joints.. J Inflamm (Lond) 2007;4: 13.
    doi: 10.1186/1476-9255-4-13pmc: PMC1919375pubmed: 17567894google scholar: lookup
  32. Seifer DR, Furman BD, Guilak F, Olson SA, Brooks SC, Kraus VB. Novel synovial fluid recovery method allows for quantification of a marker of arthritis in mice.. Osteoarthr Cartil 2008;16: 1532–8.
    doi: 10.1016/j.joca.2008.04.013pmc: PMC2602808pubmed: 18538588google scholar: lookup
  33. Wayne Mcilwraith C, Fortier LA, Frisbie DD, Nixon AJ. Equine models of articular cartilage repair.. Cartilage 2011;2: 317–326.
    doi: 10.1177/1947603511406531pmc: PMC4297134pubmed: 26069590google scholar: lookup
  34. McCoy AM. Animal Models of Osteoarthritis: Comparisons and Key Considerations.. Vet Pathol 2015;52: 803–818.
    doi: 10.1177/0300985815588611pubmed: 26063173google scholar: lookup
  35. McIlwraith CW, Frisbie DD, Kawcak CE. The horse as a model of naturally occurring osteoarthritis.. Bone Jt Res 2012;1: 297–309.
    doi: 10.1302/2046-3758.111.2000132pmc: PMC3626203pubmed: 23610661google scholar: lookup
  36. Hurtig MB, Buschmann MD, Fortier LA, Hoemann CD, Hunziker EB, Jurvelin JS. Preclinical studies for cartilage repair: Recommendations from the international cartilage repair society.. Cartilage 2011;2: 137–152.
    doi: 10.1177/1947603511401905pmc: PMC4300779pubmed: 26069576google scholar: lookup
  37. McCoy AM. Animal Models of Osteoarthritis.. Vet Pathol 2015;52: 803–818.
    doi: 10.1177/0300985815588611pubmed: 26063173google scholar: lookup
  38. Kuyinu EL, Narayanan G, Nair LS, Laurencin CT. Animal models of osteoarthritis: Classification, update, and measurement of outcomes.. J Orthop Surg Res 2016;11: 19.
    doi: 10.1186/s13018-016-0346-5pmc: PMC4738796pubmed: 26837951google scholar: lookup
  39. Horohov DW. The equine immune responses to infectious and allergic disease: A model for humans?. Mol Immunol 2015;66: 89–96.
    doi: 10.1016/j.molimm.2014.09.020pubmed: 25457878google scholar: lookup
  40. Mair KH, Sedlak C, Käser T, Pasternak A, Levast B, Gerner W. The porcine innate immune system: An update.. Dev Comp Immunol 2014;45: 321–343.
    doi: 10.1016/j.dci.2014.03.022pmc: PMC7103209pubmed: 24709051google scholar: lookup
  41. Swindle MM, Makin A, Herron AJ, Clubb FJ, Frazier KS. Swine as Models in Biomedical Research and Toxicology Testing.. Vet Pathol 2012;49: 344–356.
    doi: 10.1177/0300985811402846pubmed: 21441112google scholar: lookup
  42. Gilbertie JM, Schnabel LV, Stefanovski D, Kelly DJ, Jacob ME, Schaer TP. Gram-negative multi-drug resistant bacteria influence survival to discharge for horses with septic synovial structures: 206 Cases (2010–2015).. Vet Microbiol 2018;226.
    doi: 10.1016/j.vetmic.2018.10.009pubmed: 30389045google scholar: lookup
  43. Ibberson CB, Parlet CP, Kwiecinski J, Crosby HA, Meyerholz DK, Horswill AR. Hyaluronan modulation impacts Staphylococcus aureus biofilm infection.. Infect Immun 2016;84: 1917–1929.
    doi: 10.1128/IAI.01418-15pmc: PMC4907140pubmed: 27068096google scholar: lookup
  44. Boles BR, Horswill AR. agr-mediated dispersal of Staphylococcus aureus biofilms.. PLoS Pathog 2008;4: e1000052.
    doi: 10.1371/journal.ppat.1000052pmc: PMC2329812pubmed: 18437240google scholar: lookup
  45. Wu H, Moser C, Wang H-ZZ, Høiby N, Song Z-JJ. Strategies for combating bacterial biofilm infections.. Int J Oral Sci 2015;7: 1–7.
    doi: 10.1038/ijos.2014.65pmc: PMC4817533pubmed: 25504208google scholar: lookup
  46. Fleming D, Rumbaugh K. The Consequences of Biofilm Dispersal on the Host.. Sci Rep 2018;8: 10738.
    doi: 10.1038/s41598-018-29121-2pmc: PMC6048044pubmed: 30013112google scholar: lookup
  47. Gries CM, Kielian T. Staphylococcal biofilms and immune polarization during prosthetic joint infection.. J Am Acad Orthop Surg 2017;25: S20–S24.
    doi: 10.5435/JAAOS-D-16-00636pmc: PMC5640443pubmed: 27922945google scholar: lookup
  48. Paharik AE, Horswill AR. The Staphylococcal Biofilm: Adhesins, Regulation, and Host Response.. Virulence Mechanisms of Bacterial Pathogens, Fifth Edition 2016. pp. 529–566.
    doi: 10.1128/microbiolspec.VMBF-0022-2015pmc: PMC4887152pubmed: 27227309google scholar: lookup
  49. Hanke ML, Kielian T. Deciphering mechanisms of staphylococcal biofilm evasion of host immunity.. Front Cell Infect Microbiol 2012;2: 62.
    doi: 10.3389/fcimb.2012.00062pmc: PMC3417388pubmed: 22919653google scholar: lookup
  50. Pinto N, Schumacher J, Taintor J, Degraves F, Duran S, Boothe D. Pharmacokinetics of amikacin in plasma and selected body fluids of healthy horses after a single intravenous dose.. 2010.
    doi: 10.1111/j.2042-3306.2010.00144.xpubmed: 21143642google scholar: lookup
  51. Nieto JE, Trela J, Stanley SD, Yamout S, Snyder JR. Pharmacokinetics of a combination of amikacin sulfate and penicillin G sodium for intravenous regional limb perfusion in adult horses.. Can J Vet Res 2016;80: 230–5.
    pmc: PMC4924558pubmed: 27408337
  52. Taintor J, Schumacher J, DeGraves F. Comparison of amikacin concentrations in normal and inflamed joints of horses following intra-articular administration.. Equine Vet J 2006;38: 189–91.
    pubmed: 16536391
  53. Murphey ED, Santschi EM, Papich MG. Regional intravenous perfusion of the distal limb of horses with amikacin sulfate.. J Vet Pharmacol Ther 1999;22: 68–71.
    pubmed: 10211721
  54. Walmsley EA, Anderson GA, Muurlink MA, Whitton RC. Retrospective investigation of prognostic indicators for adult horses with infection of a synovial structure.. Aust Vet J 2011;89: 226–231.
    doi: 10.1111/j.1751-0813.2011.00720.xpubmed: 21595644google scholar: lookup
  55. Taylor AH, Mair TS, Smith LJ, Perkins JD. Bacterial culture of septic synovial structures of horses: Does a positive bacterial culture influence prognosis?. Equine Vet J 2010;42: 213–218.
    doi: 10.2746/042516409X480403pubmed: 20486977google scholar: lookup
  56. Kirchner S, Fothergill JL, Wright EA, James CE, Mowat E, Winstanley C. Use of Artificial Sputum Medium to Test Antibiotic Efficacy Against <em>Pseudomonas aeruginosa</em> in Conditions More Relevant to the Cystic Fibrosis Lung.. J Vis Exp 2012; e3857.
    pmc: PMC3471314pubmed: 22711026doi: 10.3791/3857google scholar: lookup
  57. Haley CL, Colmer-Hamood JA, Hamood AN. Characterization of biofilm-like structures formed by Pseudomonas aeruginosa in a synthetic mucus medium.. BMC Microbiol 2012;12: 181.
    doi: 10.1186/1471-2180-12-181pmc: PMC3494610pubmed: 22900764google scholar: lookup
  58. Sønderholm M, Kragh KN, Koren K, Jakobsen TH, Darch SE, Alhede M. Pseudomonas aeruginosa aggregate formation in an alginate bead model system exhibits in vivo-like characteristics.. Appl Environ Microbiol 2017;83.
    doi: 10.1128/AEM.00113-17pmc: PMC5394317pubmed: 28258141google scholar: lookup
  59. Secor PR, Michaels LA, Ratjen A, Jennings LK, Singh PK. Entropically driven aggregation of bacteria by host polymers promotes antibiotic tolerance in Pseudomonas aeruginosa.. Proc Natl Acad Sci 2018;115: 10780–10785.
    doi: 10.1073/pnas.1806005115pmc: PMC6196481pubmed: 30275316google scholar: lookup
  60. Ceri H, Olson ME, Stremick C, Read RR, Morck D, Buret A. The Calgary Biofilm Device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms.. J Clin Microbiol 1999;37: 1771–6.
    pmc: PMC84946pubmed: 10325322
  61. Lorian V, Atkinson BA. Determination of the Range of Antibacterial Activity by Use of Viable Counts.. Journal of Clinical Microbiology 1982.
    pmc: PMC272296pubmed: 6809790
  62. Jensen LK, Bjarnsholt T, Kragh KN, Aalbæk B, Henriksen NL, Blirup SA. In Vivo Gentamicin Susceptibility Test for Prevention of Bacterial Biofilms in Bone Tissue and on Implants.. Antimicrob Agents Chemother 2019;63: e01889–18.
    doi: 10.1128/AAC.01889-18pmc: PMC6355599pubmed: 30455228google scholar: lookup
  63. Mottola C, Matias CS, Mendes JJ, Melo-Cristino J, Tavares L, Cavaco-Silva P. Susceptibility patterns of Staphylococcus aureus biofilms in diabetic foot infections.. BMC Microbiol 2016;16: 119.
    doi: 10.1186/s12866-016-0737-0pmc: PMC4918071pubmed: 27339028google scholar: lookup
  64. Bolt DM, Ishihara A, Weisbrode SE, Bertone AL. Effects of triamcinolone acetonide, sodium hyaluronate, amikacin sulfate, and mepivacaine hydrochloride, alone and in combination, on morphology and matrix composition of lipopolysaccharide-challenged and unchallenged equine articular cartilage explants.. Am J Vet Res 2008;69: 861–867.
    doi: 10.2460/ajvr.69.7.861pubmed: 18593234google scholar: lookup
  65. Gatell JM, San Miguel JG, Zamora L, Araujo V, Bonet M, Bohé M. Comparison of the nephrotoxicity and auditory toxicity of tobramycin and amikacin.. Antimicrob Agents Chemother 1983;23: 897–901.
    doi: 10.1128/aac.23.6.897pmc: PMC184998pubmed: 6614894google scholar: lookup
  66. Hengzhuang W, Wu H, Ciofu O, Song Z, Høiby N. Pharmacokinetics/Pharmacodynamics of Colistin and Imipenem on Mucoid and Nonmucoid Pseudomonas aeruginosa Biofilms.. Antimicrob Agents Chemother 2011;55: 4469–4474.
    doi: 10.1128/AAC.00126-11pmc: PMC3165294pubmed: 21670181google scholar: lookup
  67. Hengzhuang W, Wu H, Ciofu O, Song Z, Høiby N. In Vivo Pharmacokinetics/Pharmacodynamics of Colistin and Imipenem in Pseudomonas aeruginosa Biofilm Infection.. Antimicrob Agents Chemother 2012;56: 2683–2690.
    doi: 10.1128/AAC.06486-11pmc: PMC3346607pubmed: 22354300google scholar: lookup
  68. Belfield K, Bayston R, Birchall JP, Daniel M. Do orally administered antibiotics reach concentrations in the middle ear sufficient to eradicate planktonic and biofilm bacteria? A review.. Int J Pediatr Otorhinolaryngol 2015;79: 296–300.
    doi: 10.1016/j.ijporl.2015.01.003pubmed: 25623134google scholar: lookup
  69. Beenken KE, Dunman PM, McAleese F, Macapagal D, Murphy E, Projan SJ. Global gene expression in Staphylococcus aureus biofilms.. J Bacteriol 2004;186: 4665–4684.
    doi: 10.1128/JB.186.14.4665-4684.2004pmc: PMC438561pubmed: 15231800google scholar: lookup
  70. O’Gara JP. ica and beyond: Biofilm mechanisms and regulation in Staphylococcus epidermidis and Staphylococcus aureus.. FEMS Microbiol Lett 2007;270: 179–188.
    doi: 10.1111/j.1574-6968.2007.00688.xpubmed: 17419768google scholar: lookup
  71. Arciola CR, Campoccia D, Ravaioli S, Montanaro L. Polysaccharide intercellular adhesin in biofilm: structural and regulatory aspects.. Front Cell Infect Microbiol 2015;5: 7.
    doi: 10.3389/fcimb.2015.00007pmc: PMC4322838pubmed: 25713785google scholar: lookup
  72. Gawande PV, Leung KP, Madhyastha S. Antibiofilm and antimicrobial efficacy of Dispersinb®-KSL-w peptide-based wound gel against chronic wound infection associated bacteria.. Curr Microbiol 2014;68: 635–641.
    doi: 10.1007/s00284-014-0519-6pubmed: 24445333google scholar: lookup
  73. Crosby HA, Kwiecinski J, Horswill AR. Staphylococcus aureus Aggregation and Coagulation Mechanisms, and Their Function in Host–Pathogen Interactions.. Advances in Applied Microbiology 2016. pp. 1–41.
    doi: 10.1016/bs.aambs.2016.07.018pmc: PMC5221605pubmed: 27565579google scholar: lookup
  74. Josefsson E, Hartford O, O’Brien L, Patti JM, Foster T. Protection against Experimental Staphylococcus aureus Arthritis by Vaccination with Clumping Factor A, a Novel Virulence Determinant.. J Infect Dis 2001;184: 1572–1580.
    doi: 10.1086/324430pubmed: 11740733google scholar: lookup
  75. Matsuzaka S, Sato S, Miyauchi S. Estimation of joint fluid volume in the knee joint of rabbits by measuring the endogenous calcium concentration.. Clin Exp Rheumatol 20: 531–4.
    pubmed: 12175108
  76. Nakano T, Aherne FX, Thompson JR. Relative amounts of chondroitin sulfate and hyaluronic acid in synovial fluid from normal and osteochondrotic swine joints.. Canadian journal of comparative medicine October, 1984. pp. 434–6.
    pmc: PMC1236101pubmed: 6439398
  77. Van Pelt RW. Characteristics of normal equine tarsal synovial fluid.. Can J Comp Med Vet Sci 1967;31: 342–7.
    pmc: PMC1494768pubmed: 4229934
  78. Borg H, Carmalt JL. Postoperative Septic Arthritis After Elective Equine Arthroscopy Without Antimicrobial Prophylaxis.. Vet Surg 2013;42: 262–266.
    doi: 10.1111/j.1532-950X.2013.01106.xpubmed: 23432412google scholar: lookup
  79. Morton AJ. Diagnosis and treatment of septic arthritis.. Vet Clin North Am—Equine Pract 2005;21: 627–649.
    doi: 10.1016/j.cveq.2005.08.001pubmed: 16297725google scholar: lookup
  80. Gilbertie JM, Davis JL, Davidson GS, McDonald AM, Schirmer JM, Schnabel LV. Oral reserpine administration in horses results in low plasma concentrations that alter platelet biology.. Equine Vet J 2018; evj.13048.
    doi: 10.1111/evj.13048pubmed: 30465727google scholar: lookup
  81. Jarvis GE. Platelet Aggregation: Turbidimetric Measurements. Platelets and Megakaryocytes New Jersey: Humana Press; 2004. pp. 065–076.
    doi: 10.1385/1-59259-782-3:065pubmed: 15226534google scholar: lookup
  82. Zhou L, Schmaier AH. Platelet aggregation testing in platelet-rich plasma: description of procedures with the aim to develop standards in the field.. Am J Clin Pathol 2005;123: 172–83.
    doi: 10.1309/y9ec-63rw-3xg1-v313pubmed: 15842039google scholar: lookup

Citations

This article has been cited 38 times.
  1. De Bleeckere A, van Charante F, Debord T, Vandendriessche S, De Cock M, Verstraete M, Lamret F, Lories B, Boelens J, Reffuveille F, Steenackers HP, Coenye T. A novel synthetic synovial fluid model for investigating biofilm formation and antibiotic susceptibility in prosthetic joint infections. Microbiol Spectr 2025 Jan 7;13(1):e0198024.
    doi: 10.1128/spectrum.01980-24pubmed: 39612218google scholar: lookup
  2. Khatibzadeh SM, Dahlgren LA, Caswell CC, Ducker WA, Werre SR, Bogers SH. Equine bone marrow-derived mesenchymal stromal cells reduce established S. aureus and E. coli biofilm matrix in vitro. PLoS One 2024;19(10):e0312917.
    doi: 10.1371/journal.pone.0312917pubmed: 39480794google scholar: lookup
  3. Doub JB, Putnam N. Clinical Ramifications of Bacterial Aggregation in Pleural Fluid. Infect Dis Rep 2024 Jul 18;16(4):608-614.
    doi: 10.3390/idr16040046pubmed: 39051246google scholar: lookup
  4. Jin T. Exploring the role of bacterial virulence factors and host elements in septic arthritis: insights from animal models for innovative therapies. Front Microbiol 2024;15:1356982.
    doi: 10.3389/fmicb.2024.1356982pubmed: 38410388google scholar: lookup
  5. Cleaver L, Garnett JA. How to study biofilms: technological advancements in clinical biofilm research. Front Cell Infect Microbiol 2023;13:1335389.
    doi: 10.3389/fcimb.2023.1335389pubmed: 38156318google scholar: lookup
  6. Mutti M, Moreno DS, Restrepo-Córdoba M, Visram Z, Resch G, Corsini L. Phage activity against Staphylococcus aureus is impaired in plasma and synovial fluid. Sci Rep 2023 Oct 24;13(1):18204.
    doi: 10.1038/s41598-023-45405-8pubmed: 37875544google scholar: lookup
  7. Doub JB, Heil EL, Manson T. Adjuvant intra-articular vancomycin for recalcitrant Staphylococcal prosthetic joint infections of the knee. Eur J Orthop Surg Traumatol 2024 Feb;34(2):1031-1036.
    doi: 10.1007/s00590-023-03764-ypubmed: 37864658google scholar: lookup
  8. Coenye T. Biofilm antimicrobial susceptibility testing: where are we and where could we be going?. Clin Microbiol Rev 2023 Dec 20;36(4):e0002423.
    doi: 10.1128/cmr.00024-23pubmed: 37812003google scholar: lookup
  9. Taha M, Arnaud T, Lightly TJ, Peters D, Wang L, Chen W, Cook BWM, Theriault SS, Abdelbary H. Combining bacteriophage and vancomycin is efficacious against MRSA biofilm-like aggregates formed in synovial fluid. Front Med (Lausanne) 2023;10:1134912.
    doi: 10.3389/fmed.2023.1134912pubmed: 37359001google scholar: lookup
  10. Zhao N, Isguven S, Evans R, Schaer TP, Hickok NJ. Berberine disrupts staphylococcal proton motive force to cause potent anti-staphylococcal effects in vitro. Biofilm 2023 Dec;5:100117.
    doi: 10.1016/j.bioflm.2023.100117pubmed: 37090161google scholar: lookup
  11. Zhao N, Curry D, Evans RE, Isguven S, Freeman T, Eisenbrey JR, Forsberg F, Gilbertie JM, Boorman S, Hilliard R, Dastgheyb SS, Machado P, Stanczak M, Harwood M, Chen AF, Parvizi J, Shapiro IM, Hickok NJ, Schaer TP. Microbubble cavitation restores Staphylococcus aureus antibiotic susceptibility in vitro and in a septic arthritis model. Commun Biol 2023 Apr 17;6(1):425.
    doi: 10.1038/s42003-023-04752-ypubmed: 37069337google scholar: lookup
  12. Staats A, Burback PW, Casillas-Ituarte NN, Li D, Hostetler MR, Sullivan A, Horswill AR, Lower SK, Stoodley P. In Vitro Staphylococcal Aggregate Morphology and Protection from Antibiotics Are Dependent on Distinct Mechanisms Arising from Postsurgical Joint Components and Fluid Motion. J Bacteriol 2023 Apr 25;205(4):e0045122.
    doi: 10.1128/jb.00451-22pubmed: 36951588google scholar: lookup
  13. Drago L, Romanò D, Fidanza A, Giannetti A, Erasmo R, Mavrogenis AF, Romanò CL. Dithiotreitol pre-treatment of synovial fluid samples improves microbiological counts in peri-prosthetic joint infection. Int Orthop 2023 May;47(5):1147-1152.
    doi: 10.1007/s00264-023-05714-zpubmed: 36810966google scholar: lookup
  14. Pezzanite LM, Chow L, Phillips J, Griffenhagen GM, Moore AR, Schaer TP, Engiles JB, Werpy N, Gilbertie J, Schnabel LV, Antczak D, Miller D, Dow S, Goodrich LR. TLR-activated mesenchymal stromal cell therapy and antibiotics to treat multi-drug resistant Staphylococcal septic arthritis in an equine model. Ann Transl Med 2022 Nov;10(21):1157.
    doi: 10.21037/atm-22-1746pubmed: 36467344google scholar: lookup
  15. Leggett A, Li DW, Bruschweiler-Li L, Sullivan A, Stoodley P, Brüschweiler R. Differential metabolism between biofilm and suspended Pseudomonas aeruginosa cultures in bovine synovial fluid by 2D NMR-based metabolomics. Sci Rep 2022 Oct 15;12(1):17317.
    doi: 10.1038/s41598-022-22127-xpubmed: 36243882google scholar: lookup
  16. Su Y, Yrastorza JT, Matis M, Cusick J, Zhao S, Wang G, Xie J. Biofilms: Formation, Research Models, Potential Targets, and Methods for Prevention and Treatment. Adv Sci (Weinh) 2022 Oct;9(29):e2203291.
    doi: 10.1002/advs.202203291pubmed: 36031384google scholar: lookup
  17. Stamm J, Weißelberg S, Both A, Failla AV, Nordholt G, Büttner H, Linder S, Aepfelbacher M, Rohde H. Development of an artificial synovial fluid useful for studying Staphylococcus epidermidis joint infections. Front Cell Infect Microbiol 2022;12:948151.
    doi: 10.3389/fcimb.2022.948151pubmed: 35967857google scholar: lookup
  18. Sauer K, Stoodley P, Goeres DM, Hall-Stoodley L, Burmølle M, Stewart PS, Bjarnsholt T. The biofilm life cycle: expanding the conceptual model of biofilm formation. Nat Rev Microbiol 2022 Oct;20(10):608-620.
    doi: 10.1038/s41579-022-00767-0pubmed: 35922483google scholar: lookup
  19. Gilbertie JM, Schaer TP, Engiles JB, Seiler GS, Deddens BL, Schubert AG, Jacob ME, Stefanovski D, Ruthel G, Hickok NJ, Stowe DM, Frink A, Schnabel LV. A Platelet-Rich Plasma-Derived Biologic Clears Staphylococcus aureus Biofilms While Mitigating Cartilage Degeneration and Joint Inflammation in a Clinically Relevant Large Animal Infectious Arthritis Model. Front Cell Infect Microbiol 2022;12:895022.
    doi: 10.3389/fcimb.2022.895022pubmed: 35711655google scholar: lookup
  20. Shinde P, Stamatos N, Doub JB. Human Plasma Significantly Reduces Bacteriophage Infectivity Against Staphylococcus aureus Clinical Isolates. Cureus 2022 Apr;14(4):e23777.
    doi: 10.7759/cureus.23777pubmed: 35509731google scholar: lookup
  21. Rivera-Yoshida N, Bottagisio M, Attanasi D, Savadori P, De Vecchi E, Bidossi A, Franci A. Host Environment Shapes S. aureus Social Behavior as Revealed by Microscopy Pattern Formation and Dynamic Aggregation Analysis. Microorganisms 2022 Feb 28;10(3).
    doi: 10.3390/microorganisms10030526pubmed: 35336102google scholar: lookup
  22. Staats A, Burback PW, Schwieters A, Li D, Sullivan A, Horswill AR, Stoodley P. Rapid Aggregation of Staphylococcus aureus in Synovial Fluid Is Influenced by Synovial Fluid Concentration, Viscosity, and Fluid Dynamics, with Evidence of Polymer Bridging. mBio 2022 Apr 26;13(2):e0023622.
    doi: 10.1128/mbio.00236-22pubmed: 35254134google scholar: lookup
  23. Isguven S, Fitzgerald K, Delaney LJ, Harwood M, Schaer TP, Hickok NJ. In vitro investigations of Staphylococcus aureus biofilms in physiological fluids suggest that current antibiotic delivery systems may be limited. Eur Cell Mater 2022 Feb 2;43:6-21.
    doi: 10.22203/eCM.v043a03pubmed: 35106744google scholar: lookup
  24. Staats A, Li D, Sullivan AC, Stoodley P. Biofilm formation in periprosthetic joint infections. Ann Jt 2021 Oct;6.
    doi: 10.21037/aoj-20-85pubmed: 34859164google scholar: lookup
  25. Ivshina IB, Tyumina EA, Bazhutin GA, Vikhareva EV. Response of Rhodococcus cerastii IEGM 1278 to toxic effects of ibuprofen. PLoS One 2021;16(11):e0260032.
    doi: 10.1371/journal.pone.0260032pubmed: 34793540google scholar: lookup
  26. Staats A, Burback PW, Eltobgy M, Parker DM, Amer AO, Wozniak DJ, Wang SH, Stevenson KB, Urish KL, Stoodley P. Synovial Fluid-Induced Aggregation Occurs across Staphylococcus aureus Clinical Isolates and is Mechanistically Independent of Attached Biofilm Formation. Microbiol Spectr 2021 Oct 31;9(2):e0026721.
    doi: 10.1128/Spectrum.00267-21pubmed: 34523997google scholar: lookup
  27. Gordon J, Álvarez-Narváez S, Peroni JF. Antimicrobial Effects of Equine Platelet Lysate. Front Vet Sci 2021;8:703414.
    doi: 10.3389/fvets.2021.703414pubmed: 34490395google scholar: lookup
  28. Gupta TT, Gupta NK, Burback P, Stoodley P. Free-Floating Aggregate and Single-Cell-Initiated Biofilms of Staphylococcus aureus. Antibiotics (Basel) 2021 Jul 21;10(8).
    doi: 10.3390/antibiotics10080889pubmed: 34438938google scholar: lookup
  29. Steixner SJM, Spiegel C, Dammerer D, Wurm A, Nogler M, Coraça-Huber DC. Influence of Nutrient Media Compared to Human Synovial Fluid on the Antibiotic Susceptibility and Biofilm Gene Expression of Coagulase-Negative Staphylococci In Vitro. Antibiotics (Basel) 2021 Jun 29;10(7).
    doi: 10.3390/antibiotics10070790pubmed: 34209737google scholar: lookup
  30. Pezzanite L, Chow L, Hendrickson D, Gustafson DL, Russell Moore A, Stoneback J, Griffenhagen GM, Piquini G, Phillips J, Lunghofer P, Dow S, Goodrich LR. Evaluation of Intra-Articular Amikacin Administration in an Equine Non-inflammatory Joint Model to Identify Effective Bactericidal Concentrations While Minimizing Cytotoxicity. Front Vet Sci 2021;8:676774.
    doi: 10.3389/fvets.2021.676774pubmed: 34095281google scholar: lookup
  31. Knott S, Curry D, Zhao N, Metgud P, Dastgheyb SS, Purtill C, Harwood M, Chen AF, Schaer TP, Otto M, Hickok NJ. Staphylococcus aureus Floating Biofilm Formation and Phenotype in Synovial Fluid Depends on Albumin, Fibrinogen, and Hyaluronic Acid. Front Microbiol 2021;12:655873.
    doi: 10.3389/fmicb.2021.655873pubmed: 33995317google scholar: lookup
  32. Cai YM. Non-surface Attached Bacterial Aggregates: A Ubiquitous Third Lifestyle. Front Microbiol 2020;11:557035.
    doi: 10.3389/fmicb.2020.557035pubmed: 33343514google scholar: lookup
  33. Macias-Valcayo A, Staats A, Aguilera-Correa JJ, Brooks J, Gupta T, Dusane D, Stoodley P, Esteban J. Synovial Fluid Mediated Aggregation of Clinical Strains of Four Enterobacterial Species. Adv Exp Med Biol 2021;1323:81-90.
    doi: 10.1007/5584_2020_573pubmed: 32797406google scholar: lookup
  34. Bidossi A, Bottagisio M, Savadori P, De Vecchi E. Identification and Characterization of Planktonic Biofilm-Like Aggregates in Infected Synovial Fluids From Joint Infections. Front Microbiol 2020;11:1368.
    doi: 10.3389/fmicb.2020.01368pubmed: 32714301google scholar: lookup
  35. Domnin P, Arkhipova A, Petrov S, Sysolyatina E, Parfenov V, Karalkin P, Mukhachev A, Gusarov A, Moisenovich M, Khesuani Y, Ermolaeva S. An In Vitro Model of Nonattached Biofilm-Like Bacterial Aggregates Based on Magnetic Levitation. Appl Environ Microbiol 2020 Sep 1;86(18).
    doi: 10.1128/AEM.01074-20pubmed: 32680859google scholar: lookup
  36. Pestrak MJ, Gupta TT, Dusane DH, Guzior DV, Staats A, Harro J, Horswill AR, Stoodley P. Investigation of synovial fluid induced Staphylococcus aureus aggregate development and its impact on surface attachment and biofilm formation. PLoS One 2020;15(4):e0231791.
    doi: 10.1371/journal.pone.0231791pubmed: 32302361google scholar: lookup
  37. Saeed K, Sendi P, Arnold WV, Bauer TW, Coraça-Huber DC, Chen AF, Choe H, Daiss JL, Ghert M, Hickok NJ, Nishitani K, Springer BD, Stoodley P, Sculco TP, Brause BD, Parvizi J, McLaren AC, Schwarz EM. Bacterial toxins in musculoskeletal infections. J Orthop Res 2021 Feb;39(2):240-250.
    doi: 10.1002/jor.24683pubmed: 32255540google scholar: lookup
  38. Gilbertie JM, Schaer TP, Schubert AG, Jacob ME, Menegatti S, Ashton Lavoie R, Schnabel LV. Platelet-rich plasma lysate displays antibiofilm properties and restores antimicrobial activity against synovial fluid biofilms in vitro. J Orthop Res 2020 Jun;38(6):1365-1374.
    doi: 10.1002/jor.24584pubmed: 31922274google scholar: lookup
Subscribe to our newsletter
Join 99,727 horse owners like you who receive our email updates on horse health and nutrition.