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Journal of Medical Microbiology logo Journal of Medical Microbiology

Volume 74, Issue 7

A simple silicone elastomer colonization model highlights complexities of and interactions in biofilm formation Open Access

Abstract

Healthcare-associated infections (HAIs) significantly contribute to the burden of antimicrobial resistance. A major factor in HAIs is the colonization of indwelling medical devices by biofilm-forming opportunistic pathogens such as and . These organisms frequently co-infect, resulting in synergistic interactions with enhanced virulence and resistance to treatment.

and readily form dual-species biofilms on silicone elastomers, a commonly used medical device material, yet the colonization phenotypes of these organisms on such surfaces remain poorly understood.

We aimed to develop a simple, optically tractable model to mimic the colonization of indwelling medical devices to investigate and biofilm formation.

The system utilizes discs of a silicone elastomer embedded in agar, reflecting device-associated conditions and enabling high-resolution imaging of biofilms formed by and co-cultures.

Initial results using the silicone elastomer colonization model reveal robust biofilm formation. These biofilms exhibited morphological differences between dual-species biofilms formed by co-cultures with either yeast- or hyphal-form indicating the impact of differing cell morphotypes in biofilm-associated medical device colonization on silicone elastomers. Quantification of biofilm formation by crystal violet staining provided further validation of the system.

These findings underscore the importance of developing tools for biofilm study which more closely resemble the infectious microenvironment, with our work detailing such a system which can be employed in further study to improve strategies against device-related HAIs.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): antimicrobial resistance (AMR) , biofilm , biofilm-associated infections , Candida albicans , healthcare-associated infection (HAI) , interkingdom microbial communities and Staphylococcus aureus
Funding
This study was supported by the:
  • Microbiology Society
    • Principal Award Recipient: PaulA Hoskisson
  • Royal Academy of Engineering (Award RCSRF2021\11\15)
    • Principal Award Recipient: PaulA Hoskisson
  • Leverhulme Trust
    • Principal Award Recipient: LiamM Rooney
  • Leverhulme Trust
    • Principal Award Recipient: GailMcConnell
  • Biotechnology and Biological Sciences Research Council (Award BB/T011602/1)
    • Principal Award Recipient: GailMcConnell
  • Medical Research Council (Award MR/K015583/1)
    • Principal Award Recipient: GailMcConnell
  • Daphne Jackson Trust (Award n/a)
    • Principal Award Recipient: KatherineJ Baxter
  • Tenovus (Award S21-14)
    • Principal Award Recipient: KatherineJ Baxter
© 2025 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2025-12-12

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References

  1. Tomczyk S, Twyman A, de Kraker MEA, Coutinho Rehse AP, Tartari E et al. The first WHO global survey on infection prevention and control in health-care facilities. Lancet Infect Dis 2022; 22:845–856 [View Article] [PubMed]
     [Google Scholar]
  2. Morris AK, Russell CD. Enhanced surveillance of Staphylococcus aureus bacteraemia to identify targets for infection prevention. J Hosp Infect 2016; 93:169–174 [View Article] [PubMed]
     [Google Scholar]
  3. Pitiriga V, Kanellopoulos P, Bakalis I, Kampos E, Sagris I et al. Central venous catheter-related bloodstream infection and colonization: the impact of insertion site and distribution of multidrug-resistant pathogens. Antimicrob Resist Infect Control 2020; 9:189 [View Article] [PubMed]
     [Google Scholar]
  4. Suetens C, Latour K, Kärki T, Ricchizzi E, Kinross P et al. Prevalence of healthcare-associated infections, estimated incidence and composite antimicrobial resistance index in acute care hospitals and long-term care facilities: results from two european point prevalence surveys. Euro Surveill 2016; 23:1800516
     [Google Scholar]
  5. Isigi SS, Parsa AD, Alasqah I, Mahmud I, Kabir R. Predisposing factors of nosocomial infections in hospitalized patients in the United Kingdom: systematic review. JMIR Public Health Surveill 2023; 9:e43743 [View Article] [PubMed]
     [Google Scholar]
  6. Bouhrour N, Nibbering PH, Bendali F. Medical device-associated biofilm infections and multidrug-resistant pathogens. Pathogens 2024; 13:393 [View Article] [PubMed]
     [Google Scholar]
  7. Chkhaidze N, Imnadze P, Malania L, Chkhaidze I. Epidemiology and risk factors of nosocomial infection in hospitalized children and adults: a review. IJAMRS 2024; 4:516–521 [View Article]
     [Google Scholar]
  8. Stewart S, Robertson C, Pan J, Kennedy S, Dancer S et al. Epidemiology of healthcare-associated infection reported from a hospital-wide incidence study: considerations for infection prevention and control planning. J Hosp Infect 2021; 114:10–22 [View Article] [PubMed]
     [Google Scholar]
  9. Dadi NCT, Radochová B, Vargová J, Bujdáková H. Impact of healthcare-associated infections connected to medical devices – an update. Microorganisms 2021; 9:2332 [View Article] [PubMed]
     [Google Scholar]
  10. Mishra A, Aggarwal A, Khan F. Medical device-associated infections caused by biofilm-forming microbial pathogens and controlling strategies. Antibiotics 2024; 13:623 [View Article] [PubMed]
     [Google Scholar]
  11. Qu Y, McGiffin D, Kure C, Ozcelik B, Fraser J et al. Biofilm formation and migration on ventricular assist device drivelines. J Thorac Cardiovasc Surg 2020; 159:491–502 [View Article] [PubMed]
     [Google Scholar]
  12. Qu Y, Peleg AY, McGiffin D. Ventricular assist device-specific infections. J Clin Med 2021; 10:453 [View Article] [PubMed]
     [Google Scholar]
  13. Watson F, Swann M, Zimmer A, Chen R, Foulkes L et al. Chapter 7 - Aspects of biofilms on medical devices. In Das S. eds Understanding Microbial Biofilms Academic Press; 2023 pp 91–105 https://www.sciencedirect.com/science/article/pii/B978032399977900020X
     [Google Scholar]
  14. Yadav MK, Vidal JE, Song JJ. Chapter 2 - Microbial biofilms on medical indwelling devices. In Yadav MK, Singh BP. eds New and Future Developments in Microbial Biotechnology and Bioengineering: Microbial Biofilms Elsevier; 2020 pp 15–28 https://www.sciencedirect.com/science/article/pii/B9780444642790000025
     [Google Scholar]
  15. Sauer K, Stoodley P, Goeres DM, Hall-Stoodley L, Burmølle M et al. The biofilm life cycle: expanding the conceptual model of biofilm formation. Nat Rev Microbiol 2022; 20:608–620 [View Article] [PubMed]
     [Google Scholar]
  16. Horino T, Hori S. Metastatic infection during Staphylococcus aureus bacteremia. J Infect Chemother 2020; 26:162–169 [View Article] [PubMed]
     [Google Scholar]
  17. Mirzaei R, Sabokroo N, Ahmadyousefi Y, Motamedi H, Karampoor S. Immunometabolism in biofilm infection: lessons from cancer. Mol Med 2022; 28:10 [View Article] [PubMed]
     [Google Scholar]
  18. Khatoon Z, McTiernan CD, Suuronen EJ, Mah TF, Alarcon EI. Bacterial biofilm formation on implantable devices and approaches to its treatment and prevention. Heliyon 2018; 4:e01067 [View Article] [PubMed]
     [Google Scholar]
  19. Zhong L, Zhang S, Tang K, Zhou F, Zheng C et al. Clinical characteristics, risk factors and outcomes of mixed Candida albicans/bacterial bloodstream infections. BMC Infect Dis 2020; 20:810 [View Article] [PubMed]
     [Google Scholar]
  20. Tan JS, Joseph WS. Common fungal infections of the feet in patients with diabetes mellitus. Drugs Aging 2004; 21:101–112 [View Article] [PubMed]
     [Google Scholar]
  21. Vila T, Kong EF, Montelongo-Jauregui D, Van Dijck P, Shetty AC et al. Therapeutic implications of C. albicans-S. aureus mixed biofilm in a murine subcutaneous catheter model of polymicrobial infection. Virulence 2021; 12:835–851 [View Article] [PubMed]
     [Google Scholar]
  22. Arévalo-Jaimes BV, Torrents E. Candida albicans enhances Staphylococcus aureus virulence by progressive generation of new phenotypes. Curr Res Microb Sci 2024; 7:100316
     [Google Scholar]
  23. Paul S, Todd OA, Eichelberger KR, Tkaczyk C, Sellman BR et al. A fungal metabolic regulator underlies infectious synergism during Candida albicans-Staphylococcus aureus intra-abdominal co-infection. Nat Commun 2024; 15:5746 [View Article] [PubMed]
     [Google Scholar]
  24. Carolus H, Van Dyck K, Van Dijck P. Candida albicans and Staphylococcus species: a threatening twosome. Front Microbiol 2019; 10: [View Article] [PubMed]
     [Google Scholar]
  25. Todd OA, Peters BM. Candida albicans and Staphylococcus aureus pathogenicity and polymicrobial interactions: lessons beyond Koch’s postulates. J Fungi 2019; 5:81 [View Article]
     [Google Scholar]
  26. Victor A, Ribeiro J, F. Araújo F et al. Study of PDMS characterization and its applications in biomedicine: a review. J Mech Eng Biomech 2019; 4:1–9 [View Article]
     [Google Scholar]
  27. Held M, Kašpar O, Edwards C, Nicolau DV. Intracellular mechanisms of fungal space searching in microenvironments. Proc Natl Acad Sci USA 2019; 116:13543–13552 [View Article] [PubMed]
     [Google Scholar]
  28. McConnell G, Trägårdh J, Amor R, Dempster J, Reid E et al. A novel optical microscope for imaging large embryos and tissue volumes with sub-cellular resolution throughout. elife 2016; 5:e18659 [View Article] [PubMed]
     [Google Scholar]
  29. Rooney LM, Amos WB, Hoskisson PA, McConnell G. Intra-colony channels in E. coli function as a nutrient uptake system. ISME J 2020; 14:2461–2473 [View Article] [PubMed]
     [Google Scholar]
  30. Bottura B, Rooney LM, Hoskisson PA, McConnell G. Intra-colony channel morphology in Escherichia coli biofilms is governed by nutrient availability and substrate stiffness. Biofilm 2022; 4:100084 [View Article] [PubMed]
     [Google Scholar]
  31. Bottura B, Rooney L, Feeney M, Hoskisson PA, McConnell G. Quantifying the fractal complexity of nutrient transport channels in Escherichia coli biofilms under varying cell shape and growth environment. Microbiology 2024; 170:001511 [View Article] [PubMed]
     [Google Scholar]
  32. Bottura B, McConnell G, Florek LC, Smiley MK, Martin R et al. Oxygen microenvironments in E. coli biofilm nutrient transport channels: insights from complementary sensing approaches. bioRxiv 20242024.07.20.603676 [View Article] [PubMed]
     [Google Scholar]
  33. Baxter KJ, Sargison FA, Fitzgerald JR, McConnell G, Hoskisson PA. Time-lapse mesoscopy of Candida albicans and Staphylococcus aureus dual-species biofilms reveals a structural role for the hyphae of C. albicans in biofilm formation. Microbiology 2024; 170:001426 [View Article]
     [Google Scholar]
  34. Grossman AB, Burgin DJ, Rice KC. Quantification of Staphylococcus aureus biofilm formation by crystal violet and confocal microscopy. In Rice KC. eds Staphylococcus Aureus: Methods and Protocols New York, NY: Springer US; 2021 pp 69–78 https://doi.org/10.1007/978-1-0716-1550-8_9
     [Google Scholar]
  35. Hernandez-Cuellar E, Guerrero-Barrera AL, Avelar-Gonzalez FJ, Díaz JM, Santiago AS de et al. Characterization of Candida albicans and Staphylococcus aureus polymicrobial biofilm on different surfaces. Rev Iberoam Micol 2022; 39:36–43 [View Article] [PubMed]
     [Google Scholar]
  36. Schlecht LM, Peters BM, Krom BP, Freiberg JA, Hänsch GM et al. Systemic Staphylococcus aureus infection mediated by Candida albicans hyphal invasion of mucosal tissue. Microbiology 2015; 161:168–181 [View Article] [PubMed]
     [Google Scholar]
  37. van der Mei H, van de Belt-Gritter B, Dijk F, Busscher H. Initial biodeterioration of silicone rubber by c. albicans and c. tropicalis strains isolated from voice prostheses. Cells and Materials 1996; 6:157–163
     [Google Scholar]
  38. Barelle CJ, Manson CL, MacCallum DM, Odds FC, Gow NAR et al. GFP as a quantitative reporter of gene regulation in Candida albicans. Yeast 2004; 21:333–340 [View Article] [PubMed]
     [Google Scholar]
  39. Kong EF, Tsui C, Kucharíková S, Andes D, Van Dijck P et al. Commensal protection of Staphylococcus aureus against antimicrobials by Candida albicans biofilm matrix. mBio 2016; 7:01365–16 [View Article]
     [Google Scholar]
  40. Zago CE, Silva S, Sanitá PV, Barbugli PA, Dias CMI et al. Dynamics of biofilm formation and the interaction between Candida albicans and methicillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA). PLoS One 2015; 10:e0123206 [View Article] [PubMed]
     [Google Scholar]
  41. Gao Z, Song G, Zhang X, Li Q, Yang S et al. A facile PDMS coating approach to room-temperature gas sensors with high humidity resistance and long-term stability. Sens Actuators B Chem 2020; 325:128810 [View Article]
     [Google Scholar]
  42. Zainal M, Mohamad Zain N, Mohd Amin I, Ahmad VN. The antimicrobial and antibiofilm properties of allicin against Candida albicans and Staphylococcus aureus – a therapeutic potential for denture stomatitis. Saudi Dent J 2021; 33:105–111 [View Article] [PubMed]
     [Google Scholar]
  43. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M et al. Fiji: an open-source platform for biological-image analysis. Nat Methods 2012; 9:676–682 [View Article] [PubMed]
     [Google Scholar]
  44. Krause J, Geginat G, Tammer I. Prostaglandin E2 from Candida albicans stimulates the growth of Staphylococcus aureus in mixed biofilms. PLoS One 2015; 10:e0135404 [View Article] [PubMed]
     [Google Scholar]
  45. Liu D, Jiang P, Wang Y, Lu Y, Wu J et al. Engineering tridimensional hydrogel tissue and organ phantoms with tunable springiness. Adv Funct Materials 2023; 33: [View Article]
     [Google Scholar]
  46. Hoyer LL, Cota E. Candida albicans agglutinin-like sequence (als) family vignettes: a review of als protein structure and function. Front Microbiol 2016 [View Article] [PubMed]
     [Google Scholar]
  47. Jung P, Mischo CE, Gunaratnam G, Spengler C, Becker SL et al. Candida albicans adhesion to central venous catheters: impact of blood plasma-driven germ tube formation and pathogen-derived adhesins. Virulence 2020; 11:1453–1465 [View Article] [PubMed]
     [Google Scholar]
  48. Peters BM, Ovchinnikova ES, Krom BP, Schlecht LM, Zhou H et al. Staphylococcus aureus adherence to Candida albicans hyphae is mediated by the hyphal adhesin Als3p. Microbiology 2012; 158:2975–2986 [View Article] [PubMed]
     [Google Scholar]
  49. Alim D, Sircaik S, Panwar SL. The significance of lipids to biofilm formation in Candida albicans: an emerging perspective. J Fungi 2018; 4:140 [View Article]
     [Google Scholar]
  50. McCall AD, Pathirana RU, Prabhakar A, Cullen PJ, Edgerton M. Candida albicans biofilm development is governed by cooperative attachment and adhesion maintenance proteins. NPJ Biofilms Microbiomes 2019; 5:21 [View Article] [PubMed]
     [Google Scholar]
  51. Hoyer LL, Green CB, Oh SH, Zhao X. Discovering the secrets of the Candida albicans agglutinin-like sequence (ALS) gene family – a sticky pursuit. Med Mycol 2008; 46:1–15 [View Article] [PubMed]
     [Google Scholar]
  52. Jaśkiewicz M, Janczura A, Nowicka J, Kamysz W. Methods used for the eradication of staphylococcal biofilms. Antibiotics 2019; 8:174 [View Article] [PubMed]
     [Google Scholar]
  53. Berry KA, Verhoef MTA, Leonard AC, Cox G. Staphylococcus aureus adhesion to the host. Ann N Y Acad Sci 2022; 1515:75–96 [View Article] [PubMed]
     [Google Scholar]
  54. Bjarnsholt T, Whiteley M, Rumbaugh KP, Stewart PS, Jensen PØ et al. The importance of understanding the infectious microenvironment. Lancet Infect Dis 2022; 22:e88–e92 [View Article] [PubMed]
     [Google Scholar]
  55. Islayem M, Agha A, Al Bataineh MT, Bataineh MS, Alazzam A. Modification of surface topographies to inhibit candida biofilm formation. PLoS One 2024; 19:e0308705 [View Article] [PubMed]
     [Google Scholar]
  56. Al Bataineh MT, Alazzam A. Transforming medical device biofilm control with surface treatment using microfabrication techniques. PLoS One 2023; 18:e0292647 [View Article] [PubMed]
     [Google Scholar]
  57. Dardouri M, Bettencourt A, Martin V, Carvalho FA, Santos C et al. Using plasma-mediated covalent functionalization of rhamnolipids on polydimethylsiloxane towards the antimicrobial improvement of catheter surfaces. Biomater Adv 2022; 134:112563 [View Article] [PubMed]
     [Google Scholar]
  58. McShea L, Kambo HS, Maclean M, Sandison ME. Metal oxide-doped elastomeric materials for amplifying visible light-based antimicrobial activity. Mater Res Express 2022; 9:085402 [View Article]
     [Google Scholar]
  59. Galdiero E, Ricciardelli A, D’Angelo C, de Alteriis E, Maione A et al. Pentadecanoic acid against Candida albicans–Klebsiella pneumoniae biofilm: towards the development of an anti-biofilm coating to prevent polymicrobial infections. Res Microbiol 2021; 172:103880 [View Article] [PubMed]
     [Google Scholar]
  60. Groza A, Ciobanu CS, Popa CL, Iconaru SL, Chapon P et al. Structural properties and antifungal activity against Candida albicans biofilm of different composite layers based on Ag/Zn doped hydroxyapatite-polydimethylsiloxanes. Polymers 2016; 8:131 [View Article] [PubMed]
     [Google Scholar]
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A simple silicone elastomer colonization model highlights complexities of Candida albicans and Staphylococcus aureus interactions in biofilm formation
J. Med. Microbiol. 74, 002047 (2025); https://doi.org/10.1099/jmm.0.002047
/content/journal/jmm/10.1099/jmm.0.002047
/content/journal/jmm/10.1099/jmm.0.002047
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