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Observation of a Bone Invasion Model of Aspergillus fumigatus In Vitro and Analysis of the Antifungal Susceptibility

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Abstract

Background

Recently, the prevalence of invasive fungal infections has been on the rise, and one of the prevalent symptoms frequently observed is bone deterioration and bone loss.

Materials and Methods

Using an in vitro model we studied how Aspergillus fumigatus invades the bone. Pathological analysis was then employed to observe the structure and distinctive features of the invading fungal elements within the bone invasion model. Meanwhile, the antifungal effects of itraconazole, voriconazole, posaconazole, and amphotericin B were evaluated.

Results

The pathological findings showed that in the experimental group, fungal spores and hyphae invaded the bone tissue or were observed growing in the vicinity of the bone edge tissues, as indicated by both HE and PAS staining. In contrast, no fungal elements were observed in the control group, indicating that the in vitro bone invasion model of A. fumigatus was successfully constructed. Furthermore, the findings from the antifungal sensitivity test demonstrated that the lowest effective concentrations of antifungal drugs against the bone invasion model were as follows: 4 μg/ml for itraconazole, 0.5 μg/ml for voriconazole, 2 μg/ml for posaconazole, and 2 μg/ml for amphotericin B.

Discussion

The successful construction of the bone invasion model of A. fumigatus has provided a solid basis for future investigations into the mechanisms underlying A. fumigatus bone invasion and the study of its virulence factors. Utilizing bone models is of utmost importance in advancing the development of novel antifungal treatment approaches, as well as in effectively preventing and treating fungal bone invasion and osteolytic diseases.

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References

  1. Sousa C, Pasini RA, Pasqualotto A, et al. Imaging findings in aspergillosis: from head to toe. Mycopathologia. 2023;188(5):623–41.

    Article  PubMed  Google Scholar 

  2. Florez-Riaño AF, Ramírez-Sánchez IC. Breakthrough invasive sinusitis by Hormographiella aspergillata in a neutropenic patient receiving voriconazole therapy: a case report and review of breakthrough H. aspergillata infections. Mycopathologia. 2023;188(4):401–7.

    Article  PubMed  Google Scholar 

  3. Gamaletsou MN, Rammaert B, Bueno MA, et al. Aspergillus osteomyelitis: epidemiology, clinical manifestations, management, and outcome. J Infect. 2014;68(5):478–93.

    Article  PubMed  Google Scholar 

  4. Raz E, Win W, Hagiwara M, Lui YW, Cohen B, Fatterpekar GM. Fungal sinusitis. Neuroimaging Clin N Am. 2015;25(4):569–76.

    Article  PubMed  Google Scholar 

  5. Zhou W, et al. Managements and prognostic analyses in patients with invasive fungal rhinosinusitis. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2016;51(8):568–72.

    CAS  PubMed  Google Scholar 

  6. van de Veerdonk FL, Gresnigt MS, Romani L, Netea MG, Latgé JP. Aspergillus fumigatus morphology and dynamic host interactions. Nat Rev Microbiol. 2017;15(11):661–74.

    Article  PubMed  Google Scholar 

  7. Abad A, Fernández-Molina JV, Bikandi J, et al. What makes Aspergillus fumigatus a successful pathogen? Genes and molecules involved in invasive aspergillosis. Rev Iberoam Micol. 2010;27(4):155–82.

    Article  PubMed  Google Scholar 

  8. Miyabe S, Koizuka I, Ochi K, et al. Two cases of Aspergillus sinusitis with bone destruction. Auris Nasus Larynx. 2003;30(Suppl):S115–21.

    Article  PubMed  Google Scholar 

  9. Gabrielli E, Fothergill AW, Brescini L, et al. Osteomyelitis caused by Aspergillus species: a review of 310 reported cases. Clin Microbiol Infect. 2014;20(6):559–65.

    Article  CAS  PubMed  Google Scholar 

  10. Pagella F, Matti E, De Bernardi F, et al. Paranasal sinus fungus ball: diagnosis and management. Mycoses. 2007;50(6):451–6.

    Article  PubMed  Google Scholar 

  11. Leventakos K, Lewis RE, Kontoyiannis DP. Fungal infections in leukemia patients: how do we prevent and treat them? Clin Infect Dis. 2010;50(3):405–15.

    Article  PubMed  Google Scholar 

  12. Vallejo C, Barberán J. Empirical antifungal treatment: a valid alternative for invasive fungal infection. Rev Esp Quimioter. 2011;24(3):117–22.

    CAS  PubMed  Google Scholar 

  13. Lee DH, Yoon TM, Lee JK, Joo YE, Park KH, Lim SC. Invasive fungal sinusitis of the sphenoid sinus. Clin Exp Otorhinolaryngol. 2014;7(3):181–7.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Van Daele R, Spriet I, Wauters J, et al. Antifungal drugs: what brings the future? Med Mycol. 2019;57(Suppl_3):S328–43.

    Article  PubMed  Google Scholar 

  15. McGill TJ, Simpson G, Healy GB. Fulminant aspergillosis of the nose and paranasal sinuses: a new clinical entity. Laryngoscope. 2015;125(4):782.

    Article  PubMed  Google Scholar 

  16. Reddy CE, Gupta AK, Singh P, Mann SB. Imaging of granulomatous and chronic invasive fungal sinusitis: comparison with allergic fungal sinusitis. Otolaryngol Head Neck Surg. 2010;143(2):294–300.

    Article  PubMed  Google Scholar 

  17. Tortorano AM, Viviani MA, Biraghi E, et al. In vitro testing of fungicidal activity of biocides against Aspergillus fumigatus. J Med Microbiol. 2005;54(Pt 10):955–7.

    Article  CAS  PubMed  Google Scholar 

  18. Dijksterhuis J, Meijer M, van Doorn T, Samson R, Rico-Munoz E. Inactivation of stress-resistant ascospores of Eurotiales by industrial sanitizers. Int J Food Microbiol. 2018;285:27–33.

    Article  CAS  PubMed  Google Scholar 

  19. Reisberger EM, Abels C, Landthaler M, Szeimies RM. Histopathological diagnosis of onychomycosis by periodic acid–Schiff-stained nail clippings. Br J Dermatol. 2003;148(4):749–54.

    Article  PubMed  Google Scholar 

  20. Von Lilienfeld-Toal M, Wagener J, Einsele H, Cornely OA, Kurzai O. Invasive fungal infection. Dtsch Arztebl Int. 2019;116(16):271–8.

    Google Scholar 

  21. Chen MM, Shi GH, Dai Y, Fang WX, Wu Q. Identifying genetic variants associated with amphotericin B (AMB) resistance in Aspergillus fumigatus via k-mer-based GWAS. Front Genet. 2023;14:1133593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wang HC, Hsieh MI, Choi PC, Wu WL, Wu CJ. Species distribution and antifungal susceptibility of clinical Aspergillus isolates: a multicentre study in Taiwan, 2016–2020. Mycoses. 2023;66(8):711–22.

    Article  CAS  PubMed  Google Scholar 

  23. Pfaller MA, Carvalhaes CG, Castanheira M. Susceptibility patterns of amphotericin B, itraconazole, posaconazole, voriconazole and caspofungin for isolates causing invasive mould infections from the SENTRY antifungal surveillance program (2018–2021) and application of single-site epidemiological cutoff values to evaluate amphotericin B activity. Mycoses. 2023;66(10):854–68.

    Article  CAS  PubMed  Google Scholar 

  24. Fang W, Wu J, Cheng M, et al. Diagnosis of invasive fungal infections: challenges and recent developments. J Biomed Sci. 2023;30(1):42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Jenks JD, Seidel D, Cornely OA, et al. Voriconazole plus terbinafine combination antifungal therapy for invasive Lomentospora prolificans infections: analysis of 41 patients from the FungiScope® registry 2008–2019. Clin Microbiol Infect. 2020;26(6):784.e1-784.e5.

    Article  CAS  PubMed  Google Scholar 

  26. Earle K, Valero C, Conn DP, et al. Pathogenicity and virulence of Aspergillus fumigatus. Virulence. 2023;14(1):2172264.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Mowat E, Lang S, Williams C, McCulloch E, Jones B, Ramage G. Phase-dependent antifungal activity against Aspergillus fumigatus developing multicellular filamentous biofilms. J Antimicrob Chemother. 2008;62(6):1281–4.

    Article  CAS  PubMed  Google Scholar 

  28. Roilides E, Simitsopoulou M, Katragkou A, Walsh TJ. How biofilms evade host defenses. Microbiol Spectr. 2015. https://doi.org/10.1128/microbiolspec.mb-0012-2014.

    Article  PubMed  Google Scholar 

  29. Healy DY, Leid JG, Sanderson AR, Hunsaker DH. Biofilms with fungi in chronic rhinosinusitis. Otolaryngol Head Neck Surg. 2008;138(5):641–7.

    Article  PubMed  Google Scholar 

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Funding

This work was supported by the Key R&D Project of Hubei Province (Health Field) [2022BCE022], the Scientific Research Project of Hubei Provincial Commission of Health [WJ2021M261] and the Scientific research project of Jingzhou Science and Technology Bureau [2023HC43].

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Authors and Affiliations

Authors

Contributions

YS (Formal analysis, Visualization, Writing—original draft, Writing—review & editing), MS (Formal analysis, Visualization, Supervision, Specimen acquisition Writing—review & editing), DP (Specimen acquisition), WC (Specimen acquisition), CM (Specimen acquisition), HZ (Conceptualization, Data curation, Formal analysis), YS (Conceptualization, Funding acquisition, Project administration, Supervision, Validation, Writing—review & editing).

Corresponding author

Correspondence to Yi Sun.

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Conflict of interest

We declare no conflicts of interest.

Ethical Approval

The experiment adhered to the principles of Good Clinical Practice (GCP) and diligently complied with applicable laws and regulations.The clinical research was conducted in accordance with the approved research plan (Approval No. 2023-016-01) endorsed by the Ethics Committee of Jingzhou Hospital Affiliated to Yangtze University, with the primary aim of safeguarding the health and rights of the study participants.

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Handling Editor: Ferry Hagen.

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Shao, Y., Shen, M., Peng, D. et al. Observation of a Bone Invasion Model of Aspergillus fumigatus In Vitro and Analysis of the Antifungal Susceptibility. Mycopathologia 189, 4 (2024). https://doi.org/10.1007/s11046-023-00817-y

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