Clinical and pathological manifestations of Candida auris infections in mouse eyes
DOI:
https://doi.org/10.30539/zextra96Keywords:
Candida auris, histopathology, mice, ocular infectionAbstract
Background: Eye infections are one of the leading causes of vision loss, especially Background: The eye yeast infection is one of the leading causes of vision loss, especially in developing areas. Such infections may involve various body parts, either placed around the eye or inside the eye. Although ocular yeast infections are not as prevalent as bacterial infections, they are associated with more severe complications, particularly in immunocompromised individuals and those who overuse contact lenses. Fungal species, such as C. auris, can infect the eyes using a variety of virulence factors that depend on environmental and anatomical factors. The research was also designed to test the virulence and pathogenicity of the C. auris isolate through experimental induction of ocular infections in mice. Methodology: Mice were experimentally infected with a C. auris strain, PV715838.1. The concentration of 1 ×10^8 live yeast cells/ml was made by activating C. auris colonies in previous isolates and growing them on blood agar and BHI agar. Then, 30 BALB/c mice were used in the study, and they were divided into three groups that included a negative control group, a positive control group (received eye drops containing C. auris), and the dexamethasone-treated group before being infected. Three weeks later, the mice were euthanized, and their eye tissues were harvested and examined under histopathology, sectioned, and stained with hematoxylin and eosin. Results: The mice that were kept in the negative control group were healthy and did not present any signs of an ocular infection. Contrastingly, the infected population produced mild to moderate ocular lesions soon after inoculation, and this included conjunctival redness and mild corneal opacities. The immunosuppressed infected group presented with worse ocular lesions, which showed significant conjunctival hyperemia and dense corneal opacities, which developed to ulceration. These symptoms emerged faster and were more intense than those in the non-immunosuppressed infected group. Conclusion: This research proves that C. auris is able to induce ocular disease in mice, and the severity of the lesions is strongly associated with the immune status of the host.
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References
Abe, M., Kinjo, Y., Ueno, K., Takatsuka, S., Nakamura, S., Ogura, S., ... & Miyazaki, Y. (2018). Differences in ocular complications between Candida albicans and non-albicans Candida infection were analyzed using epidemiological studies and a mouse ocular candidiasis model. Frontiers in Microbiology, 9, 2477. https://doi.org/10.3389/fmicb.2018.02477
Al-Delemy, S. S. M. (2003). Immunologic and diagnostic study of Cryptococcosis (master’s thesis). College of Veterinary Medicine, University of Baghdad. (In Arabic).
Al-Hamedawi, T. M., Al-Timimi, I. H., & Al-Yasiri, E. A. (2012). Induction of parturition in Iraqi cows by using ergometrine, dexamethasone, and estrumate. The Iraqi Journal of Veterinary Medicine, 36(0E), 244–247. https://doi.org/10.30539/iraqijvm.v36i0E.423.
Aristimuno, B., Nirankari, V. S., Hemady, R. K., & Rodrigues, M. M. (1993). Spontaneous ulcerative keratitis in immunocompromised patients. American Journal of Ophthalmology, 115(2), 202–208. https://doi.org/10.1016/S0002-9394(14)73562-4
Breazzano, M. P., Tooley, A. A., Godfrey, K. J., Iacob, C. E., Yannuzzi, N. A., & Flynn, H. W. (2020). Candida auris and endogenous panophthalmitis: Clinical and histopathological features. American Journal of Ophthalmology Case Reports, 19, 100738. https://doi.org/10.1016/j.ajoc.2020.100738
Centers for Disease Control and Prevention. (2024, April 24). Clinical overview of Candida auris (C. auris). U.S. Department of Health & Human Services. Retrieved from https://www.cdc.gov/candida-auris/hcp/clinical-overview/index.html
Dire, O., Ahmad, A., Duze, S., & Patel, M. (2023). Survival of Candida auris on environmental surface materials and low-level resistance to disinfectant. Journal of Hospital Infection, 137, 17–23. https://doi.org/10.1016/j.jhin.2023.04.007
Du, H., Bing, J., Hu, T., Ennis, C. L., Nobile, C. J., & Huang, G. (2020). Candida auris: Epidemiology, biology, antifungal resistance, and virulence. PLoS Pathogens, 16(10), e1008921. https://doi.org/10.1371/journal.ppat.1008921
Egwuagu, C. E., Sun, L., Kim, S.-H., & Dambuza, I. M. (2015). Ocular inflammatory diseases: Molecular pathogenesis and immunotherapy. Current Molecular Medicine, 15(6), 517–528. https://doi.org/10.2174/1566524015666150731095426
Francois, L. M., Duncan, W., & Bernhard, H. (2013). Candida albicans pathogenicity mechanisms. Journal Name, 4(2), 119–128.
García-Bustos, V., Pemán, J., Ruiz-Gaitán, A., Cabañero-Navalón, M. D., Cabanilles-Boronat, A., Fernández-Calduch, M., Marcilla-Barreda, L., Sigona-Giangreco, I. A., Salavert, M., Tormo-Mas, M. Á., & Ruiz-Saurí, A. (2022). Host-pathogen interactions upon Candida auris infection: Fungal behaviour and immune response in Galleria mellonella. Emerging Microbes & Infections, 11(1), 136–146. https://doi.org/10.1080/22221751.2021.2017756.
Haseeb, A. A., Elhusseiny, A. M., Siddiqui, M. Z., Ahmad, K. T., & Sallam, A. B. (2021). Fungal endophthalmitis: A comprehensive review. Journal of Fungi, 7(11), 996. https://doi.org/10.3390/jof7110996
Hemady, R. K. (1995). Microbial keratitis in patients infected with the human immunodeficiency virus. Ophthalmology, 102(7), 1026–1030. https://doi.org/10.1016/S0161-6420(95)30916-9
Ibrahim, Z. I., Abdul-Mounam, M. A. W., & Alsufi, L. A. M. (2017). Study of ultrastructure changes in the liver of mice post-infection with Listeria monocytogenes. The Iraqi Journal of Veterinary Medicine, 41(1), 155–159.
Jafer, R. S., & Kassab, H. J. (2025). Development and characterization of lornoxicam-infused ocular gel for effective treatment of ocular inflammation in domestic cats. Iraqi Journal of Veterinary Medicine, 49(1), 8–15. https://doi.org/10.30539/pw6vsy73
Jarullah, M. A. (2022). Molecular and pathological detection of Candida albicans isolates from children, small animals, and pet birds (Master’s thesis)—University of Baghdad, College of Veterinary Medicine, Department of Veterinary Public Health.
Kalkanci, A., & Ozdek, S. (2011). Ocular fungal infections. Current Eye Research, 36(3), 179–189. https://doi.org/10.3109/02713683.2010.530751
Kareem, A. A., Aziz, T. A., Ahmed, Z. A., Othman, H. H., & Hussain, S. A. (2022). Anti-inflammatory activity of Gingko biloba extract in cotton pellet-induced granuloma in rats: A comparative study with prednisolone and dexamethasone. Iraqi Journal of Pharmaceutical Sciences, 31(1), 184–193. https://doi.org/10.31351/vol31iss1pp184-193
Kathuria, S., Singh, P. K., Sharma, C., Prakash, A., Masih, A., Kumar, A., Meis, J. F., & Chowdhary, A. (2015). Multidrug-resistant Candida auris misidentified as Candida haemulonii: Characterization by matrix-assisted laser desorption ionization–time of flight mass spectrometry and DNA sequencing and its antifungal susceptibility profile variability by Vitek 2, CLSI broth microdilution, and Etest method. Journal of Clinical Microbiology, 53(6), 1823–1830. https://doi.org/10.1128/JCM.00367-15
Khan, Z., Ahmad, S., Al-Sweih, N., Joseph, L., Alfouzan, W., & Asadzadeh, M. (2018). Increasing prevalence, molecular characterization, and antifungal drug susceptibility of serial Candida auris isolates in Kuwait. PLoS ONE, 13(4), e0195743. https://doi.org/10.1371/journal.pone.0195743
Linek, J. (2004). Mycotic endophthalmitis in a dog caused by Candida albicans. Veterinary Ophthalmology, 7(3), 159–162. https://doi.org/10.1111/j.1463-5224.2004.04022.x
Luna, L. G. (1968). Manual of histological staining methods. The Armed Forces Institute of Pathology.
Maniatopoulos, C., Rodriguez, A., Deporter, D. A., & Melcher, A. H. (1986). An improved method for preparing histological sections of metallic implants. International Journal of Oral and Maxillofacial Implants, 1(1), 31–37.
Phongkhun, K., Pothikamjorn, T., Srisurapanont, K., Manothummetha, K., Sanguankeo, A., Thongkam, A., ... & Permpalung, N. (2023). Prevalence of ocular candidiasis and Candida endophthalmitis in patients with candidemia: A systematic review and meta-analysis. Clinical Infectious Diseases, 76(10), 1738–1749. https://doi.org/10.1093/cid/ciad064
Pradeep, T., Mehra, D., & Le, P. H. (2023, May 1). Histology, eye. In StatPearls. StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK544343/
Ranjith, K., Sontam, B., Sharma, S., Joseph, J., Chathoth, K. N., Sama, K. C., ... & Shivaji, S. (2017). Candida species from eye infections: Drug susceptibility, virulence factors, and molecular characterization. Investigative Ophthalmology & Visual Science, 58(10), 4201–4209. https://doi.org/10.1167/iovs.17-21677
Rasheed, K. N., Mezher, M. A., & Thamer, I. K. (2020). Microscopic vision of an experimental infection effect with Candida glabrata yeast in the histological structure of the heart and lungs in immunosuppressed male mice and other normal mice. Indian Journal of Public Health Research & Development, 11(2), 2317–2321.
Saddam, A. C. (2021). Effect of chicory (Cichorium intybus L.) leaves extract on protecting certain liver enzymes in mice against carbon tetrachloride-induced hepatotoxicity. Iraqi Journal of Agricultural Sciences, 52(5), 1248–1253.
Salman, A. Y., & Faraj, M. K. (2015). Effect of hydroalcoholic leaves extract of Datura stramonium on pathogenic Candida albicans. The Iraqi Journal of Veterinary Medicine, 39(2), 55–61.
Santana, D. J., Anku, J. A. E., Zhao, G., Zarnowski, R., Johnson, C. J., Hautau, H., Visser, N. D., Ibrahim, A. S., Andes, D., Nett, J. E., Singh, S., & O’Meara, T. R. (2023). A Candida auris–specific adhesin, Scf1, governs surface association, colonization, and virulence. Mycoses. Advance online publication. https://doi.org/10.1126/science.adf8972
Satala, D., Juszczak, M., Wronowska, E., Surowiec, M., Kulig, K., Kozik, A., ... & Karkowska-Kuleta, J. (2022). Similarities and differences among species closely related to Candida albicans: C. tropicalis, C. dubliniensis, and C. auris. Cellular Microbiology, 2022(1), 2599136. https://doi.org/10.1155/2022/2599136
Saud, M. D., & Ghani, S. M. (2006). Phosphodiester conjugation of metronidazole and dexamethasone as a possible mutual prodrug. Iraqi Journal of Pharmaceutical Sciences, 15(1), 68–80.
Sharma, C., & Kadosh, D. (2023). Perspective on the origin, resistance, and spread of the emerging human fungal pathogen Candida auris. PLoS Pathogens, 19(3), e1011190. https://doi.org/10.1371/journal.ppat.1011190.
Shenoy, V., Ballenberger, M., Prince, A., & Maslak, S. (2019). Panophthalmitis from Candida auris. Annals of Internal Medicine, 171(12), 941–943. https://doi.org/10.7326/L19-0323.
Slowik, M., Biernat, M. M., Urbaniak-Kujda, D., Kapelko-Slowik, K., & Misiuk-Hojlo, M. (2015). Mycotic infections of the eye. Advances in Clinical and Experimental Medicine, 24(6), 1113–1117. https://doi.org/10.17219/acem/60402.
Sodhi, G., Liu, E., Renz, J., Heher, K., & Kapadia, M. (2016). Infections of the eyelids, orbit, and ocular adnexa. In N. Laver & C. Specht (Eds.), The infected eye (pp. 191–208). Springer. https://doi.org/10.1007/978-3-319-22198-0_12
Taghi, H. S., Jabar, E. G., & Almajidi, Y. Q. (2024). Formulation, in-vitro evaluation, and animal study of levofloxacin/tinidazole-loaded pH-dependent in-situ gel for ophthalmic drug delivery. Iraqi Journal of Veterinary Medicine, 48(2), 89–97. https://doi.org/10.30539/0tg7mb26
Thomas, P. A., & Kaliamurthy, J. (2013). Mycotic keratitis: Epidemiology, diagnosis and management. Clinical Microbiology and Infection, 19(3), 210–220. https://doi.org/10.1111/1469-0691.12126
Widanage, M. C. D., Singh, K., Li, J., Yarava, J. R., Scott, F. J., Xu, Y., ... & Wang, T. (2024). Unveiling cell wall structure and echinocandin response in Candida auris and Candida albicans via solid-state NMR. bioRxiv. https://doi.org/10.1101/2024.12
Wu, T. G., Wilhelmus, K. R., & Mitchell, B. M. (2002). Experimental keratomycosis in immunosuppressed mice. Investigative Ophthalmology & Visual Science, 43(13), 1613.
Yassein, S. N., Khalil, L. W., & Khalaf, J. M. (2017). Detection of mycotic caprine mastitis through studying the oxidant/antioxidant state. Iraqi Journal of Veterinary Sciences, 31(2), 45–52.
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