A case of corneal infection with Clonostachys rosea

A case of corneal infection with Clonostachys rosea | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A case of corneal infection with Clonostachys rosea Xiaona Liu, Juanjuan Zheng, Zihan Huo, Feng Wu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4877880/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Apr, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted 12 You are reading this latest preprint version Abstract Background: There have been no reported cases of infectious diseases associated with Clonostachys rosea . Case presentation: The patient, 53 years old, was admitted with complaints of "foreign body sensation, tearing, and pain in the left eye for 2 weeks, aggravated for 7 days." And was admitted with a diagnosis of "fungal keratitis (left)." Fungal growth was confirmed through corneal scrape culture. Antifungal treatment included natamycin and fluconazole eye drops, along with oral terbinafine tablets. Levofloxacin eye drops were administered to prevent bacterial infection, and praprofen eye drops were prescribed to alleviate anterior chamber reaction. After 4 days of treatment, the patient reported reduced foreign body sensation, tearing, and pain in the left eye. Follow-up visits were scheduled at regular intervals, during which medication remained consistent and dosage gradually decreased with symptom improvement. After 35 days, ulcer lesions had formed scars, and confocal examination of the corneal focal area revealed normal epithelial cell growth with scar-like reflection below, without obvious mycelial hyperrefraction. Conclusions: Herein, we describe a case of corneal infection attributed to Clonostachys rosea . We outline the development and treatment of this infection to enhance clinical comprehension and management of similar cases. Clonostachys rosea Keratitis Fungus Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Currently, fungal keratitis poses a significant threat to vision [ 1 ] , with Fusarium, Aspergillus, and Candida being the most prevalent strains [ 2 ] . Fungal keratitis is associated with extended healing times and a five-fold increase in corneal perforations, making it a more severe condition. As of now, no cases of corneal infection attributed to Clonostachys rosea have been reported. Case Report The patient, a middle-aged male, was admitted with complaints of "foreign body sensation, tearing, and pain in the left eye for 2 weeks, aggravated for 7 days." These symptoms arose following the loss of the left eye two weeks ago, which went untreated and worsened over the past week. Initially diagnosed with "conjunctivitis" at a local hospital, the patient received chondroitin sulfate eye drops, ganciclovir gel, compound toricamide eye drops, compound Xueshuantong dropping pills, and Longze Xiongdan capsules for oral treatment, but observed no improvement. Seeking further treatment, the patient presented to our hospital and was admitted with a diagnosis of "fungal keratitis (left)." Eye examination revealed a visual acuity of 0.6 in both eyes, intraocular pressures of 19mmHg in the right eye and 8mmHg in the left eye, and congestive conjunctiva in the left eye. The right cornea appeared clear, while the left cornea exhibited a 3mm diameter ulcer below the temporal part, with attached surface fur (see Fig. 1 ). The anterior chamber of the right eye displayed moderate clarity with clear aqueous humor, while the left eye exhibited moderate clarity with cloudy aqueous humor. Confocal microscopy revealed abundant myceliform hyperrefraction in the corneal ulcer area of the left eye (see Fig. 2 ), with blurred scanning observed below. The more transparent region at the lesion's edge was scanned to approximately 200µm, revealing concealed mycel-like hyperrefraction with blurred scanning underneath, along with increased inflammatory cells in the stromal layer and blurred cells in the inner cortex. Corneal scrape examination revealed branch-separated mycelium under calcium fluorescence white staining microscopy (see Fig. 3 ). Antifungal treatment included natamycin and fluconazole eye drops, along with oral terbinafine tablets. Levofloxacin eye drops were administered to prevent bacterial infection, and praprofen eye drops were prescribed to alleviate anterior chamber reaction. Fungal growth was confirmed through corneal scrape culture (see Fig. 4 ), with penicillium suspected and subsequently identified through sequencing. After 4 days of treatment, the patient reported reduced foreign body sensation, tearing, and pain in the left eye. Ophthalmic examination showed improved visual acuity (0.6) and decreased intraocular pressure, with reduced congestion and peripheral infiltration in the cornea. Partial repair of the peripheral corneal epithelium was observed, leading to the patient's discharge. Discharge instructions included specific eye drop regimens and oral terbinafine hydrochloride tablets. Follow-up visits were scheduled at regular intervals, during which medication remained consistent and dosage gradually decreased with symptom improvement. One month later, sequencing results confirmed Clonostachys rosea (GenBank No. MN889471.1, 100% similarity). After 35 days, ulcer lesions had formed scars (see Fig. 5 ), and confocal examination of the corneal focal area revealed normal epithelial cell growth with scar-like reflection below, without obvious mycelial hyperrefraction (see Fig. 6 ). Discussion Corneal ulcers rank second only to cataracts as a leading cause of blindness in developing countries. Fungal keratitis is increasingly recognized as a significant threat to vision [ 1 ] , with Fusarium, Aspergillus, and Candida being the most prevalent causative strains [ 2 ] . Clonostachys rosea , a filamentous fungus widely found in soil, belongs to the genus Cloradium within the Rubiophoraceae family. It has diverse applications in biological control, fermentation, degradation, and bioenergy [ 3 – 8 ] . Additionally, it promotes plant growth [ 4 , 9 , 10 ] . Its mechanisms of action include nutrient competition, hyperparasitism, synthesis of antibacterial substances, and induction of plant disease resistance. On PDA medium at 25°C, the colony of Clonostachys rosea appears white and light orange under fluorescent light. It produces white or light yellow multi-branched septate mycelium, bicyclic or similar primary conidia, penicilliform secondary conidia, and slightly curved distal wide round conidia [ 8 , 11 ] . Under specific conditions, chlamydospores can be produced, which exhibit enhanced stress resistance compared to conidia [ 12 ] . The ocular symptoms observed in the patient infected with Clonostachys rosea resembled those commonly seen in filamentous fungal infections, characterized by a 3mm diameter ulcer with moss adhering to the surface. The growth of the corneal scrape culture was rapid, with the appearance of a white colony after 2 days, followed by a transition to yellowish coloration after 6 days. Lactil cotton blue staining revealed branch-separated mycelium, sporulation resembling bottle stems, solitary or penicilliform-like broom structures, and pseudocephalic growth of conidia. Clinical treatment with natamycin eye drops, fluconazole eye drops, and oral terbinafine tablets yielded satisfactory results, leading to scar tissue formation within a month. Conclusions As of now, no infectious diseases linked to Clonostachys rosea have been reported. This case summary aims to contribute to the knowledge and experience in clinical diagnosis and treatment of similar infections. Declarations Ethical Approval and Consent to participate “Not applicable” in this section. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Availability of supporting data “Not applicable” in this section. Competing interests "The authors declare that they have no competing interests" in this section. Funding “Not applicable” in this section. Authors' contributions Xiaona Liu was the major contributor in writing the manuscript. Juanjuan Zheng, Zihan Huo and Feng Wu analyzed and interpreted the result regarding the disease . All authors read and approved the final manuscript. Acknowledgements “Not applicable” in this section. References Priyadarshini SR, Soni T, Sahu SK, et al. Acremonium keratitis: Risk factors, clinical characteristics, management, and outcome in 65 cases. Indian J Ophthalmol. 2022. 70(10): 3522-3527. Garg P, Roy A, Roy S. Update on fungal keratitis. Curr Opin Ophthalmol. 2016. 27(4): 333-9. Biology and applications of Clonostachys rosea . JOURNAL OF APPLIED MICROBIOLOGY. 2020. 129(3): 486-495. MENG F, LV R, CHENG M, al e. Insights into the molecular basis of biocontrol of Botrytis cinerea by Clonostachys rosea in tomato. SCIENTIA HORTICULTURAE. 2022. 291. Han Z, Ghanizadeh H, Zhang H, et al. Clonostachys rosea Promotes Root Growth in Tomato by Secreting Auxin Produced through the Tryptamine Pathway. J Fungi (Basel). 2022. 8(11). Mascarin GM, da Silva A, da Silva TP, Kobori NN, Morandi M, Bettiol W. Clonostachys rosea : Production by Submerged Culture and Bioactivity Against Sclerotinia sclerotiorum and Bemisia tabaci. Front Microbiol. 2022. 13: 851000. Ntsobi N, Fanadzo M, Le Roes-Hill M, Nchu F. Effects of Clonostachys rosea f. catenula Inoculum on the Composting of Cabbage Wastes and the Endophytic Activities of the Composted Material on Tomatoes and Red Spider Mite Infestation. Microorganisms. 2021. 9(6). Venkatesan RM, Muthusamy K, Iruthayasamy J, et al. First Report of Clonostachys rosea as a Mycoparasite on Sclerotinia sclerotiorum Causing Head Rot of Cabbage in India. Plants (Basel). 2023. 12(1). RAVNSKOV SABINE JB, KNUDSEN INGE MB ea. Soil inoculation with the biocontrol agent Clonostachys rosea and the mycorrhizal fungus Glomus intraradices results in mutual inhibition, plant growth promotion and alteration of soil microbial communities. SOIL BIOLOGY & BIOCHEMISTRY. 2006. 38(12): 3453-3462. Corrêa lB, Bettiol W, Morandi MAB. Biological control of Pythium aphanidermatum root rot and growth promotion of hydroponic lettuce by Clonostachys rosea . Sociedade Brasileira de Fitopatologia. 2010. (4). Goh YK, Marzuki NF, Tuan Pa T, et al. Biocontrol and Plant-Growth-Promoting Traits of Talaromyces apiculatus and Clonostachys rosea Consortium against Ganoderma Basal Stem Rot Disease of Oil Palm. Microorganisms. 2020. 8(8). 王琦, 冯静红, 孙占斌等. 氧化胁迫对粉红螺旋聚孢霉生长和产厚垣孢子的影响. 生物技术通报. 2018. 34(4): 6. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 16 Apr, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Revision requested 27 Dec, 2024 Reviews received at journal 12 Dec, 2024 Reviewers agreed at journal 03 Dec, 2024 Reviews received at journal 03 Dec, 2024 Reviewers agreed at journal 27 Nov, 2024 Reviews received at journal 24 Nov, 2024 Reviewers agreed at journal 24 Nov, 2024 Reviewers invited by journal 18 Nov, 2024 Editor invited by journal 09 Aug, 2024 Editor assigned by journal 08 Aug, 2024 Submission checks completed at journal 08 Aug, 2024 First submitted to journal 07 Aug, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4877880","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":347857483,"identity":"dc74b2b6-b825-4b36-b82d-40867a2c1048","order_by":0,"name":"Xiaona Liu","email":"","orcid":"","institution":"Jinan Mingshui Eye Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiaona","middleName":"","lastName":"Liu","suffix":""},{"id":347857484,"identity":"0266bc2d-dad5-400a-8f87-79397a48a6eb","order_by":1,"name":"Juanjuan Zheng","email":"","orcid":"","institution":"Jinan Mingshui Eye Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Juanjuan","middleName":"","lastName":"Zheng","suffix":""},{"id":347857485,"identity":"95750587-fa66-45ce-b43c-2a31491f87e5","order_by":2,"name":"Zihan Huo","email":"","orcid":"","institution":"Jinan Mingshui Eye Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zihan","middleName":"","lastName":"Huo","suffix":""},{"id":347857486,"identity":"aa4d990e-c75c-4c0b-abd8-fc7a346062ed","order_by":3,"name":"Feng Wu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzklEQVRIiWNgGAWjYBAC++MN6T8+8NjYMbY3EKvnzIEHkjNk0pKZew4Qq+VG4gNpHpvDjO0zEojUwdiQnGA4I4eZmXfm4403GGpsoglqYWY4lpDw4Qwbn+TstGILhmNpuQ2EtLAx9iQcnNnDw2w4O8dMgrHhMGEtPMz8H5t5/0kw7r95hkgtEmwMycw8PAaMjTN4iNRiwMOQxjiDJyGZsQfolwRi/GIg/yCN4QPPf2BUHt5440ONDWEtKNolEkhRDtFCqo5RMApGwSgYGQAAMrpAQG4dSwEAAAAASUVORK5CYII=","orcid":"","institution":"Jinan Mingshui Eye Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Feng","middleName":"","lastName":"Wu","suffix":""}],"badges":[],"createdAt":"2024-08-08 03:46:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4877880/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4877880/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-025-10903-9","type":"published","date":"2025-04-16T15:57:26+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":64712306,"identity":"29900eed-dbe0-4bb9-b3ae-8c2e6e93fd7c","added_by":"auto","created_at":"2024-09-18 02:04:37","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":521230,"visible":true,"origin":"","legend":"\u003cp\u003eA 3mm diameter ulcer is visible below the temporal part of the left eye, with attached surface fur.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4877880/v1/f540b9f0ce7a41fc37606650.jpeg"},{"id":64712303,"identity":"f035af4c-2aaf-4da0-8adc-7289c45a5856","added_by":"auto","created_at":"2024-09-18 02:04:37","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":32710,"visible":true,"origin":"","legend":"\u003cp\u003eConfocal microscopy revealed abundant myceliform hyperrefraction in the corneal ulcer area of the left eye.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4877880/v1/c5ef2fd2d2a76172f6e43e2a.jpeg"},{"id":64713306,"identity":"c1189905-7b29-41fc-81e5-41ba45c5a9d1","added_by":"auto","created_at":"2024-09-18 02:12:37","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":514760,"visible":true,"origin":"","legend":"\u003cp\u003eBranch-separated mycelium is visible under calcium fluorescence white staining microscopy.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4877880/v1/1a532fcffde2863ec04e6266.jpeg"},{"id":64712301,"identity":"49a5141c-5230-4219-ad3e-4d2fb076243d","added_by":"auto","created_at":"2024-09-18 02:04:37","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1121061,"visible":true,"origin":"","legend":"\u003cp\u003eCorneal scrape culture displayed fungal growth, confirmed by lactic acid phenol cotton blue staining and fluorescent staining (×1000). Sequencing identified \u003cem\u003eClonostachys rosea\u003c/em\u003e.\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4877880/v1/37723cc533301eedd452db4b.jpeg"},{"id":64712304,"identity":"31f87cc3-63f3-45c8-b849-ecb03846dcf0","added_by":"auto","created_at":"2024-09-18 02:04:37","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":527881,"visible":true,"origin":"","legend":"\u003cp\u003eAfter 35 days, ulcer lesions developed into scars.\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4877880/v1/d6da583ec2d4e2b18700d87a.jpeg"},{"id":64713307,"identity":"8e61f0fa-20f3-4e86-994e-b89315dcc0c1","added_by":"auto","created_at":"2024-09-18 02:12:37","extension":"jpeg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":30818,"visible":true,"origin":"","legend":"\u003cp\u003eConfocal examination of the corneal focal area of the left eye showed the growth of normal epithelial cells with scar-like reflection below. No obvious mycelial hyperrefraction was observed.\u003c/p\u003e","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4877880/v1/130df25c62a64f76be96fb09.jpeg"},{"id":81050968,"identity":"f80c85ea-e913-4c9c-a996-8742a83b2a52","added_by":"auto","created_at":"2025-04-21 16:09:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3102126,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4877880/v1/a18c7f85-3c9e-4476-b1d6-526fa5c78c08.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A case of corneal infection with Clonostachys rosea","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCurrently, fungal keratitis poses a significant threat to vision\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e, with Fusarium, Aspergillus, and Candida being the most prevalent strains\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Fungal keratitis is associated with extended healing times and a five-fold increase in corneal perforations, making it a more severe condition. As of now, no cases of corneal infection attributed to \u003cem\u003eClonostachys rosea\u003c/em\u003e have been reported.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eThe patient, a middle-aged male, was admitted with complaints of \"foreign body sensation, tearing, and pain in the left eye for 2 weeks, aggravated for 7 days.\" These symptoms arose following the loss of the left eye two weeks ago, which went untreated and worsened over the past week. Initially diagnosed with \"conjunctivitis\" at a local hospital, the patient received chondroitin sulfate eye drops, ganciclovir gel, compound toricamide eye drops, compound Xueshuantong dropping pills, and Longze Xiongdan capsules for oral treatment, but observed no improvement. Seeking further treatment, the patient presented to our hospital and was admitted with a diagnosis of \"fungal keratitis (left).\" Eye examination revealed a visual acuity of 0.6 in both eyes, intraocular pressures of 19mmHg in the right eye and 8mmHg in the left eye, and congestive conjunctiva in the left eye. The right cornea appeared clear, while the left cornea exhibited a 3mm diameter ulcer below the temporal part, with attached surface fur (see Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The anterior chamber of the right eye displayed moderate clarity with clear aqueous humor, while the left eye exhibited moderate clarity with cloudy aqueous humor. Confocal microscopy revealed abundant myceliform hyperrefraction in the corneal ulcer area of the left eye (see Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), with blurred scanning observed below. The more transparent region at the lesion's edge was scanned to approximately 200\u0026micro;m, revealing concealed mycel-like hyperrefraction with blurred scanning underneath, along with increased inflammatory cells in the stromal layer and blurred cells in the inner cortex. Corneal scrape examination revealed branch-separated mycelium under calcium fluorescence white staining microscopy (see Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Antifungal treatment included natamycin and fluconazole eye drops, along with oral terbinafine tablets. Levofloxacin eye drops were administered to prevent bacterial infection, and praprofen eye drops were prescribed to alleviate anterior chamber reaction. Fungal growth was confirmed through corneal scrape culture (see Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e), with penicillium suspected and subsequently identified through sequencing. After 4 days of treatment, the patient reported reduced foreign body sensation, tearing, and pain in the left eye. Ophthalmic examination showed improved visual acuity (0.6) and decreased intraocular pressure, with reduced congestion and peripheral infiltration in the cornea. Partial repair of the peripheral corneal epithelium was observed, leading to the patient's discharge. Discharge instructions included specific eye drop regimens and oral terbinafine hydrochloride tablets. Follow-up visits were scheduled at regular intervals, during which medication remained consistent and dosage gradually decreased with symptom improvement. One month later, sequencing results confirmed \u003cem\u003eClonostachys rosea\u003c/em\u003e (GenBank No. MN889471.1, 100% similarity). After 35 days, ulcer lesions had formed scars (see Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e), and confocal examination of the corneal focal area revealed normal epithelial cell growth with scar-like reflection below, without obvious mycelial hyperrefraction (see Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCorneal ulcers rank second only to cataracts as a leading cause of blindness in developing countries. Fungal keratitis is increasingly recognized as a significant threat to vision\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e, with Fusarium, Aspergillus, and Candida being the most prevalent causative strains\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e \u003cem\u003eClonostachys rosea\u003c/em\u003e, a filamentous fungus widely found in soil, belongs to the genus Cloradium within the Rubiophoraceae family. It has diverse applications in biological control, fermentation, degradation, and bioenergy\u003csup\u003e[\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e–\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Additionally, it promotes plant growth\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Its mechanisms of action include nutrient competition, hyperparasitism, synthesis of antibacterial substances, and induction of plant disease resistance. On PDA medium at 25°C, the colony of \u003cem\u003eClonostachys rosea\u003c/em\u003e appears white and light orange under fluorescent light. It produces white or light yellow multi-branched septate mycelium, bicyclic or similar primary conidia, penicilliform secondary conidia, and slightly curved distal wide round conidia\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Under specific conditions, chlamydospores can be produced, which exhibit enhanced stress resistance compared to conidia\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe ocular symptoms observed in the patient infected with \u003cem\u003eClonostachys rosea\u003c/em\u003e resembled those commonly seen in filamentous fungal infections, characterized by a 3mm diameter ulcer with moss adhering to the surface. The growth of the corneal scrape culture was rapid, with the appearance of a white colony after 2 days, followed by a transition to yellowish coloration after 6 days. Lactil cotton blue staining revealed branch-separated mycelium, sporulation resembling bottle stems, solitary or penicilliform-like broom structures, and pseudocephalic growth of conidia. Clinical treatment with natamycin eye drops, fluconazole eye drops, and oral terbinafine tablets yielded satisfactory results, leading to scar tissue formation within a month.\u003c/p\u003e \u003cp\u003e\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eAs of now, no infectious diseases linked to \u003cem\u003eClonostachys rosea\u003c/em\u003e have been reported. This case summary aims to contribute to the knowledge and experience in clinical diagnosis and treatment of similar infections.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval and Consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026ldquo;Not applicable\u0026rdquo; in this section.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of supporting data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026ldquo;Not applicable\u0026rdquo; in this section.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026quot;The authors declare that they have no competing interests\u0026quot; in this section.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026ldquo;Not applicable\u0026rdquo; in this section.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXiaona Liu was the major contributor in writing the manuscript.\u0026nbsp;Juanjuan Zheng, Zihan Huo and Feng Wu\u0026nbsp;analyzed and interpreted the result regarding the disease . All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026ldquo;Not applicable\u0026rdquo; in this section.\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003ePriyadarshini SR, Soni T, Sahu SK, et al. Acremonium keratitis: Risk factors, clinical characteristics, management, and outcome in 65 cases. Indian J Ophthalmol. 2022. 70(10): 3522-3527.\u003c/p\u003e\n\u003cp\u003eGarg P, Roy A, Roy S. Update on fungal keratitis. Curr Opin Ophthalmol. 2016. 27(4): 333-9.\u003c/p\u003e\n\u003cp\u003eBiology and applications of\u003cem\u003eClonostachys rosea\u003c/em\u003e. JOURNAL OF APPLIED MICROBIOLOGY. 2020. 129(3): 486-495.\u003c/p\u003e\n\u003cp\u003eMENG F, LV R, CHENG M, al e. Insights into the molecular basis of biocontrol of Botrytis cinerea by \u003cem\u003eClonostachys rosea\u003c/em\u003e in tomato. SCIENTIA HORTICULTURAE. 2022. 291.\u003c/p\u003e\n\u003cp\u003eHan Z, Ghanizadeh H, Zhang H, et al. \u003cem\u003eClonostachys rosea\u003c/em\u003e Promotes Root Growth in Tomato by Secreting Auxin Produced through the Tryptamine Pathway. J Fungi (Basel). 2022. 8(11).\u003c/p\u003e\n\u003cp\u003eMascarin GM, da Silva A, da Silva TP, Kobori NN, Morandi M, Bettiol W. \u003cem\u003eClonostachys rosea\u003c/em\u003e: Production by Submerged Culture and Bioactivity Against Sclerotinia sclerotiorum and Bemisia tabaci. Front Microbiol. 2022. 13: 851000.\u003c/p\u003e\n\u003cp\u003eNtsobi N, Fanadzo M, Le Roes-Hill M, Nchu F. Effects of \u003cem\u003eClonostachys rosea\u003c/em\u003e f. catenula Inoculum on the Composting of Cabbage Wastes and the Endophytic Activities of the Composted Material on Tomatoes and Red Spider Mite Infestation. Microorganisms. 2021. 9(6).\u003c/p\u003e\n\u003cp\u003eVenkatesan RM, Muthusamy K, Iruthayasamy J, et al. First Report of \u003cem\u003eClonostachys rosea\u003c/em\u003e as a Mycoparasite on Sclerotinia sclerotiorum Causing Head Rot of Cabbage in India. Plants (Basel). 2023. 12(1).\u003c/p\u003e\n\u003cp\u003eRAVNSKOV SABINE JB, KNUDSEN INGE MB ea. Soil inoculation with the biocontrol agent \u003cem\u003eClonostachys rosea\u003c/em\u003e and the mycorrhizal fungus Glomus intraradices results in mutual inhibition, plant growth promotion and alteration of soil microbial communities. SOIL BIOLOGY \u0026amp; BIOCHEMISTRY. 2006. 38(12): 3453-3462.\u003c/p\u003e\n\u003cp\u003e Corr\u0026ecirc;a lB, Bettiol W, Morandi MAB. Biological control of Pythium aphanidermatum root rot and growth promotion of hydroponic lettuce by \u003cem\u003eClonostachys rosea\u003c/em\u003e. Sociedade Brasileira de Fitopatologia. 2010. (4).\u003c/p\u003e\n\u003cp\u003e Goh YK, Marzuki NF, Tuan Pa T, et al. Biocontrol and Plant-Growth-Promoting Traits of Talaromyces apiculatus and \u003cem\u003eClonostachys rosea\u003c/em\u003e Consortium against Ganoderma Basal Stem Rot Disease of Oil Palm. Microorganisms. 2020. 8(8).\u003c/p\u003e\n\u003cp\u003e 王琦, 冯静红, 孙占斌等. 氧化胁迫对粉红螺旋聚孢霉生长和产厚垣孢子的影响. 生物技术通报. 2018. 34(4): 6.\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Clonostachys rosea, Keratitis, Fungus","lastPublishedDoi":"10.21203/rs.3.rs-4877880/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4877880/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e There have been no reported cases of infectious diseases associated with \u003cem\u003eClonostachys rosea\u003c/em\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003eThe patient, 53 years old, was admitted with complaints of \"foreign body sensation, tearing, and pain in the left eye for 2 weeks, aggravated for 7 days.\" And was admitted with a diagnosis of \"fungal keratitis (left).\" Fungal growth was confirmed through corneal scrape culture. Antifungal treatment included natamycin and fluconazole eye drops, along with oral terbinafine tablets. Levofloxacin eye drops were administered to prevent bacterial infection, and praprofen eye drops were prescribed to alleviate anterior chamber reaction. After 4 days of treatment, the patient reported reduced foreign body sensation, tearing, and pain in the left eye. Follow-up visits were scheduled at regular intervals, during which medication remained consistent and dosage gradually decreased with symptom improvement. After 35 days, ulcer lesions had formed scars, and confocal examination of the corneal focal area revealed normal epithelial cell growth with scar-like reflection below, without obvious mycelial hyperrefraction.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eHerein, we describe a case of corneal infection attributed to \u003cem\u003eClonostachys rosea\u003c/em\u003e. We outline the development and treatment of this infection to enhance clinical comprehension and management of similar cases.\u003c/p\u003e","manuscriptTitle":"A case of corneal infection with Clonostachys rosea","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-18 02:04:32","doi":"10.21203/rs.3.rs-4877880/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-12-27T18:54:09+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-12T10:44:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"111338150101987760918032346793176613129","date":"2024-12-03T10:08:14+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-03T09:54:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"280875570306768334844792693560495310685","date":"2024-11-28T02:55:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-25T04:03:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"285792513698696517337875833708180041498","date":"2024-11-25T01:43:07+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-18T11:33:33+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-08-09T18:37:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-08T22:54:50+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-08T22:53:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2024-08-08T03:44:58+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7a00a627-56b2-4b4c-8d13-2f2bd955de28","owner":[],"postedDate":"September 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-04-21T16:03:13+00:00","versionOfRecord":{"articleIdentity":"rs-4877880","link":"https://doi.org/10.1186/s12879-025-10903-9","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2025-04-16 15:57:26","publishedOnDateReadable":"April 16th, 2025"},"versionCreatedAt":"2024-09-18 02:04:32","video":"","vorDoi":"10.1186/s12879-025-10903-9","vorDoiUrl":"https://doi.org/10.1186/s12879-025-10903-9","workflowStages":[]},"version":"v1","identity":"rs-4877880","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4877880","identity":"rs-4877880","version":["v1"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}