Characterization ofFusariumKeratitis Outbreak Isolates: Contribution of Biofilms to Antimicrobial Resistance and Pathogenesis
- 1 July 2012
- journal article
- research article
- Published by Association for Research in Vision and Ophthalmology (ARVO) in Investigative Ophthalmology & Visual Science
- Vol. 53 (8), 4450-4457
- https://doi.org/10.1167/iovs.12-9848
Abstract
Purpose.: Fusarium is a major cause of microbial keratitis, and its ability to form biofilms was suggested as a contributing factor in recent outbreaks. We investigated the ability of outbreak Fusarium isolates (F. solani species complex [FSSC] and F. oxysporum species complex [FOSC]) to form biofilms in vitro and in vivo, and evaluated their antifungal susceptibilities. Methods.: Biofilm formation was assessed using our in vitro contact lens model and in vivo murine model. Biofilm architecture was assessed using confocal laser scanning microscopy (CLSM). Susceptibility against amphotericin B (AmB), voriconazole (VCZ), and natamycin (NAT) was determined using the CLSI-M38-A2 method and XTT metabolic assay. Results.: FSSC strains formed more biofilms than FOSC, in a strain- and clade-dependent manner. CLSM analyses revealed that “high biofilm forming” (HBF) strains had denser and thicker biofilms than “low biofilm forming” (LBF) strains of both species (thickness 51 vs. 41 μm for FSSC and 61 vs. 45 μm for FOSC strains, P < 0.05 for both comparisons). Fusarium biofilms exhibited species-dependent antifungal susceptibilities (e.g., FSSC biofilms AmB minimal inhibitory concentrations [MIC] ≥16 μg/mL, while NAT or VCZ MICs were 2–8 μg/mL). FSSC-infected mice had severe corneal opacification independent of biofilm thickness, while FOSC infection resulted in moderate corneal opacification. Corneal fungal burden of mice infected with HBF strains was higher than those of the LBF strains. In contrast, the reference ATCC isolate was unable to cause infection. Conclusions.: The ability to form biofilms is a key pathogenicity determinant of Fusarium, irrespective of the thickness of these biofilms. Further studies are warranted to explore this association in greater detail.This publication has 31 references indexed in Scilit:
- Microbial Biofilms in Ophthalmology and Infectious DiseaseAmerican Journal of Ophthalmology, 2008
- Epidemiological characteristics and laboratory diagnosis of fungal keratitis. A three-year study.2003
- Current Perspectives on Ophthalmic MycosesClinical Microbiology Reviews, 2003
- Mechanism of Fluconazole Resistance in Candida albicans Biofilms: Phase-Specific Role of Efflux Pumps and Membrane SterolsInfection and Immunity, 2003
- Experimental Pulmonary Aspergillosis Due toAspergillus terreus:Pathogenesis and Treatment of an Emerging Fungal Pathogen Resistant to Amphotericin BThe Journal of Infectious Diseases, 2003
- Matrix polymers of Candida biofilms and their possible role in biofilm resistance to antifungal agentsJournal of Antimicrobial Chemotherapy, 2000
- Clinical and microbial spectrum of fungal keratitis in Singapore: a 5-year retrospective studyInternational Ophthalmology, 1997
- Binding ofacanthamoebato hydrogel contact lensesCurrent Eye Research, 1996
- Biofilm-related infections in ophthalmologyEye, 1995
- The Changing Spectrum of Fungal Keratitis in South FloridaOphthalmology, 1994