Biology and Drug Resistance of Candida Biofilms
Principal Investigator: M A Ghannoum
Abstract: DESCRIPTION (provided by the applicant): Candida-associated denture stomatitis (chronic atrophic candidiasis) is the most prevalent superficial oral infection and the most common form of Candida-associated disease. The etiology of denture stomatitis involves dental plaque. Dental plaque consists of a complex biofilm of bacteria and yeasts, predominantly Candida albicans. C. albicans biofilms have received much less attention than bacterial biofilms, and our present knowledge of their biology and drug resistance is at a rudimentary stage. Frequent denture stomatitis treatment failures combined with a steadily increasing population of elderly people, many of whom will be endentulous, make this area of study particularly important. The long-range goal of our work is to understand the biology and drug resistance of C. albicans biofilms. Our preliminary work in this new area resulted in the successful development of a reproducible model of C. albicans-associated biofilms (Publication #1). Since the last submission, we used this model to: 1) define the three stages of C. albicans associated biofilm development, 2) demonstrate that C. albicans biofilm is a highly heterogeneous structure, 3) show that the antifungal resistance of C. albicans biofilm increases in conjunction with biofilm development, 4) show that C. albicans has greater ability than the less pathogenic C. parapsilosis and Saccharomyces cerevisiae to form denture biofilm, and 5) show that C. albicans genes are differentially expressed under biofilm and planktonic conditions. Additionally, we initiated efforts to construct a C. albicans DNA array, and developed a bioprosthetic associated candidal biofilm model. Importantly, our studies showed that biofilm grown in our in vitro model has similar morphology as that growing in vivo on a catheter obtained from a patient with catheter-associated infection. Specific aims of the current proposal are: Specific Aim 1: Use our established biofilm model to determine the antifungal susceptibility profiles of C. albicans isolates obtained from denture stomatitis patients, and to study the effect of antifungal agents on the growth kinetics of C. albicans bioflims. Specific Aim 2: Investigate the mechanism(s) responsible for increased antifungal resistance of biofilm-associated C. albicans. Specific Aim 3: Identify genes that are involved in the formation and contribute to the development of antifungal resistance of C. albicans biofilms. By studying biofilm model systems and applying this knowledge to the patient population, we will gain a wealth of data about the biology and drug resistance of C. albicans in biofilms.
Funding Period: 2002-03-01 - 2006-12-31
more information: NIH RePORT
- Metabolomics reveals differential levels of oral metabolites in HIV-infected patients: toward novel diagnostic targetsMahmoud A Ghannoum
Center for Medical Mycology, Case Western Reserve University, Ohio 44106 5028, USA
OMICS 17:5-15. 2013....
- Development of a 96-well catheter-based microdilution method to test antifungal susceptibility of Candida biofilmsEmeka I Nweze
Center for Medical Mycology, Department of Dermatology, School of Medicine, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, OH 44106 5028, USA
J Antimicrob Chemother 67:149-53. 2012..We describe a simple, reproducible catheter-based microtitre plate method to form biofilms and evaluate their antifungal susceptibility...
- Lipidomics of Candida albicans biofilms reveals phase-dependent production of phospholipid molecular classes and role for lipid rafts in biofilm formationAli Abdul Lattif
Center for Medical Mycology, University Hospitals Case Medical Center, and Department of Dermatology, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106 502, USA
Microbiology 157:3232-42. 2011..albicans to form biofilms. The differences in lipid profiles between biofilms and planktonic Candida cells may have important implications for the biology and antifungal resistance of biofilms...
- Characterization of bacterial communities in venous insufficiency wounds by use of conventional culture and molecular diagnostic methodsMarie S Tuttle
Case Western Reserve University, University Hospitals Case Medical Center, Department of Dermatology, Cleveland, OH 44106, USA
J Clin Microbiol 49:3812-9. 2011..Thus, pyrosequencing identified distinctive baseline characteristics of wounds that did not heal by the 6-month follow-up, furthering our understanding of potentially unique microbiome characteristics of chronic wounds...
- Agar-based disk diffusion assay for susceptibility testing of dermatophytesE I Nweze
Center for Medical Mycology, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH 44106, USA
J Clin Microbiol 48:3750-2. 2010..Our results show that the method is reproducible, is simple, and could be used to determine the antifungal susceptibility of dermatophytes...
- Characterization of biofilms formed by Candida parapsilosis, C. metapsilosis, and C. orthopsilosisAli Abdul Lattif
Center for Medical Mycology, Department of Dermatology, University Hospital s Case Medical Center, and Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106 502, USA
Int J Med Microbiol 300:265-70. 2010..These results demonstrate that similar to C. parapsilosis, the 2 newly identified Candida species (C. orthopsilosis and C. metapsilosis) were able to form biofilms...
- Increased resistance of contact lens-related bacterial biofilms to antimicrobial activity of soft contact lens care solutionsLoretta B Szczotka-Flynn
Department of Ophthalmology and Visual Sciences, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH 44106, USA
Cornea 28:918-26. 2009....
- Parenteral lipid emulsion induces germination of Candida albicans and increases biofilm formation on medical catheter surfacesKim Swindell
Pediatric Infectious Diseases, Children s Hospital, Cleveland Clinic, Cleveland, Ohio, USA
J Infect Dis 200:473-80. 2009..No studies have addressed the effect of LE on candidal biofilm production. In this study, we investigated the effect of LE on candidal germination and its ability to form biofilm on medical catheter material...
- In vitro growth and analysis of Candida biofilmsJyotsna Chandra
Center for Medical Mycology and Department of Dermatology, University Hospitals Case Medical Center, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, Ohio 44106, USA
Nat Protoc 3:1909-24. 2008..The methods described here can be completed in a typical laboratory with minimum involvement of software. Evaluation of the growth of fungal biofilms and their analyses can be completed using the described methods in approximately 15 d...
- Amphotericin B lipid complex is efficacious in the treatment of Candida albicans biofilms using a model of catheter-associated Candida biofilmsPranab K Mukherjee
Center for Medical Mycology, Department of Dermatology, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH 44106 5028, USA
Int J Antimicrob Agents 33:149-53. 2009..Taken together, these studies demonstrated that using ABLC it was possible to sterilise catheters on which C. albicans biofilms were formed...
- MyD88 regulation of Fusarium keratitis is dependent on TLR4 and IL-1R1 but not TLR2Ahmad B Tarabishy
Department of Ophthalmology and Visual Sciences, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, OH 44106, USA
J Immunol 181:593-600. 2008..Together, these findings indicate that IL-1R1 and MyD88 regulate CXC chemokine production and neutrophil recruitment to the cornea, and that TLR4 has an important role in controlling growth and replication of these pathogenic fungi...
- Iron deprivation induces EFG1-mediated hyphal development in Candida albicans without affecting biofilm formationSaif Hameed
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
FEMS Yeast Res 8:744-55. 2008..albicans cells. Our study, for the first time, establishes a link between cellular iron, Efg1p and hyphal development of C. albicans cells that is independent of biofilm formation...
- Fusarium and Candida albicans biofilms on soft contact lenses: model development, influence of lens type, and susceptibility to lens care solutionsYoshifumi Imamura
Center for Medical Mycology, University Hospitals Case Medical Center and Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106, USA
Antimicrob Agents Chemother 52:171-82. 2008..This in vitro model should provide a better understanding of the biology and pathogenesis of lens-related fungal keratitis...
- Temporal analysis of Candida albicans gene expression during biofilm developmentKathleen M Yeater
Department of Pathobiology, University of Illinois, Urbana, IL 61802, USA
Microbiology 153:2373-85. 2007..Collectively, these data suggest that genes belonging to different, but interconnected, functional categories regulate the morphology and phenotype of C. albicans biofilm...
- Alcohol dehydrogenase restricts the ability of the pathogen Candida albicans to form a biofilm on catheter surfaces through an ethanol-based mechanismPranab K Mukherjee
Center for Medical Mycology, Department of Dermatology, Case Western Reserve University, 11100 Euclid Avenue, LKS 5028, Cleveland, OH 44106, USA
Infect Immun 74:3804-16. 2006..albicans to form biofilms in vitro and in vivo and that the protein restricts biofilm formation through an ethanol-dependent mechanism. These results are clinically relevant and may suggest novel antibiofilm treatment strategies...
- Fungal biofilms and antimycoticsJyotsna Chandra
Center for Medical Mycology, Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106 5028, USA
Curr Drug Targets 6:887-94. 2005..This review discusses methods used to evaluate biofilm resistance and provide information on susceptibility pattern of candidal biofilm as well as studies investigating the mechanisms underlying biofilm resistance...
- Modification of surface properties of biomaterials influences the ability of Candida albicans to form biofilmsJyotsna Chandra
Center for Medical Mycology, Department of Dermatology, University Hospitals of Cleveland and Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106 5028, USA
Appl Environ Microbiol 71:8795-801. 2005..40). This study illustrates that surface modification is a viable approach for identifying surfaces that have antibiofilm characteristics. Investigations into the clinical utility of the identified surfaces are warranted...
- Cutaneous hypersensitivity to Candida albicans in idiopathic vulvodyniaHaydee M Ramirez De Knott
Department of Dermatology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA
Contact Dermatitis 53:214-8. 2005..Low levels of C. albicans may also be required to elicit this response as high levels of C. albicans may actually result in decreased cutaneous inflammation and decreased intensity of C. albicans patch test responses...
- Human beta-defensins: differential activity against candidal species and regulation by Candida albicansZ Feng
Department of Biological Sciences, Case Western Reserve University School of Dental Medicine, 10900 Euclid Avenue, Cleveland, OH 44106 4905, USA
J Dent Res 84:445-50. 2005..albicans suggests disruption of the fungal membrane. Results support the hypothesis that hBDs control fungal colonization through hyphal induction, direct fungicidal activity, and inhibition of candidal adherence...