Biology and Drug Resistance of Candida Biofilms

Summary

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

Top Publications

  1. pmc Metabolomics reveals differential levels of oral metabolites in HIV-infected patients: toward novel diagnostic targets
    Mahmoud A Ghannoum
    Center for Medical Mycology, Case Western Reserve University, Ohio 44106 5028, USA
    OMICS 17:5-15. 2013
  2. pmc Development of a 96-well catheter-based microdilution method to test antifungal susceptibility of Candida biofilms
    Emeka 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
  3. pmc Lipidomics of Candida albicans biofilms reveals phase-dependent production of phospholipid molecular classes and role for lipid rafts in biofilm formation
    Ali 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
  4. pmc Characterization of bacterial communities in venous insufficiency wounds by use of conventional culture and molecular diagnostic methods
    Marie 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
  5. pmc Agar-based disk diffusion assay for susceptibility testing of dermatophytes
    E 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
  6. ncbi Characterization of biofilms formed by Candida parapsilosis, C. metapsilosis, and C. orthopsilosis
    Ali 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
  7. pmc Increased resistance of contact lens-related bacterial biofilms to antimicrobial activity of soft contact lens care solutions
    Loretta 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
  8. ncbi Parenteral lipid emulsion induces germination of Candida albicans and increases biofilm formation on medical catheter surfaces
    Kim Swindell
    Pediatric Infectious Diseases, Children s Hospital, Cleveland Clinic, Cleveland, Ohio, USA
    J Infect Dis 200:473-80. 2009
  9. ncbi In vitro growth and analysis of Candida biofilms
    Jyotsna 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
  10. ncbi Amphotericin B lipid complex is efficacious in the treatment of Candida albicans biofilms using a model of catheter-associated Candida biofilms
    Pranab 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

Scientific Experts

  • Marie S Tuttle
  • Mahmoud A Ghannoum
  • Pranab K Mukherjee
  • Jyotsna Chandra
  • Ali Abdul Lattif
  • Yoshifumi Imamura
  • Kim Swindell
  • Loretta B Szczotka-Flynn
  • Eric Pearlman
  • Emeka I Nweze
  • E I Nweze
  • Mahmoud Rouabhia
  • Saif Hameed
  • Jonathan H Lass
  • Ahmad B Tarabishy
  • Kathleen M Yeater
  • Z Feng
  • Haydee M Ramirez De Knott
  • Guangyin Zhou
  • Thomas S McCormick
  • Patrick M Gillevet
  • Jennifer Webster-Cyriaque
  • Robert E Brown
  • Masoumeh Sikaroodi
  • Richard J Jurevic
  • Mauricio Retuerto
  • Adam Ghannoum
  • Mary R Roth
  • Ruth Welti
  • Michael A Pfaller
  • P K Mukherjee
  • Shawn R Lockhart
  • M A Ghannoum
  • Daniel J Diekema
  • Hyung Gun Kim
  • Lisa Long
  • Changping Yu
  • Kerry O'Donnell
  • Dibyendu Banerjee
  • Tulika Prasad
  • Shyamal K Goswami
  • Yan Sun
  • Aparna Chandra
  • Rajendra Prasad
  • Chinmay K Mukhopadhyay
  • Bishr Aldabagh
  • Lois L Hoyer
  • Georgina Cheng
  • Xiaomin Zhao
  • Sandra L Rodriguez-Zas
  • Kurt E Kwast
  • David Andes
  • Omar S Antar
  • Sotohy Mohamed
  • Ryan Munyon
  • Shuqing Liu
  • Aaron P Mitchell
  • Mark R Chance
  • Duncan Kuhn
  • M Ghannoum
  • B Jiang
  • S Nelson
  • Shaheen Oshtory Do
  • Susan T Nedorost
  • Kevin D Cooper
  • A Weinberg
  • Wendy Goodman
  • J Chandra
  • James M Anderson
  • Jasmine D Patel
  • Jian Li

Detail Information

Publications19

  1. pmc Metabolomics reveals differential levels of oral metabolites in HIV-infected patients: toward novel diagnostic targets
    Mahmoud A Ghannoum
    Center for Medical Mycology, Case Western Reserve University, Ohio 44106 5028, USA
    OMICS 17:5-15. 2013
    ....
  2. pmc Development of a 96-well catheter-based microdilution method to test antifungal susceptibility of Candida biofilms
    Emeka 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...
  3. pmc Lipidomics of Candida albicans biofilms reveals phase-dependent production of phospholipid molecular classes and role for lipid rafts in biofilm formation
    Ali 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...
  4. pmc Characterization of bacterial communities in venous insufficiency wounds by use of conventional culture and molecular diagnostic methods
    Marie 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...
  5. pmc Agar-based disk diffusion assay for susceptibility testing of dermatophytes
    E 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...
  6. ncbi Characterization of biofilms formed by Candida parapsilosis, C. metapsilosis, and C. orthopsilosis
    Ali 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...
  7. pmc Increased resistance of contact lens-related bacterial biofilms to antimicrobial activity of soft contact lens care solutions
    Loretta 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
    ....
  8. ncbi Parenteral lipid emulsion induces germination of Candida albicans and increases biofilm formation on medical catheter surfaces
    Kim 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...
  9. ncbi In vitro growth and analysis of Candida biofilms
    Jyotsna 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...
  10. ncbi Amphotericin B lipid complex is efficacious in the treatment of Candida albicans biofilms using a model of catheter-associated Candida biofilms
    Pranab 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...
  11. pmc MyD88 regulation of Fusarium keratitis is dependent on TLR4 and IL-1R1 but not TLR2
    Ahmad 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...
  12. ncbi Iron deprivation induces EFG1-mediated hyphal development in Candida albicans without affecting biofilm formation
    Saif 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...
  13. pmc Fusarium and Candida albicans biofilms on soft contact lenses: model development, influence of lens type, and susceptibility to lens care solutions
    Yoshifumi 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...
  14. ncbi Temporal analysis of Candida albicans gene expression during biofilm development
    Kathleen 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...
  15. pmc Alcohol dehydrogenase restricts the ability of the pathogen Candida albicans to form a biofilm on catheter surfaces through an ethanol-based mechanism
    Pranab 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...
  16. ncbi Fungal biofilms and antimycotics
    Jyotsna 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...
  17. pmc Modification of surface properties of biomaterials influences the ability of Candida albicans to form biofilms
    Jyotsna 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...
  18. ncbi Cutaneous hypersensitivity to Candida albicans in idiopathic vulvodynia
    Haydee 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...
  19. ncbi Human beta-defensins: differential activity against candidal species and regulation by Candida albicans
    Z 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...