Figure 1. Skin Smear Candida albicans
www.meddean.luc.edu
Candida albicans
Contents
1.
2.
3.
4.
5.
6.
7.
Introduction to Mycology
Biological Profile
Disease capabilities
Pathogenesis
Detection
Drug therapy
Research
The Situation
Frequency
- most common fungal pathogen worldwide
- 4th leading causes of nosocomial infections, 40% mortality
- significant mortality and morbidity in low birth-weight infants
- affects 75% women, 45% experience recurrenceA
> 10 million visits/year
- classified as a STD by CDC
Immunocompromised
- cancer and HIV-AIDs patientsC
- most commonly manifested in patients with leukemia
or HIV-AIDs infections. Oral candidiasis is often a
clue to acute primary infectionC
Public Concerns
- increasing resistance to drug therapies due to antibiotics and
antifungals
Mycology Basics
Kingdom: Fungi
More than 10 million species, but only ~400 human disease (*)
Sexual Groups
Ascomycota*
Basidiomycota*
Zygomycota*
Chytridia
Fungi Imperfecti*
www.ken.coar.org
www.arboretum.harvard.edu
Very few species are in a commensal relationship with humans
- includes Candida albicans and Malasezia furfur
Diseases caused by fungi are usually accidental
www.bio.umass.edu
Endogenous and Exogenous Sources
Increasing problem due to antibacterial & immunosuppressive agents
Molecular mechanisms of pathogenesis not well-defined
The 5 main groups
Figure 1. Classification of Fungi. Fungi are classified
based on their ability to reproduce sexually, asexually, by a
combination of both. The different reproductive structures
places them in the appropriate category. (Baron, 1996)
Fungal Characteristics
Plant-like lacking chlorophyll
Cell wall chitinous matrix
Free-living saprobes and heterotrophs
needs Carbon source and
Nitrogen source
Yeasts or Molds or both
Figure 1. Penicillium chrysogenum www.doctorfungus.org
Success of an infection
Accidental
Overcoming host barriers
Presiding in host with immunological defects
Yeast Characteristics
Mould Characteristics
solitary, unicellular
filamentous hyphae
reproduction via budding
hyphal formation
rounded shape
tips may be rounded
(conidia/spores)
moist & mucoid colonies
Figure 1. Typical Yeast
Figure 2. Typical mould
Yeast Bud Formation
Figure 1. Stages of bud growth and
yeast cell cycle (Baron et. Al., 1996)
Hyphal Formation
Figure 1. Polarized hyphal formation
(Baron et. Al., 1996)
Biology of Candida albicans
Commensal
Pathogen
A thin-walled dimorphic fungus
Morphogenesis
Unicellular yeast (harmeless)
Filamentous (pathogenic)
Principal Cell Wall Polymers
Gluccan
Mannan
Figure 1. Yeast in Oral Scraping
A sample of an oral scraping contains yeast cells and
pseudohyphae
(www.doctorfungus.org)
Strict aerobe, favors moist surfaces
Commensally found in gut, genitals, and lungs
Body Temp 37º C, neutral pH
Rapid Multiplication & Spread
Diseases by C. albicans
Thrush
Esophagitis
Cutaneous Candidiasis
Genital Yeast Infections
Deep Candidiasis
Oropharyngeal Thrush
* Pseudomembranous
* Atrophic
* Angular chelitis
Figure 1. Angular chelitis
(www.emed.com)
Symptoms
Risk Factors
HIV
Treatment: topical
antifungals
Figure 2. Oral Thrush, atrophic
(www.mycolog.com)
Figure 3. Oral Thrush, pseudomembranous
(www.emed.com)
Genital Yeast Candidiasis
Symptoms
Risk Factors
- disruption of normal
microbiota
Figure 1. Vaginal Yeast Culture
(www.euromeds.co.uk)
Treatment
- direct genital administration
- tablets, suppositories, creams
Figure 2. Plasma cell balanitis. A
band-like infiltrate of plasma cells is in
the dermis of the male penis.
(www.webpathology.com)
Deep Candidiasis
Figure 1. Four forms of invasive candidiasis
(www.doctorfungus.org)
Pathogenesis
Host Recognition
Adhesins
Enzymes
Hydrolases: Phosphoplipases, Lipases, Proteinases
Morphogenesis
Yeast form to Filamentous hyphae/pseudohyphae
Phenotypic Switching
Virulence assay of different C. albicans strains using the skin equivalent (AST 2000)
Figure 1. skin equivalent before infection
Figure 2. Infection with pathogenic clinical isolate of C. albicans.
After 48 h the yeast penetrates the skin equivalent and destroys
the tissue
Figure 3. Infection with non-pathogenic C. albicans. This strain is not
able to penetrate into the tissue and thus behaves as avirulent as shown
in the mouse model of systemic infection.
(Fraunhofer, 2002)
MORPHOGENESIS
Figure 1. Morphogenesis.
Morphogenesis in
C. albicans is a pivotal
virulence factor that allows
rapid multiplication and
subsequent dissemination
in host tissue.
(www.kent.ac.uk)
Figure 2. Morphogenic forms of Candida albicans
http://cbr-rbc.nrc-cnrc.gc.ca/thomaslab/candida/caindex.html
Tools for Detection & Diagnosis
Old Methods
Restriction Enzyme Analysis
Current methods
Culture and Serology
PCR Based Molecular Techniques
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
targets SAPs
Advantages
Disadvantages
Future
Non-PCR Based
Fluorescent in situ hybridization
Fig. 1. Throat Swab (www.nlm.nih.gov)
Current Drug Therapies
Major Drug Categories
Polyenes
Problems: Catalase activity, ergosterol production
Azoles
Problems: Enhanced drug efflux
FDA approved antifungal drugs
Amphotericin B (Fungizone)
Clotrimazole (Mycelex)
Fluconazole (Diflucan)
Itraconazole (Sporanox)
Ketoconazole (Nizoral)
Nystatin (Mycostatin)
QuickTi me™ and a
TIFF ( Uncompressed) decompressor
are needed to see thi s pi ctur e.
Fig. 1. Fungizone
(www.bms.se)
Medical Economics. Drug Topics Red Book. Montvale, NJ: Medical Economics
Co., Inc., 2000.
Research
•Biotechnological methods for rapid
identification and detection of Candida
strains
•New antifungal agents
•Molecular pathogenesis
•Emerging opportunistic strains
•Public Health Measures in limiting
nosocomial-related infections
References
1. Bailli e, GS and LJ Doug las. 1999. Ro le of dimorphism i n the deve lopment of
Candida albicans bio film e. J. Med. Microbiol. 48:671-679.
2. Brown , JP. 2002. Morphog enetic Signa li ng Pathways in Candida albicans.
Washington: ASM Press: Candida and Cand idiasis. pp. 95-106.
3. Calderone , R.A. (ed.). Candida and Cand idiasis. Wash ington: ASM Press; 2002.
4. Calderone R and N.A .R. Gow. 2002. Host recogn iti on by Candida species.
Washington: ASM Press: Candida and Cand idiasis. pp. 67-86.
5. Cormack, B.P., N. Ghor i, and s. Falkow. 1999. An adhe sin o f the yea st pathogen
Candidia glabrata mediating adhe renc e to hu ma n ep it heli al cell s. Science 285:
578-582.
6. Ghannou m, MA. 2000. Potential r ole of pho spholi paes in v ir ulence and funga l
pathogene sis. Cli n Micro Review. 13(1): 122-143.
7. Gow, NAR. 2002. Cell Biology and the Cell Cycle of Candida. ASM Press:
Candid a and Cand idiasis. pp. 145-158 .
8. Hawser, SP and LJ Doug las. 1994. Biofilm formation by Candida species on the
surface of catheter materials in vit ro. Infect. Imm uno. 62:915-921.
9. Jabra-Riz k, MA. Et. al. 2004. Fung al Biofilm s and D rug Resistance . Emerging
Infe ctiou s Diseases. 10(1): 14-19.
10. Jarvis , WR. 1995. Epidemi ology of no socomi al funga l infections, with empha sis
on Candida species. Clin Infec Dis . 20(6): 1526-30.
11. Nagli k, J.R. et. Al. 2003. Candida albicans Secreted Aspartyl P roteinases in
Vir ulence and Pathogen esis. Microbiology and Molecular Biology Reviews.
67(3):400-428.
12. Kwong -Chung , K.J. and J .E. Benne tt. 1992. Medical Myco logy. Lea & Febiger,
Phil adelphia.
13. Larone, D.H. 1995. Medicall y Important Fung i – A gu ide to Identifi cation, 3rd
ed. ASM Press, Washington, D.C.
14. Marr Ka. Dec. 2004. Invasive Candida Infections; the changing epidemiology.
Oncology. 18(14 ): 9-14.
15. Medical Econo mi cs. Drug Topics Red Book. Montvale, NJ: Medical Econo mi cs
Co., Inc. , 2000.
16. Mildvan, D. (ed.). 1995. Atlas of Infectious Diseases, vol. I. Current
D. www .webpathology.com
C. http:/ /www.ncb i. nlm .nih.gov
B. http:/ /www.e me dicine.co m/ emerg/topic76.htm
A. http:/ /www. inteli hea lt h.com/ IH/ihtIH/WSIHW000/9339/31092.h tml
Medicine Inc., New York, New Y ork.
17. Prescott, LM et. al., Mi crobiology. NY: McGraw-H ill; 2002.
18. Soll DR. 1992. High F requency Switching in Candida albicans. Clin
Micro Review. 5(2): 183-203.
19. Sulliv an DJ and DC Coleman. 2002. Molecular Approaches to
Identification and Typing o f Candida Species. ASM Press: Cand ida and
Candidi asis.
20. Suzuk i, S. 2002. Serological diff erences a mong the pathogen ic Candida spp.
ASM: Candida and Candidiasis. pp. 29-36 .
21. Raoul t, D. et. al.. 2004. Wha t does the future ho ld for cli nical mi crobiology?
Nature Reviews. 2: 151-159.
22. Ruhnk e, M. 2002. Skin and Mucous Me mbrane Infections. ASM Press:
Candida and Candidiasis. pp. 307-325 .
23. Burnie J. & R. Matthews. 2003. The role of antibodies against hsp90 in the treatment of fungal infections
Drug News Perspect 16(4): 205-210.