General and Systemic

Mycology

Dr. Berek Zsuzsanna

02 February 2010
 Introduction
Fungal diseases
1. Allergy / asthma (spores)
2. Mycotoxicosis: e.g. aflatoxins, ochratoxins
3. Mycosis – infections caused by fungi
• acute, subacute, chronic
• local – general/systemic
medical mycology
 WHERE to see mycoses?

™ skin + adnexes, mucosal surfaces (local)

™ internal organs – anywhere (systemic)
- lung
- central nervous system
- urogenital tract
- GI tract etc.
General mycology
Final exam questions
IV. / 1 - 6
Structure, metabolism, life cycle and
classification of medically important
fungi (IV./1)

Eukaryotic! Saprophitic!
• Structure
- cell wall – Glucane, Mannane, Chitin,
Mannoprotein
- cell membrane – ergosterole
- 80s rRNA
- microtubuli (tubulin)
 mannoprotein

glucan+chitin
www.scielo.org.ve

mannoprotein
Structure, metabolism, life cycle and
classification of medically important
fungi (IV./1)

Fungi are
U Yeasts
a Candida spp.
a Cryptococcus neoformans
unicellular
solitaer round/ovale shape, ca. 5–8 μm
multiplication: budding
Medmicro 73-4
Structure, metabolism, life cycle and
classification of medically important
fungi (IV./1)
Fungi are
UU Molds
7 Aspergillus Hypha = filament
7 Penicillium septated/non septate
7 Mucor filament diameter 2-10 μm
multicellular
mats of filaments/hyphae: mycelium
Fungal colony: thallus
mycelium: septate mycelium: non septate
 Multiplication

Filaments –
Hypha Hyphae-form
Mycelium

Yeast
Pseudohypha
Budding Kaiser’s Abb. 6.1
Structure, metabolism, life cycle and
classification of medically important
fungi (IV./1)
Fungi are
UUU Dimorphic
25˚C – molds, 37 ˚C – yeasts
V Histoplasma
V Blastomyces (Paracoccidiodes)
V Coccidioides (spherule!)
œ Sporothrix schenkii
 !!

Medmicro 75-3
Structure, metabolism, life cycle and
classification of medically important
fungi (IV./1)
Metabolism
• aerobic
• C- and N-source
• pH – mild acidic (5,6)
• MOIST! (dark!)
• Temperature: wide optimum, 37˚C!
Structure, metabolism, life cycle and
classification of medically important
fungi (IV./1)

Life cycle/reproduction
Growing (vegetative life cycle)
Reproduction
Sexual – with spores (teleomorph)
Asexual – with conidia (anamorph)
Parasexual
 Asexual reproduction: Spores = Conidia

Sporangiospores
Conidia
(Makro- , Mikro-)

Blastospores
(Conidia)

Arthrospores
(Conidia)

Chlamydospores
(Conidia)
 Asexual reproduction: Spores = Conidia

Sporangiospores
Conidia
(Makro- , Mikro-)

Blastospores
(Conidia)

Arthrospores
(Conidia)

Chlamydospores
(Conidia)
 Asexual reproduction: Spores = Conidia

Sporangiospores
Conidia
(Makro- , Mikro-)

Blastospores
(Conidia)

Arthrospores
(Conidia)

Chlamydospores
(Conidia)
 Asexual reproduction: Spores = Conidia

Sporangiospores
Conidia
(Makro- , Mikro-)

Blastospores
(Conidia)

Arthrospores
(Conidia)

Chlamydospores
(Conidia)
 Asexual reproduction: Spores = Conidia

Sporangiospores
Conidia
(Makro- , Mikro-)

Blastospores
(Conidia)

Arthrospores
(Conidia)

Chlamydospores
(Conidia)
 Sexual Reproduction (teleomorph) and
Taxonomy
Classes
ZYGOMYCOTA
Zygospores (sex)
Sporangiospores (asex)
ASCOMYCOTA
Ascospores (sex)
Conidia (asex)
BASIDIOMYCOTA
Basidiospores (sex)
Conidia (asex)
DEUTEROMYCOTA = Fungi imperfecti
(only Conidia known!)
Fungi imperfecti – Try to classify us…
You’re not my type…
And anyway:
I can make it on my own …

Yeasts have both sexual and asexual reproduction

 Structure, metabolism, life cycle and
classification of medically important
fungi (IV./1)
Classification
- taxonomy v/s medical importance, filogenesis:
teleomorphs!

BUT: in medical mycology we see asexual forms!

Details: see book! Murray: chapter 7

 Mycoses: classification and
pathogenesis (IV./2)
• Acute • Dermatomycoses
• Subacute - superficial
• Chronic - cutaneous
• Subcutaneous
• Local mycoses
• General, deep, • Systemic mycoses
invasive, systemic
infections
 skin + connective tissue

Chapter 72,73!

Medmicro 75-1
 Mycoses: classification and
pathogenesis (IV./2)
Dermatomycoses
- local, skin and other keratinized tissues
- causative agents: dermatophytes
› Trichophyton
› Epidermophyton keratinophilic!
› Microsporum
dermatophytoses!
 Mycoses: classification and
pathogenesis (IV./2)
Subcutan mycoses
- local granuloma formation Î spread: via lymphatics
Sporothrichosis (S. schenkii)
Chromomycosis (Phialophora spp.)
Chromoblastomycosis (Fonsecaea spp.)
Maduromycosis/mycetoma (mixed!)
TRAUMA!
 Mycoses: classification and
pathogenesis (IV./2)
Systemic mycoses
Primary v/s opportunistic pathogens
Õ Primary pathogens – intact immune system
C. immitis, H. capsulatum, B. dermatitidis,
P. brasiliensis
Dimorphic, exogen source,
inhalation Î lung
 Mycoses: classification and
pathogenesis (IV./2)
Õ Opportunistic pathogens –
immunocompromised host
C. neoformans, Candida spp. (yeasts),
Aspergillus spp., Penicillium and other molds
- exogen or endogen source (Candida!)
- portal of entry variable, different
clinical findings
 Primary pathogenic and opportunistic pathogenic fungi

PORTAL OF ENTRY

Medmicro 75-2
 Microbiological diagnosis of fungal
infections (IV./5), cultivation of fungi
(IV./4)
•Sample collection
•Microscopic examination
•CULTIVATION
•Identification
•Susceptibility test (MIC!) of antifungal drugs
ÏPractice!Ï
Serology, skin tests
 Treatment of fungal infections
(IV./6)

Antifungal, antimycotic drugs

Application
• Local
- solutions, creams, powders, nail-polish etc.
• Systemic
- parenteral, per os
 Antifungal chemotherapy – modes of action
2. 3.
1.

4. Allylamines
amorolphine

6. Echinocandin

5. Griseofulvin – microtubules, mitosis inhibition

Medmicro 76-2
 Treatment of fungal infections
(IV./6)

1. Polyenes
Produced by Streptomyces
Nystatin (topical)
Amphotericin B
2. 5-fluorocytosin
inhibit nucleic acid synthesis
 Treatment of fungal infections
(IV./6)

3. Azoles
Imidazoles
Ketoconazol, clotrimazol, miconazol etc.
Triazoles
Itraconazol
Fluconazol
Inhibition of ergosterol synthesis, cytochrome P450
 Treatment of fungal infections
(IV./6)

4. Allylamines, Morpholin
Naftifine
Terbinafin
Amorolphine
- inhibit ergosterol biosynthesis, different
biochemical steps
 Treatment of fungal infections
(IV./6)
5. Griseofulvin
Produced by Penicillium griseofulvum
Inhibition of microtubules (mitotic spindle)
Î no mitosis Î no fungus multiplication

Dermatophytoses only!
6. Echinocandin, Caspofungin
Inhibition of cell wall glucan synthesis
 Risk- and predisposing factors of
mycoses (IV./3)

IMMUNOCOMPETENT IMMUNOCOMPROMISED
1. Enviroment Cellular
- moisty 1. HIV/AIDS
- warm 2. Haematological
2. AB therapy malignancies
3.Pregnancy, oral - leukaemias, lymphomas
contraceptives 3. Transplantation
4. Diabetes mellitus 4. Therapy
+1 Others (AGE!) - radio-, corticosteroid
Systemic mycology
Final exam questions
IV. / 7 - 14
Mycoses: skin+adnexes (IV ./ 7) and
subcutaneous mycoses (IV./8)

Dermatomycoses Subcutan mycoses

- local granuloma formation Î
- local, keratinized
spread: via lymphatics
tissues
” Sporothrichosis (S. schenkii)
- causative agents: ” Chromomycosis
adermatophytes (Phialophora spp.)
dermatophytoses! ” Chromoblastomycosis
Keratinophilic! (Fonsecaea spp.)
” Maduromycosis/mycetoma
a Candida spp.
(mixed!)
TRAUMA!
 skin + connective tissues

Medmicro 75-1
 Dermatophytes
Molds
›Trichophyton
T. rubrum, T. concentricum
›Epidermophyton
E. floccosum local discharge
›Microsporum with inflammation
M. gypseum
 Dermatophytoses 1.
T. rubrum Tinea cruris
Forrás: dermatologie.free.fr
 Dermatophytoses 2.

Tinea pedis
T. rubrum

plant

(Sabouraud medium)

Forrás: www.mycology.adelaide.edu.au és forlag.fadl.dk

 Dermatophytoses 3.

M. gypseum

Tinea capitis – M. gypseum

Forrás: www.mycology.adelaide.edu.au és www.lib.uiowa.edu
 Dermatophytoses 4.
before treatment after

Epidermophyton floccosum

„jock-itch”
Forrás: www.mycology.adelaide.edu.au és www.mycolog.com ch.23
Dermatophytoses 5.

-onychomycosis
-Epidermophyton or Trichophyton destroying the toenails.
 Dermatophytoses 6.

Onychomycosis Epidermophyton or Trichophyton

 Skin mycoses caused by
yeasts

Skin with pustules

Perianal region
Forrás: www.mycology.adelaide.edu.au és www.emedicine.com
 Superficial mycoses

Malassezia furfur (PAS)

No local
inflammation!

and pityriasis versicolor

Forrás: www.mf.uni-lj.si
Forlag.fadl.dk, www.
bioltrop.org
 Subcutan mycoses (IV./8)

Subcutan mycoses
- local granuloma formation Î spread: via lymphatics
œ Sporothrichosis (S. schenkii)
Chromomycosis (Phialophora spp.)
Chromoblastomycosis (Fonsecaea spp.)
Maduromycosis/mycetoma (mixed!)
TRAUMA!
 Sporothrix schenkii 1.
Dimorphism

conidia
 Sporothrix schenkii 2.

37˚C: yeast cells

 Sporothrix schenkii 3.

Colonies: creamy-butterwhite 37˚C

 Sporothrix schenkii 4.

Colonies: brown – black 25˚C

 Sporotrichosis

Tissue: asteroid cells

Forrás: www.vet,ed.visc.edu és www.mycolog.com ch.23

 Subcutan mycoses (IV./8)
Subcutan mycoses
- local granuloma formation Î spreading: via lymphatics
Sporothrichosis (S. schenkii)
œChromomycosis (Phialophora spp.)
œChromoblastomycosis (Fonsecaea spp.)
Maduromycosis/mycetoma (mixed!)
TRAUMA!
 Chromo/blasto/mycoses 1.

Forrás: www.visualsunlimited.com és www.mycolog.com ch23

Chromo/blasto/mycoses 2.

57 years old farmer

thick, induration, viola

Forrás: dermatlas.med.jhmi.edu és tray.dermatology.uiowa.edu

 Subcutan mycoses (IV./8)
Subcutan mycoses
- local granuloma formation Î spread: via lymhatics
Sporothrichosis (S. schenkii)
Chromomycosis (Phialophora spp.)
Chromoblastomycosis (Fonsecaea spp.)
œ Maduromycosis/mycetoma (mixed!)
TRAUMA!
 Maduromycoses 1.
Fig. 13-13. Madura foot,
caused by
Pseudoallescheria boydii
(Textbook: Fungal diseases of Man)

Forrás: www.angelfire.com/…/textbook
 Maduromycoses 2.
X-RAY
calcanectomy

24 years old man, 2000

maduromycosis in scar

Forrás: selianlh.habari.co.tz
 Maduromycoses 3.
37 yrs old man, complains for 7 yrs
(non diabetic)

Forrás: www.orthogate.com
 Opportunistic
Mycoses caused by
Yeasts
 Candida genus (IV./15)

• C. albicans
• C. glabrata, C. krusei
• C. pseudotropcalis, C. tropicalis, C. lusitaniae
- Yeast
- Endogen source
Clinical findings:
candidiasis/candidosis
 Candida albicans
Normal flora member
- skin
- mucosal surfaces

Forrás: Medmicro fig.75-4

 Candida albicans
Pathogenesis: Adhaesion
Adhaesins
A) Hydrophobic surface proteins
Receptors: Hydrophobic surfaces: Epithelial cells (skin,
mucosa), foreign bodies
B) Lektin-like and integrin-like proteins of Candida
Receptors: Proteins, Glykoproteins of
Epithelcells, Endothelcells, Extracellular Matrix (ECM),
Blood, Dental film (oral cavity), Biofilm
Streptococcal Polysaccharides (oral cavity)
Glycosphingolipids
ADHAESION

Thrombocytes

Plastik

Mannoprotein of Candida
 Candidiasis
Normal flora ballance is lost

Immune competent Immunocompromised

LOCAL LOCAL
- Soor General oral candidiasis
- Vaginal fluor Oesophagitis (AIDS!)
- Interdigital mycosis Chronic mucosal
- Intertrigo SYSTEMIC
SYSTEMIC Pneumonia
- Candida sepsis (rare!) Endocarditis
Sepsis
-thrush or buccal
candidiasis – soor

Candida albicans.
Forrás: www.horinouchi.or.jp
Gesichts - Soor Roche Bildatlas Candidiasis granulomatosa
Imprint of a
prothesis on
Sabouraud agar

Candida albicans

Merck diagnostics
Mycosis - tongue Roche Bildatlas
Soor – Throat Roche Bildatlas
Interdigital mycosis
Submammal intertrigo
 - intertrigo Candida albicans

inguinal

perianal

Forrás: www.udl.es
Candida vulvovaginitis
www.uff.br/dst
Candidiasis

www.uff.br/dst
 New-born, infants

Candida sepsis
„Nappy” candidiasis -Premature
- dissemination -Ab therapy
Forrás: www.mycology.adelaide.edu.au -Intravascular devices
Haematogen Dissemination Abscesses in Kidney
 HIV/AIDS 1.

tongue

Oral candidiasis

Forrás: www.hivguidelines.org., medlib.med.utah.edu

 Candida oesophagitis - endoscopy

HIV/AIDS 2.

Forrás: www.hkcfp.org.hk, www.endo-world.com

 Cryptococcus neoformans
(IV./12)
œ Opportunistic pathogen –
immunocompromised host
- yeast, exogen source (bird faeces, soil, inhalation)
- Virulence factor: CAPSULE!
- Clinical findings: granulomatous lesions,
Lung cryptococcosis;
dissemination: meningoencephalitis
- Therapy: flucytosine, amphotericinB
 Cryptococcus neoformans 1.

Forrás: www.bioteach.ubc.ca
Cryptococcus neoformans 2.
Capsule staining: ink-preparates

Forrás: www.niaid.nih.gov, medecinetropicale.free.fr,

www.som.tulane.edu
 Cryptococcus neoformans 3.

Culture: Sabouraud agar - yellowish mucoid colonies

Forrás: www.mycology.adelaide.edu.au
Cryptococcus neoformans 4.

HIV positive patients

Forrás: dermatlas.med.jhml.edu
 Cryptococcus neoformans 7.
-48 years old
-ciprofloxacin
-diabetes mellitus
-liver transplantation
-prednisone
Figure 1. Solitary
erythematous nodule on Figure 3. Gomori's
the medial aspect of the methenamine-silver stain
foot revealing numerous yeast-like
organisms

Figure 4. Cryptococcal capsules

stained positively with
mucicarmine
Forrás: www.mf.uni-lj.si
 Opportunistic
Mycoses caused by
Molds
 Aspergillus species and
Penicillium genus (IV./13)
Molds – opportunistic mycoses
Aspergillus
175 species, 16 human pathogens
A. fumigatus, A. flavus, A. niger etc.
Local aspergillosis:
- eye, external ear, sinuses
Aspergillosis – internal organs:
- lung, central nervous system
 Production of
Penicillium antibiotics

Spores in the air

Together:
Penicillium (grey)
and
Aspergillus flavus
(yellow)
 Aspergillus - aspergillosis
A. flavus

Forrás: www.aflatoxin.info, www.hpa.org.uk, www.univ-brest.fr, www.kgain.com

 Aspergillus - aspergillosis
Lung – A. fumigatus

Hyphae – methenamin silver stain

Brain abscess

conidium

Forrás: www.humpath.com, www.mycology.adelaide.edu.au

Fig. 12.52 Fungal
keratitis. Corneal
ulcer due to
Aspergillus flavus
infection.
By courtesy of
Prof. R. Y.
Cartwright.
Fig. 12.53 Fungal keratitis. Fungal hyphae seen on corneal scraping. By
courtesy of Mr. P.A. Hunter
 Zygo- (phyco) mycoses (IV./14)

Mucor-mycoses
Causative agent: many species
Mucor, Rhizopus, Rhizomucor
very invasive, grow fast
Clinical findings:
variable, immunocompromised hosts!
Rhinocerebral
Pulmonal
 Zygo- (phyco) mycoses (IV./14)

Rhizomucor

R. pusillus – growth on 45˚C

Forrás: www.fungus-fungi-fungal.com, helios.bto.ed.ac.uk

Zygo- (phyco) mycoses (IV./14)

Rhinocerebral Mucor-mycosis

Forrás: www.mycolog.com ch23

Zygo- (Phyco-) mycoses

Fig. 12.17 Rhinocerebral

mucormycosis. Advanced case
with necrosis of nasal axillary
tissue and black eschar. Note the
periorbital oedema and
serosanguinous discharge from
the eye. By courtesy of Prof. R.
Y. Cartwright.
Fig. 12.16 Rhinocerebral mucormycosis. View through nasal speculum
showing fungal material arising from nasal turbinates. By courtesy of Prof. R.
Y. Cartwright.
Fig. 12.18 Rhinocerebral mucormycosis. Mucor organism visible in biopsy,
showing irregular branching hyphae and sporangia. By courtesy of Prof. R. Y.
Cartwright.
Primary Systemic
mycoses
 Coccidioides immitis (IV./9)
Blastomyces dermatitidis (IV./10)
Histoplasma capsulatum (IV./11)

ÕPrimary pathogens – immunocompetent

systemic mycoses
Dimorphic, exogen source,
inhalation Î lung Î dissemination
(surviving phagocytosis in the alveolar macrophages!)
Therapy: amphotericin B
Geographical distribution: American continent
 Coccidioides immitis 1.
soil

arthospores

inhalation

Forrás: Medmicro FigM1

 Coccidioides immitis 2.

dissemination

biopsy
spherule diameter ca. 30–60 µm

culture
Forrás: www.mycology.adelaide.edu.au és www.bioltrop.org és www.mycolog.com ch23
 Blastomyces dermatitidis
(IV./10)
(Paracoccidioides brasiliensis)

Yeast, budding
blastoconidia
Forrás: botit.botany.wisc.edu
 Blastomyces dermatitidis 2.

Forrás: www.vetmed.ufl.edu Chr. multifocal granulomatous pneumonia

 Blastomyces dermatitidis 3.

Forrás: www.mycolog.com ch23 és www.doctorfungus.org

 Blastomyces dermatitidis 4.

dissemination

Culture: molds

Blastomycosis
X-RAY, bronchoscopy confirmation
Forrás: www.emedicine.com, www.vetmed.wisc.edu,www.mycolog.com ch23
 Histoplasma capsulatum IV./11

culture

Lung: round, yeast cells

EM
Forrás: www.mold.ph/toxic_mold, www.cat.cc.md.us - cdc anyaga
 Histoplasma capsulatum 2.

Lymph node Î phagocytosed

yeast cells
Lung: granuloma
Forrás: www.som.tulane.edu
Histoplasma capsulatum 3.

Histoplasmosis

Forrás: medecinetropicale.free.fr
Fungus – but just because the rRNA test showed
Morphology – protozoon
Pathogenesis – protozoon
Didactically – protozoon (books!) …
 THE END!

Cyprus, 2008 December