Chapter 4

Yeasts and
Eukaryotes Normal flora
molds

Decomposers Pathogens
Budding or fission

Sexual production

Spore-former
Overlapping and interlinking

Hyphal filaments

Masses of spores
 Dematiaceous
Color Hyalin

Septate
Hyphae Aseptate

Fungi
 Malassezia furfur
Trichosporon beigelii
Exophiala werneckii
Piedra hortae
Candida albicans
Pityriasis versicolor
White piedra
 Microsporon
Epidermophyton
Trichophyton
 Tinea pedis

Onychomycosis
 Sporothrix schenckii
Fonsecaea pedrosoi
Phialophora verrucosa
Fonseca compactum
Cladosporium carrionii
Pseudalecheria boydii
Phialophora jeanselmei
Madurella mycetomi
Acremonium
Chromoblastomycosis
Mycetoma
 Coccidiodes immitis
Histoplasma capsulatum
Blastomyces dermatitidis
Paracoccidiodes braziliensis
Candida albicans
Blastomycosis
Histoplasmosis
Coccidioidomycosis
Paracoccidioidomycosis
 Candida
Aspergilllus
Rhizopus
Pneumocystis
Edible mushroom
Aspergillus spp. Penicillium spp
Aspergillus spp. Saccharomyces spp
Single-cell protein
Penicillin production
Glucose oxidase
production
Cheese flavoring Roqueforti blue cheese
Gene expression system
Bakers yeast Gene expression system
Brewers yeast Dietary supplement
Invertase
Oomycetes Ascomycytes Basidiomycetes

Deuteromycete
Teliomycetes Ustomycetes
s
Mildews

Water moulds
Mildews

Moulds

Yeasts

Saccharomyces cerevisiae
Mushrooms

Bracket fungi
 Rust Plant
fungi pathogens
 Plant
Smut pathogens
Aspergillus

Fusarium

Penicillium
Chytridiomycota
Zygomycota
Ascomycota
Basidiomycota
 Periplasmic
Cell wall space
Plasmalemma Nucleus

Golgi
Plasmids Mitochondria Ribosomes
apparatus

Endoplasmic Bud and

Vacuoles
reticulum bud scar
Polysaccha-
rides
25%

Glucan 50-60%

Mannan 15-23%
Chitin 1-9%
Branched
-1,6 glucan
polymer
-1,3 glucan
glucose
-1,6,--1,3
inner
complexed
layer with chitin
Polymer of mannose

Outer layer
Concentrated Site of bud
Bud scar detachment

Inner layer
Innermost Chitin
Layer Glucan
Provides
rigidity
Regulating
cell division
 Proteins
Lipids
30% of the CW

Mannoproteins
Formed Polysaccharide
Component
Enzymatic or mechanical removal of cell
wall

Leaves an osmotically fragile protoplast

maintained in osmotically fragile envi.

Resynthesis of cell wall osmotically

stabilized medium

Generate strains with biotechnological

applications
 Below the cell wall

Contains secreted proteins

Location enzymes (Processing of nutrients)

 Below the
Phospholipid
periplasmic
bilayer which
space

Phospholipids,
Ergosterol
lipids, protein,
amphotericin B
sterols
 Sterols

Important components of
plasmalemma

Regions of rigidity in the fluidity

provided by the phosphobilipid layer
 Yeasts

Molds

Dermatophytes
Superficial infections Systemic infections
Oropharyngeal Genital
HIV-positive VVC - 75%

Geriatric 5-12% -
Recurring bouts
Premature
Over a prolong
Immunocompromised period of time
 Dominant Brain,
Pulmonary kidney,
pathogen sinuses

Organ
Leukemia
transplant

Preexisting pulmonary asthma, TB, cystic

lung disease or damage fibrosis, & leukemia
Trichophyton Microsporum
Epidermophyton
 Polyene Azole
Antifungals

Echinocandins Synthetic
Polyene Macrolide ring
carbon atoms

Closed by the
formation internal
ester or lactone

Hydroxyl groups
Amphipathic
Amphotericin
Nystatin
B
Streptomyces
Bind ergosterol
nodosus
Increase
membrane
permeability

Renal toxicity
Formation of
prolonged
pores
therapy
RENAL TOXICITY

Reserve for But recent

severe cases formulations
of systemic which the drug

REDUCED TOXICITY
fungal is encapsulated
diseases within liposomes
Same mode of action as
amphotericin B

Low solubility

Topical infection
 Oral
Effective
Vaginal

Candidosis
First generation azoles

Treatment mucosal and invasive

Most widely used

 Imidazoles

Azole Derivatives
Triazoles

On the basis

2 or 3
Nitrogen atom
5 membered
azole ring
Clotrimazole Miconazole

Econazole Ketoconazole
Itraconazole Fluconazole

Voriconazole
Interfere with Bind to
cytochrome P-450
ergosterol mediated enzyme
biosynthesis (14-- demethylase)

Prevent Reduce
methylation amount of
of lanosterol ergosterol
 Membrane instability

Growth inhibition

Build-up of toxic intermediates

Cell death
 Candida

Cryptococcus

Aspergillus

Dermatophytes
 Miconazole
First used against systemic
Toxic side effects
infection

Ketoconazole high concentration (oral)

Poor against aspergillosis Many side effects

 Fluconazole-1990 (water
soluble) good penetration
and
Pulmonary
deposition
Effective against
tissues, high C. albicans but
levels CSF, not against
peritoneal fluids Aspergillus
 Itraconazole 1980s
fungicidal and fungistatic
effects
30 IV
Effective metabolites formulation
against with widely used
Aspergillus antifungal for
activity Aspergillus
Reduce side effects
Fluconazole

Itraconazole

Compared to

Ketoconazole
 Novel Azole Drug- have a wider
spectrum than fluconazole
Inhibit 14-a
Agents:
demethylase

Voriconazole Posaconazole Ravuconazole

 Voriconazole - is
one of the newest
Good against
2nd generation pulmonary and
triazole cerebral
aspergillosis
 Semisynthetic lipopeptides with a cyclic
hexapeptide core connected to a lateral
fatty acid chain

Caspofungin Micafungin Anidulafungin

Synthesis of -
1,3-glucan
 Aspergillus
Caspofungin-
filamentous
fungistatic
fungi and
yeast Candida
fungicidal
 A. niger
Aspergillus

C. krusei

Candida
A. fumigatus
C. dubliniensis
A. flavus
C. glabrata

A. terreus
Flucytosine(oral antifungal agent)
Fluorinated pyrimidine
Combination with Amphotericin B
Good activity in yeast & moderate Aspergillus spp.
(2 Modes of action) Protein synthesis
Inhibit DNA synthesis
Depletion in AA pools
Candida Aspergilus Histoplasma
albicans fumigatus capsulatum

Cryptococcus
Dermatophytes
neoformans
Opportunistic fungal pathogen

Superficial and systemic infections

GI and renal infections

 Diabetic

Urinary tract
Due to renal
GIT Infection

infection
CA patients Underlying
diseases or cystitis
AIDS
Urinary catheter

Esophagus
cadidiasis

Common site
Immunosuppressive therapy
organ transplantation

Broad-spectrum antibiotic

Can leave into the individual

susceptible - candidiasis
Impaired immune system

Catheterization

Skin damage due burns or trauma

Adhere to host tissue (enzyme activity)

Various mucosal surface

Resist removal from the body

Washing/ bathing
Pathogenic Non-
C. albicans pathogenic
C. tropicalis C. krusei
C.
guilliermondii
Budding blastospores Hyphae
Thigmotropism (contact sensing)

Line of least resistance

Layers of cells
Phospholipases A, B, & C and
lysophospholipases
Damage host cell membrane invasion

Acid proteinases

Adherence, invasion, degradation of IgG

and IgA
Secreted aspartate proteinases
(SAP) - low pH
Colonization of vagina

Hemolysin

Access iron from damaged RBC

 Drug
Adherence
resistance

Enzymes
production
Saprophytic fungus
Decaying vegetation and damp
surfaces
Opportunistic pathogen
Pulmonary aspergillosis 80-90%
Greater mortality rate than
candidosis
Phospholipase tissue
degradation

Proteases tissue degradation

and transport from lung to
bloodstream, neutralization
allergens
Gliotoxin

Helvolic acid, fumigatin,

fumagillin
 AIDS patients

Infants 40-50%
mortality

Elderly with impaired

immune function
In
In Budding
soi Mycelial
tissue
l
 Pulmonary
Macrophages

Yeast cells

Hostile Invade other

Multiply
environment tissue
Encapsulated
AIDS patients
Meningitis
Facultative intracellular
pathogen
Survive within macrophages
Polysaccharides, melanin,
Tinea Microsporum canis

capitis Trichophyton violaceum

Tinea Trichophyton and Microsporum

spp.
corporis Epidermophyton floccosum

Tinea Epidermophyton floccosum

cruris Trychophyton rubrum

 Tinea Epidermophyton floccosum

pedis Trychophyton rubrum

Tinea Trichophyton mentagrophytes

mannum Epidermophyton floccosum

Tinea
Wide range of fungi
unguium
 Non-albicans
Saccharomyces
Candida
cerevisiae
species

Penicillium
marnaffei
 Secondary
Fermentation
metabolites