Fungi
Fungi • Ubiquitous in the environment • Mushrooms • Mold • Yeast • Used frequently in food and pharmacy applications • Some are are considered microbes - but eukaryotic • Very few species in human flora • Candida albicans (yeast) • Oral • Gut • Vaginal • Commensal unless something happens with the host
Fungi→ Molds and Yeast
Mold and Yeast are ____
Both are microscopic ____ ___ organisms
Fungi→ Molds and Yeast Mold and Yeast are Microbes Both are microscopic single celled organisms • Molds make filamentous hyphae • Yeast are cellular→circular in shape
Helpful Fungi
Helpful Fungi • Food and Pharmacy • Saccharomyces cerevisiae: (Bakers yeast) • Helps yeast rise • Yeast fermentation of sugar forms CO2 • Yeast break down glucose and make CO2 • They also release ethanol so used to make beer and wine • Penicillin is byproduct of penicillium • Cheese needs fungi • Penicillium roquefortii • Penicillium camenbertii
Environmental Molds & Fungi
Eating dead organic matter (_____) in moist dark areas.
Environmental Molds & Fungi Eating dead organic matter (saprophytes) in moist dark areas.
Candida albicans – “a fungus among us”
Can be in ___ form or ___ form and can switch back and forth
Candida albicans – “a fungus among us” • A resident of all mucosal surfaces and dental plaque • Candidiasis • “Thrush” • Mold and fungus is everyehere • They are sachrophytes so only eat dead material • Like moisture, dark areas • Very rare to get fungal infection from environment. • If you do, you generally have a health issue • Candida albicans is a yeast • Tiny granules are bacteria, longer forms are candida. • Candida is dymorphic. Can be in yeast form or hyphae form and can switch back and forth
What does “Candida albicans” mean?
What does “Candida albicans” mean? • Candidas→White • Candidate for office wears white toga • Candid→ pure and honest • When you grow them in lab, you have large white colony formed • Albicans is from alba which also means white!
Fungi are eukaryotes
Idealized yeast cell
Candida is ___
All of rules that apply to our cells, apply here
DNA poly and ribosomes are similar to ours
Can’t use Ab to treat candida albican infection.
Fungi are eukaryotes • Nucleus • Membrane-bound DNA • Transcription-translation is separate • Membrane-bound organelles • Endoplasmic reticulum • Golgi • Mitochondria • Molecular biology • DNA polymerases • Ribosomes Idealized yeast cell Candida is eukaryote! All of rules that apply to our cells, apply here DNA poly and ribosomes are similar to ours Can’t use Ab to treat candida albican infection.
Yeasts have a cell wall
Yeast have a cell wall
Some yeast have a ____
Not made of __ ___or made by___ ___s as bacteria
Candida does not have a capsule,___ or ___
Only unique for its __ ___l and composition of its ____
Candida cell wall
More like insects because has___ and ___ in it
Yeasts have a cell wall Yeast have a cell wall • bacteria have a cell wall • plants have a cell wall • mammalian cells do not Some yeast have a capsule • Candida does not • Cryptococcus neoformans Not made of same components or made by same enzymes as bacteria Candida does not have a capsule, cilia or flagella Only unique for its cell wall and composition of its membrane Candida cell wall More like insects because has chitin and glucans in it
Fungal Cell Wall and Membrane
___d cell wall • ___ • ____ • ___
Cell membrane • _____* instead of cholesterol
Wall and Membrane common targets for anti-fungal drugs
• Most target the ___ though
Fungal Cell Wall and Membrane Rigid cell wall • glucans • mannoproteins • chitin Cell membrane • ergosterol* instead of cholesterol Wall and Membrane common targets for anti-fungal drugs • Most target the membrane though
Common Anti-fungals
Amphotericin B • Binds to _____ in fungal membranes • Disrupts membrane____ • Given by___ for systemic infections ▪____ tolerated (Ampho-terrible) • Given as____ for topical treatment • Use topically or via IV For really bad infections, do IV in hospital • AKA aphoterrible bc it can cross react with our proteins→ make you feel awful • Lozenge: drop that they can put in there mouth that they can suck on for oral infections
Nystatin* • Binds to ____ in fungal membranes • Applied t____y as ____t or __ ___
* Oral suspension: Liquid that they swish
• Fluconazole and Miconazole* • Inhibits ___ ___ • Applied ____y as an ___ ___/___* or oral ____ • Fluconazole can also be given ____ by ____
Common Anti-fungals Amphotericin B • Binds to ergosterol in fungal membranes • Disrupts membrane structure • Given by IV for systemic infections ▪ Poorly tolerated (Ampho-terrible) • Given as lozenge for topical treatment • Use topically or via IV For really bad infections, do IV in hospital • AKA aphoterrible bc it can cross react with our proteins→ make you feel awful • Lozenge: drop that they can put in there mouth that they can suck on for oral infections Nystatin* • Binds to ergosterol in fungal membranes • Applied topically as ointment or oral suspension* Oral suspension: Liquid that they swish • Fluconazole and Miconazole* • Inhibits ergosterol synthesis • Applied topically as an oral gel/cream* or oral suspension • Fluconazole can also be given systemically by tablet
Fungal Morphology
Fungi may exist in two morphologic forms
▪ Mass of hyphae is a ____
▪ ___
▪ Dimorphic fungi can exist in ____morphology
Candida albicans is ___
Bakers yeast- Saccharomyces
Candida is interesting bc technically we consider a yeast. o Typical round cell with nucleus o Unicellular o ____ than bacteria
Sometimes you can have branched fillaments called hyphae. Candida mainly grows as ____ but can from hyphae Called dimorphic When in yeast form, it’s a bett___ ____r an____
Hyphal form→ more ____
Fungal Morphology Fungi may exist in two morphologic forms • Unicellular—yeasts • Multicellular—develop elongated branched filaments called hyphae ▪ Mass of hyphae is a mycelium ▪ Molds ▪ Dimorphic fungi can exist in either morphology Candida albicans is dimorphic Bakers yeast- Saccharomyces Candida is interesting bc technically we consider a yeast. o Typical round cell with nucleus o Unicellular o Bigger than bacteria Sometimes you can have branched fillaments called hyphae. Candida mainly grows as yeast but can from hyphae Called dimorphic When in yeast form, it’s a better biofilm former and colonizer Hyphal form→ more pathogenic.
Types of Hyphae
Types of Hyphae • True Hyphae o Formed for sex. o Yeast can have assexual or sexual reproduction (use hyphae like pillus in bacteria) • Pseudohyphae o Looks more like a fungus. • Long branching structures o Seen when pathogenic and invading host tissue o Hyphae grow down into mucosal surfaces
Yeast vs Germ Tube vs Pseudohyphae
All of these are candida
Yeast vs Germ Tube vs Pseudohyphae All of these are candida • Buddingy yeast: clonal, asexual reprotduction • Psudohypahae: Pseudo have cell wall dividers in between the structures • Can also make spores that will spread in environ • True hyphae: form a germ tube and are one continuous cell that’s not divided up
Cell Morphology linked to reproduction, pathogenicity
Cell Morphology linked to reproduction, pathogenicity • “Budding”Yeast o Asexual division • Pseudo-hyphae o Spore-forming reproduction o Tissue invasion • Germ tubes / True Hyphae o Sexual reproduction
Candida morphology in vivo Both hyphae make it hard to be_____
Candida morphology in vivo Both hyphae make it hard to be phagocytized
Candida in the Flora
____ of host tissue by____e form
• Spread in ___ ___
Candida in the Flora • Normal flora • Commensal • Digestive tract • Skin • Vagina • Ubiquitous in humans (75%) • Opportunistic pathogens • Ecological changes not infectious disease • Host health, local conditions are key • most common fungal pathogen of humans • Multiple Candida disease states • Overgrowth of yeast form • Invasion of host tissue by hyphae form • Spread in blood stream
• At any given time, ___% of popl has candida in their flora somewhere
o At some time you may not have it and then pick it up for awhile and then it goes away.
• At any given time, 75% of popl has candida in their flora somewhere o At some time you may not have it and then pick it up for awhile and then it goes away. • Changes in host make them more susceptible→ opportunistic pathogen • Most common fungal pathogen of humans because so many of us have it in our flora. • Can cause disease in a variety of ways o Yeast form overgrowth o Invasion of tissue in hyphal form. Try to grown down and cause local infection o Get into blood stream and cause systemic yeast infectionà SERIOUS. Hospital IV. Means they have some major health issue. Normally body can defend against Candida
Candida Virulence Factors
Candida Virulence Factors • Proteases (at least 12 aspartyl-type proteases) ▪ Proteases can break down SIgA. • Lipases (several) • Produces variety of lipases. • Break down cell membranes of host cells and destroy host cells • Adhesion factors (20+ cell surface adhesins) ▪ Has to stick to oral surfacesà Makes adhesins ▪ Ability to stick is important. Don’t want to be swallowed ▪ • Biofilm formation ▪ Good at forming biofilms. • Morphogenesis ▪ Yeast form vs Hyphal form ▪ Hyphal forms are tissue invasive ▪ Dimorphic change results in diff Ag on the surface. Immune sys may be generated to yeast form but not recognize hyphal ▪ Hyphal hard to phagocytize ▪ Hyphae produce more lipase than yeast→ lets it grown down into the tissue • Can bind complement but not be lysed. This hides Ag. Masking effect.
Switching morphology changes Pathogenicity Expression
Adaptability to survive in ____ anatomic sites
Switching of gene expression dictated by ___ ___.
Presence or absence of ____
Yeast are sensitive to presence or bacteria.
Some bact make them stay in yeast form
• ___ Yeast break down glucose so high sugar diet can lead to___ ___
____ contents:
Quantity and quality Saliva works against yeast. Wash away. Delivers antimicrobials
Switch from yeast to hyphae forms
Hyphae are associated with increase in ___/)____ expression, and result in ___ ___
Switching morphology changes Pathogenicity Expression Adaptability to survive in diverse anatomic sites Switching of gene expression dictated by environmental changes • Presence or absence of bacteria Yeast are sensitive to presence or bacteria. Some bact make them stay in yeast form • Diet Yeast break down glucose so high sugar diet can lead to yeast overgrowth • Saliva contents: Quantity and quality Saliva works against yeast. Wash away. Delivers antimicrobials Switch from yeast to hyphae forms Hyphae are associated with increase in protease/lipase expression, and result in tissue invasion.
C. albicans Biofilms
C. albicans forms biofilms with ___ ___
Cooperative behavior
s • __ ___ With oral Strep
___ production Contributes to biofilm slime. Allows bacteria to colonize
C. albicans Biofilms C. albicans forms biofilms with oral bacteria Cooperative behaviors • Co-aggregation With oral Strep • Environment modification→ Uses up O2 • Food web • Quorum sensing Produce Farnesol. High Farnseol will form hyphae Bw yeast and S. Gordonni. Will tell Candida to stop forming farnesol so Candida will stay as a yeast • EPS production Contributes to biofilm slime. Allows bacteria to colonize
Some oral Strep suppress pseudo-hyphae formation (____) while others stimulate formation (__ ___). S. Oralis encourages hyphae! Opp of S.gordonii.
Some oral Strep suppress pseudo-hyphae formation (S. gordonii) while others stimulate formation (S. oralis). S. Oralis encourages hyphae! Opp of S.gordonii.
A Versatile Opportunistic Pathogen
• Oral ____
____
____
____
____
____
____ rash
____ foot
A Versatile Opportunistic Pathogen • Oral candidiasis Vaginitis Onchomycosis Esophagitis Endocarditis Keratitis Diaper rash Athlete’s foot
Oral Candidiasis
___ ___s • Thrush
____ ____s • Denture stomatitis • HIV related
___ ___is • Corners of the mouth
___ ___ ____is • candidal leukoplakia
____ ____ ____
Oral Candidiasis Pseudomembranous candidiasis • Thrush Erythematous candidiasis • Denture stomatitis • HIV related Angular cheilitis • Corners of the mouth Chronic hyperplastic candidiasis • candidal leukoplakia Chronic mucocutaneous candidiasis
Host factors in the Oral Cavity
All these oral manifestations have corresponding __ ___ bc candida is commensal
Host factors in the Oral Cavity All these oral manifestations have corresponding host factor bc candida is commensal