Lecture 10 - Mycology and Candida albicans Oral Biology

Mycology is the study of ____________

Fungi

Fungi are _______________ in the environment

Ubiquitous

What are 3 types of fungi?

- Mushroom

- Mold

- Yeast

Fungi are used frequently in __________ and ________________ applications

- Food

- Pharmacy

Some fungi are considered ____________ - but eukaryotic

Microbes

TRUE/FALSE

There are many species of fungi in the human flora

FALSE

There are few species in human flora

What type of fungi could reside on a human?

Candida albicans

Candida albicans is an example of what type of fungi?

Yeast

What are some examples of helpful fungi in food and pharmacy?

- Bakers yeast (Saccharomyces cerevisiae)

- Penicillium roquefortii

- Penicillium camenbertii

_______________ _______________ accidentally

allowed a fungus to grow on a petri dish of Staphlococci bacteria.

The fungal species was penicillium nodatum, and the secreted anti-bacterial chemical was named ________________.

- Alexander Fleming

- Penicillin

What is the end product of yeast?

Alcohol (Ethanol) (ATP and CO2)

Yeasts are _____________ (they eat dead organic matter)

Saprophytes

What species of fungi is:

- A resident of all mucosal surfaces and dental plaque

- Generally not harmful-commensal, but opportunistic

- Candidiasis

- “Thrush”

- "A fungus among us"

Candida albicans

What does Candida albicans mean?

Candida = White

Albicans = White

Are fungi eukaryotes or prokaryotes?

Eukaryotes

Fungi has similarity with __________ cells, which makes targeting difficult

Human cells

Which of the following has a cell wall (can be more than one):

- Yeast

- Bacteria

- Plants

- Mammalian cells

- Yeast have a cell wall

- Bacteria have a cell wall

- Plants have a cell wall

- Mammalian cells do not

Are the yeasts cell wall the same as bacterial and plant cell walls?

No

What 3 components make up the rigid fungal cell wall?

- Glucans

- Mannoproteins

- Chitin

What type of sterol is in the fungal cell membrane?

Ergosterol* instead of cholesterol

What two components of fungi are common targets for anti-fungal drugs?

Wall and Membrane (Ergosterol synthesis)

Why are anti-fungal drugs sometimes harsh when taken systemically?

Ergosterol-targeted drugs can sometimes target cholesterol in humans too

What common Anti-fungal is:

- Binds to ergosterol in fungal membranes

- Given by IV for systemic infections

- Poorly tolerated (Ampho-terrible)

- Given as lozenge for topical treatment*

Amphotericin B

What common Anti-fungal is:

- Binds to ergosterol in fungal membranes

- Applied topically as ointment or oral suspension*

Nystatin

What common Anti-fungal is:

- Inhibits ergosterol synthesis

- Applied topically as an oral gel/cream* or oral suspension

- _____________ can also be given systemically by tablet

Fluconazole and Miconazole

- Fluconazole

What common Anti-fungal is:

- Inhibits the synthesis of the fungal cell wall component beta-(1,3)-D-glucan

- Is administered once daily by slow intravenous infusion

- Used to treat severe infections caused by Candida spp. and Aspergillus spp.

Caspofungin (Cancidas)

What are the two morphologic forms of fungi?

- Unicellular - yeasts

- Multicellular (hyphae) - develop elongated branched filaments called hyphae

Are molds unicellular or multicellular?

Multicellular

Mass of hyphae is a _______________

Mycelium

______________ fungi can exist in either morphology

Dimorphic

TRUE/FALSE

Candida albicans is dimorphic because it can form either yeast or hyphae

TRUE

Cell Morphology is linked to _______________ and _______________

- Reproduction

- Pathogenicity

Budding Yeast would undergo what type of reproduction?

Asexual Division

Pseudo-hyphae would undergo what type of reproduction?

Spore-forming reproduction

Germ tubes / True Hyphae undergo what type of reprouduction?

Sexual reproduction

Which of the following is involved with Tissue Invasion?

"Budding" Yeast, Pseudo-hyphae, or Germ tubes / True Hyphae

Pseudo-hyphae (Digs hyphae down into the tissue surface)

Candida Morphology in vivo (Just a photo)

What are the 2 characteristics of Candida in the Normal Flora, and where can they be found?

- Commensal

- Ubiquitous in humans (75%)

- Digestive tract

- Skin

- Vagina

Candida becoming opportunistic pathogens are due to ______________ changes, not infectious disease

Ecological changes

When treating Candida in the flora, it is important to look at host health and _____________ conditions to see what caused Candida to become opportunistic

Local conditions

TRUE/FALSE

Candida is the most common fungal pathogen in humans

TRUE

What are the 3 different candida disease states?

1. Overgrowth of yeast form

2. Invasion of host tissue by hyphae form

3. Spread in blood stream

What are the virulence factors of Candida?

- Proteases (at least 12 aspartyl-type proteases)

- Lipases (several)

- Adhesion factors (20+ cell surface adhesins)

- Biofilm formation

- Morphogenesis

▪Yeast form vs Hyphae form

▪Hyphae forms are tissue-invasive

Switching morphology changes ________________ expression

Pathogenicity

Switching morphology allows for adaptability to survive in ___________ anatomic sites

Diverse

The switching of gene expression is dictated by what 3 environmental changes?

- Presence or absence of bacteria

- Diet

- Saliva contents

Candida albicans can switch from yeast to _________ forms

Yeast to hyphae

Hyphae are associated with increase in ______________ expression, and result in tissue invasion. (Breaks down membrane of host cells)

Protease/lipase

What is the biggest variable in controlling risk for candidal infection?

Stagnant moisture

Candida species are _______________ pathogens of moisture, immune suppression

Opportunistic

Candida species can cause or contribute to diseases all over the body, what are some examples?

- Oral candidiasis

- Vaginitis

- Onchomycosis

- Esophagitis

- Endocarditis

- Keratitis

- Diaper rash

- Athlete’s foot

What are 5 different examples of Oral Candidiasis?

1. Pseudomembranous candidiasis

2. Erythematous candidiasis

3. Chronic hyperplastic candidiasis

4. Angular cheilitis

5. Chronic mucocutaneous candidiasis

What oral candidiasis is associated with thrush and is white?

Pseudomembranous candidiasis

What oral candidiasis is associated with:

- Red

- Chronic atrophic - Denture stomatitis

- Acute atrophic - antibiotics, oral steroids, or HIV related

Erythematous candidiasis

What oral candidiasis is associated with:

- Candidal leukoplakia

- White

Chronic hyperplastic candidiasis

What oral candidiasis is found at the corners of the mouth?

Angular chelitis

What candidiasis is associated with a systemic mucous infection of more than one mucous surface?

Chronic mucocutaneous candidiasis

What are some host factors in the Oral Cavity? (Just a photo)

How can antibiotics result in yeast growth?

Antibiotics lowers bacterial numbers, allowing yeast to take its place

What type of oral candidiasis is associated with:

- Thrush

- Creamy-white plaques (pseudomembranes)

▪Mucosal cells

▪Yeast overgrowth with some hyphae

▪Superficial surface of epithlium

- Can occur on the surface of the tongue, soft palate, cheek, gingivae, or pharynx

- Easily wiped off to leave red areas underneath

Pseudomembranous candidiasis

____________ ____________ is a mycosis (yeast infection) caused by the fungus Candida species on the mucous membranes of the mouth. Epithelial dysplasia (disturbance in proliferation), inflammatory cells and debris are all present. It is characterized by a coating or individual patches of pseudomembranous white slough (upper red layer) that can be easily wiped away to reveal erythematous, and sometimes minimally bleeding, mucosa beneath

Oral thrush

What are common causes of Oral thrush in newborn babies and older adults?

Newborn babies

- Immature immune system

- Immature oral flora

Older adults

- Poor nutrition/excess sugar

- Local immune suppression (e.g. steroid inhaler for asthma)

- Underlying systemic disease

What is the most common form of oral candidiasis?

Erythematous candidiasis

What type of oral candidiasis is associated with:

- Red areas of varying size due to inflammation

- Any part of the oral mucosa

- Lesions painful

- On tongue may have marked de-papillation

- Invasive hyphae

Erythematous candidiasis

What type of Erythematous candidiasis is associated with:

- Denture wearers

- Denture stomatitis

- 65% of denture wearers

Chronic atropic candidiasis

What type of Erythematous candidiasis is associated with:

- HIV + infection

- After antibiotic use

- Inhaled steroids

Acute Atrophic candidiasis

What condition is characterized by:

- Candida can biofilm on synthetic material

▪Oral prosthesis

▪Medical catheters

- Poor oral hygiene

- Poor denture hygiene

- Retention of dentures in the mouth overnight

Denture stomatitis

Histopathology of rat oral mucosa in the denture stomatitis model (Just a photo)

What oral candidiasis is associated with:

- Candidal leukoplakia

- White lesions on the oral mucosa of the cheek or on the surface of the tongue

▪Smooth or Nodular

- The white patches cannot be rubbed off

- Common in middle-aged male smokers

- Often a sign for risk of cancer

Chronic hyperplastic candidosis

What type of oral candidiasis is associated with:

- Epithelium is para-keratinized and hyperplastic

- The cause of cell proliferation is unclear

- Candidal hyphae invade the parakeratinized layer

- Lesions that are untreated are at risk of becoming cancerous

- Topical antifungals

Candidal leukoplakia

What type of oral candidiasis is associated with:

- Areas of inflammation at the angles of the mouth

- Saliva trapped in mucosal folds

- May be poly-microbial with skin bacteria

▪Staphlococcus aureus

- Common in

▪ Smokers

▪ Elderly, dysphagia

▪ Patients with other forms of candidiasis (high levels of oral Candida)

▪ Immunosuppressed

Angular cheilitis

Do Immunocompetent individuals usually have oral candidiasis?

No, Immunocompetent individuals usually don’t have oral candidiasis

Treatment of Candidiasis requires correction of underlying _______ factors

Risk

________________ immune system is key for control of Candida at the mucosal surface

Innate

What is the Infectious Disease equation for Oral Candidiasis?

What risk factors to Candidiasis are related to commensal bacterial flora?

- Antibiotic usage (kills off bacterial competition)

- Infants (immature bacterial flora)

- Diabetes or high sugar intake (elevated sugar promotes Candida)

What risk factors to Candidiasis are related to saliva production?

- Steroid usage (e.g., steroid inhalers for asthmatics)

- HIV/AIDS (medication can cause dry mouth)

- Head/neck radiotherapy

- Sjogren's Syndrome

What are risk factors Candidiasis that are related to artificial surfaces?

- Dentures or Pacifier

- Binding sites for Candida, reduces salivary cleansing, mucosal abrasion

What are two antimicrobials of saliva?

Histatins and Defensins

What salivary protein is associated:

- Small, Histidine-rich peptides (24-38 amino acids)

- At least 12 in humans

- Produced in salivary glands

- Hst5 particularly effective against Candida

Histatins

What salivary protein is associated with:

- Small, Arginine-rich peptides (28-44 amino acids)

- Many different peptides (at least 5 clusters of genes)

- Produced in many cell types

(epithelial cells, granulocytes, phagocytes)

- Several types effective against Candida

Defensins

TRUE/FALSE

Fungi are common in the environment

TRUE

TRUE/FALSE

Molds and Yeast may be involved in disease

TRUE

What is the only major fungus of significance in the oral cavity?

Candida albicans

Cell structure of fungi are ___________; thus, targets for antifungals are difficult to find

Eukaryotic

Candida albicans is a _____________ in the human flora, but is also an _________________ pathogen

- Commensal

- Opportunistic

What type of cell morphology does Candida albicans have?

Dimorphic cell morphology

Candida albicans has various _______________ factors, and _______ factors in the host are key for development of disease

- Pathogenicity factors

- Risk factors

What are 4 common oral forms of candidiasis?

- Pseudomembranous

- Erythematous (including HIV- associated infection and denture-related)

- Hyperplastic

- Angular cheilitis

Treatment of fungal infections consists of correcting _________________ factors and prescribing ______________ agents

- Predisposing factors

- Antifungal agents

Repeated occurrence of candidiasis indicates ______________ health issues that need to be addressed.

Systemic health issues