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fungi structure
organelles like animal cells
not motile
cell wall is chitin and B-glucan
cell membrane with sterols (ergosterol)
fungi drug targets
chitin and b-glucan in cell wall
(not susceptible to antibiotics targeting peptidoglycan)
ergosterol in cell membrane
cell wall in fungi vs animal cells
ergosterol instead of cholesterol
*drug target
types of fungi
yeast, mold, dimorphic
yeasts vs. molds
yeast: single cells that reproduce by sexual budding
mold: multicellular, long filaments (hyphae) forming a mat (mycelium)
dimorphic fungi
form both yeasts and molds
thermally dimorphic
ambient - mild
human body temp - yeast
fungi metabolism
obligate aerobes (some facultative anaerobes & fermenters to make ethanol - no obligate anaerobes)
all required organic sources of carbon (like decaying matter)
where can you find fungi?
environment - usually soil
many worldwide (some specific)
Candida albicans is an exception - in normal human flora
fungi replication
asexual: genetically identical offspring from one arent - budding or binary fission
sexual: mating - sexual spores makes gametangia (n) that duplicates to zygote (2n) which differentiates to zygospore
budding
asexual replication in mosts yeast, some molds
weird version of mitosis
daughter cells unequal in size
where is Candida albicans found?
normal human flora - skin, mouth, small intestine, vagina
Unchecked growth - yeast infection (vaginitis, thrush)
dermatophyte growth of candida albicans
inhibited due to fatty acids in skin
if skin is damaged fungi invades tissue and establish itself
respiratory tract fungi
mucous membranes trap inhaled fungal spores and cells that phagocytose fungi
granola formation can wall of fungi so it doesn't spread fruther
mycotoxicosis
where toxins of fungo are ingested
amanita mushrooms
produce toxins that cause hepatotoxicity (mycotoxicosis)
calviceps purpurea
produces alkaloids (LSD) when on grains which cause ergotism - pronounced vascular and neurologic effects
aspergillus flavus
makes aflatoxins that cause liver damage and tumors (hepatic carcinoma) because it causes p53 mutations
allergies to fungi
spores from aspergillum lead to asthmatic reactions
systemic reactions to drugs made from penicillin mold
diagnosing fungal infections
direct microscopic examination
fungal cultures (inhibit bacterial growth so you can see fungus)
PCR tests
serologic tests to detect antibody in systemic mycoses
antigen latex agglutination test for cryptococcal capsular antigens (CRAG test)
complement fixation tests
CRAG test
antigen latex agglutination tests for cryptococcal capsular antigens
microscopic diagnosis of fungi
visualization of spores or hyphae with special stains (like India ink)
10% potassium hydroxide to dissolve tissue but keep alkali-resistant fungi intact (candida)
anti fungal drug targets
cell wall chitin or b-glucan synthesis
cell membrane ergosterol synthesis
disrupting cell membrane
mitotic spindles
DNA synthesis
Nikkomycin
newer anti fungal targeting cell wall chitin synthesis
echinocandins
anti fungal targeting b-glucan synthesis
azoles and terbinafine
anti fungal targeting cell membrane ergosterol synthesis
oral azaleas can decrease gonadal steroid production
terbinafine is toxic so topical use mostly (same with nystatin)
amphotericin B and nystatin
disrupts fungal cell membrane
causes renal toxicity
griseofulvin
anti fungal drug targeting griseofulvin
causes liver toxicity
flucytosine
anti fungal targeting DNA synthesis
anti fungal toxicity
toxic to our cells because of similars
which antifungals are well tolerated?
fungal cell wall b-glucan inhibitions (echinocandins) because there is no similarity to our cells
candida albicans
opportunistic pathogen that is part of normal flora
oval yeasts that can form hyphae
no vaccine
Candida albicans: virulence factors
resistant to anti fungal azoles
Candida albicans: transmission & causes
transmission: yeast already on skin, GI, and vagina; can enter blood via IVDU and IV catheters from skin; enter urinary tract via urinary catheter
causes vaginitis, thrush, diaper rash, intertrigo
Chronic mucocutaneous candidiasis (immunocompromised)
disseminated infections (lead to endocarditis, candidemia, endophthalmitiis)
Candida albicans skin invasion
warm, moist areas
itchy, painful, erythematous (beefy red) and weeping
finger nail thickening and loss (frequent dish washing)
candida auris
opportunistic pathogen in normal flora that can cause outbreaks in healthcare facility - nosocomial spread
killed with alcohol based sanitizers and bleach
no vaccine
causes infection in immunocompromised; bloodstream infections 50%; high mortality
candida auris: virulence factors
multidrug resistent to fluconazole, other azaleas, amphotericin B and some echinocandins
pan-resistant strains
what causes dermatophytoses?
dermatophyte fungi (trichophyton, epidermophytan and microsporum genera)
note: can see hyphae with 10% KOH under microscopy
what causes tinea versicolor?
malassezia
dermatophytoses tranmission
direct contact - causes "tineas"
microsporum can spread from cats and dogs
infect only superficial keratinized structures usually in warm, humid areas
no vaccine
cryptococcus neofromans
opportunistic pathogen
oval, budding yeast surrounded by wide polysaccharide capsule
cryptococcus neofromans: modes of transmission
inhalation
yeast found in soil contaminated by bird feces inhaled into lungs (bird is carrier, not infected)
causes meningitis, brain infections, pneumonia
aspergillus fumigatus
opportunistic
widely distributed; decaying vegetation
only exists as molds (conidia)
aspergillus fumigatus tranmission
inhalation of airborne conidia - infect skin, eyes, ears, sinuses, other organs
no vax
causes fungus ball and allergic bronchopolmonary asperigillosis; brain abscesses in immunocompromised
most common cause of fungal sinusitis?
aspergillus fumigatus
coccidioides
coccidioides immitis and c. posadasii
in soil and endemic in southwest US and latin America
very light arthrospores carried by wind
transmitted when inhaled, infect lungs causing infection
histoplasmosis capsulatum
opportunistic
dimorphic fungi (mold in soil; yeast in tissue)
endemic in central and eastern US
inhalation of spores; in soil contaminated by bird feces
bats can infect and excrete into guano
histoplasmosis capsulatum: virulence factors
survive phagolysosome by producing alkaline substances like bicarbonate ammonia to inactivate enzymes
histoplasmosis
causes lung infection and dissemination infections
erythema nodosum: sign that cell-mediated immunity is active and infection can be controlled
mostly asymptomatic
blastomyces dermatitidis
soil, endemic mainly in north america
dimorphic fungi
inhalation of conidia spores -> transmission
causes blastomycosis
pneumocystitis jiroveci
opportunistic pathogen
fungus classification but antifungals don't work (use TMP-SMX or anitparasitics); has aspects of protozoans - cyst appearance in tissue; cholesterol in cell membrane
inhalation transmission
no vaccine
pneumocystitis jiroveci virulence factors
major surface glycoprotein - significant antigenic variation due to gene rearrangement
causes pneumonia deadly in immunocompromised (especially AIDS)
fungal infection dissemination in general
severe - can be fatal
protista cell structure
flexible cell membrane
cyst part of life cycle can have cell wall
organelles - specialized for anaerobic respiration
cytosine - cell mouth
some don't have Golgi
contractile vacuole
in protista
maintain osmotic gradient in water
protista motility
motile or not
flagella (kinetochore), cilia, pseudopodia
types of protista
single celled protozoa
multicellular metazoan - helminths or worms
single celled protozoa
sarcodina: amebas
sporozoa: sporozoans like malaria-causing plasmodium
mastigophoran: flagellates like giardia
ciliata: ciliates like paramecium
multicellular metazoan
platylheminths: flatworms
cestoda: tapeworms
trematoda: flukes
nemathelminths: roundworms and nematodes
free living vs parasitic protista
free living live in more unstable environments
parasitic form is in stable environment
free living protista
encyst to avoid environment fluctuations
secrete thick, tough wall around themselves
quiescent state
carried by environment
lose flagella, cilia, contractile vacuole, food vacuole
excyst during favorable conditions - like in body
protista metabolism
obligate aerobes or anaerobes
protista life stages
trophozoite (larva/adult) and cyst (egg) stages
trophozoite
larva/adult stage
motile, feeding, reproducing form surrounded by flexible membrane; larval form differentiate into adult form and produces egg or cyst
cyst form
non-motile, non-metabolizing, non-reproducing
survive well,
transmission
differentiate into larval form or trophozoite
types of protista hosts
definitive - sexual cycle occurs or adult is present
intermediate - asexual cycle occurs or larva is present
transmission prevention between hosts
prevent intermediate hosts from ingesting eggs that were passed by definitive host
or
prevent reproduction of parasite in definitive host to prevent disease
parasite transmission
ingestion of contaminated food.water containing cysts
ingestion of cysts on unwashed fingers
via insect vectors such as ticks, flies or mosquitos
penetration of skin with larvae
sexually transmitted
do I need to know which species for each of these?
diagnosis of parasitic infection
microscopy (giemsa stain to look at parasite; blood smear to see infected cells)
stool test for egg or larvae presents using microscopy
can see large parasites on CT scans
PCR or ELISA for parasite antigens or immunofluorescence
eosinophilia and elevated IgE
parasite prevention
insect repellents, protective clothing, modify environment, cooking properly, water treatment and filtration, good hand hygiene
chemoprophylaxis to prevent disease with anti-malarial drugs
parasite treatment
anti parasitic, antihelminthic, antimalarial or antiprotozoal drugs that target components of cellular metabolism or transport or block DNA or protein synthesis
paralyze metazoans and ectoparasites by messing with nerve and muscle function
surgical excision of large parasites
entamoeba histolytic
+virulence, transmission
trophozoite (1 nucleus; can ingest RBC) and cyst (4 nuclei)
tropical areas
fecal-oral route
no animal reservoir
virulence: trophozoites secrete enzymes causing local necrosis of colonic epithelium
granulomatous lesions: ameba (look like adenocarcinomas)
giardia lamblia
trophozoite & cyst stages
fecal-oral transmission
anal-oral transmission
human and mammal reservoirs
cryptosporidium hominis
sporozoites, trophozoites, merits, merozoites, microgametocytes, macrogametocytes, microgamete
fecal-oral tranmission
cattle reservoir
trichomonas vaginalis
motile trophozoite (NO cyst form)
sexual contact transmission
only sexually transmitted parasite discussed
trichomonas vaginalis
green discharge
malaria is caused by
Plasmodium: p. falciparum, p. vivid, p. ovale, p. malariae
plasmodium transmission
mosquito vector
definition host: anopheles mosquito (feeds at night)
humans are intermediate hosts
transmission across pallets, blood transfusions and IVDU
merozoites
part of Malaria life cycle
schizonts in exo-erythrocytic life cycle produce merozoites that lyse hepatocytes
erythrocytic cycle inside RBCs: merozoites -> ring shaped tophozoites
what causes malaria symptoms?
periodic release of merozoites from RBCs causing hemolytic anemia
(spleen enlargement and can get hepatomegaly also)
malaria virulence factors
p. falciparum has chloroquine resistance
babes microti
sporozoan
trophozoite stage (no cysts)
transmitted via tick vector
mammal reservoirs
humans are dead-end hosts
life cycle: sporogonic and erythrocytic
toxoplasmosis gondii: life cycle
sporozoan with 2 life cycle stages: motile trophozoite and nonmotile cyst
definitive host: domestic cat, other felines
humans/mammals are intermediate hosts
toxoplasmosis gondii - how to kill
cysts can be killed by iodine or boiling and removed by filtration (chlorination does not kill it)
toxoplasmosis gondii: modes of transmission
ingestion of cysts
transplacental transmission of trophozoites from infected mother to fetus
definitive host: cat
cat ingests cyst containing bradyzoites from raw meat (mice)
bradyzoites infect mucosal cells in small intestine -> male and female gametocytes which fuse to form oocysts and are excreted in cat feces
humans and mammals intermediate hosts (ingest undercooked meat; liter box cleaning .... more info on this - check LOs
more on toxo
brain eating amoebas
acanthamoeba castellani; naegleria fowleri
free living in warm freshwater lakes and soil
trophozoite and cyst stages (cysts not killed by chlorine)
brain eating amoebas: acanthamoeba castellani; naegleria fowleri - transmission
acanthamoeba enters skin or eyes due to trauma
naegleria enters body through mucous membranes while swimming - penetrates nasal mucosa and cribriform plate to enter brain (often children)
causes meningoencephalitis
taenia
helminths
t. solium -> taeniasis and cysticercosis
t. saginata -> taeniasis
flat or tapeworms - rounded head, flat segmented body
eggs excreted in feces and ingested by intermediate hosts (t. saginata cattle; t. sodium pigs)
taenia virulence factors
scolex attaches to intestinal wall with suckers hooks or sucking grooves
taenia hosts
humans are definitive hosts that ingest larvae/cysticerci in undercooked meat
cysticerci attach to small intestine wall via scolex -> adult worms
eggs passed into feces - accidentally eaten by pigs or cows
eggs in intestine burrow into blood vessels and skeletal muscle
schistosom
helminth
blood flukes - s. mansion, japonica, haematobium
separate sexes live attached to each other - female goes into male schist/groove
schistosom - transmission
penetration of skin by free swimming cercariae
intermediate host - snail (asexual cycle)
eggs excreted by definitive host hatch in fresh water
cercariae released by snails in fresh water penetrate human skin (definitive host of sexual cycle)
schistosom virulence factors
surface gets coated with host antigen so immune system cannot recognize them as foreign
pinworms: enterobius vermicularis
nematodes or round worms with complete digestive tract (females are large; male has coiled tail)
2 larval forms: rhabditiform are noninfectious and feeding while filariform are infectious
pinworms tranmission & virulence
ingestion of eggs
body covered in noncellular highly resistant coating or cuticle
lice
arthropod insects with chitinous exoskeleton
pedicures humans - elongated; infect hair
phthirus pubis - crab looking; causes crabs
nits: eggs
lice transmission
via fomites or direct contact
head lice: hats, combs, towels
body lice: clothing or personal contact - leave clothing when they need blood meals
pubic: sexual contact
lice virulence
resistance to permethrin is increasing
bedbugs
arthropod insects
cimix lectularius
transmitted via contact with bedding