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2 Types of Parasites
Multicellular (helmiths) and Unicellular (protozoan)
3 Most Common Helmith Infections
Ascariasis (4.2 B at risk), Trichuris (3.2 B at risk), Hookworm (3.2 B at risk)
3 Most Common Protozoan Infections
Malaria, Leishmaniasis, Trypanosomiasis
Treatments for Helmith Infection
Ivermectin and Benziomidazoles to paralyze adults, does not kill eggs
Non-Soil Affiliated Helmiths
Lymphatic Filariasis, Schistosomiasis, and Onchocerciasis
DALY
Disability Adjusted Life Years, amount of healthy years lost due to infection
Plasmodium
Parasite responsible for malaria; forms merozoites in liver that infect red blood cells.Infected RBCs form clots.
Transmitted by mosquito.
Trypanosome Brucei
Causes African Sleeping Sickness, transmitted by Tstete Fly, and affects the central nervous system. Grows in lymph, blood, and spinal fluid.
Endemic to Africa
Trypanosome Cruzi
Causes Chagas Disease, transmitted by Triatomine, and infects muscles. Grows in mastigote cells before bursting out into the blood. Eventually causes heart attack.
Endemic to South America
Leishmania Major and Donovani
Responsible for Cutaneous (Leishmania Major) and Visceral (Leishmania Donovani) leishmaniasis; transmitted by sandflies.
Wuscheria bancroft
Causes lymphatic filariasias (elephantism) by blocking lymph. Mosquito transmitted.
Treatment for Visceral Leishmaniasis
Ambisome, treats in one day
Ascaris Life Cycle
Grows in soil, enters through contaminated food/water, both intestine→lungs→small intestine
Hookworm Life Cycle
Eggs in soil grow into larvae, enter through skin→lungs→small intestine
Wucheria bancroft Life Cycle
Not soil associated, transmitted by mosquitoes. Enters skin→lymph system. Produces microfilaria in to be taken up by mosquitos.
Plasmodium Life Cycle
Mosquito bites, injects sporozoites into skin→blood→liver. At liver, sporozoites turn into merozoites that infect red blood cells. Some merozoites sexually reproduce to make gametocytes.
Trypanosome Brucei Life Cycle
Replicates in spinal fluid/blood and in Tstete fly
Trypanosome Cruzi Life Cycle
Replicates in amastigotes and in Assassin bug, triatomine.
Leishmania Life Cycle
Sandflies inject flagellated promastigotes in blood→macrophages. Eventually, they burst out of macrophages as amastigotes to be taken up by sandflies
Zoosporic Fungi
primitive aquatic fungi, spread via zoospores (asexual), anchored via rhizoid structure, parasite/symbiont/saprotroph
Zygomycetous Fungi
land based, saprotroph, aseptated filamentous fungi, spread via zygospores (sexual) and/or sporangiospores (asexual)
Dikarya
Ascomcyota:
live as septated fungi or yeast, spread via ascospores (sexual) and conidia (asexual)
Basidiomycota:
live as septated filamentous fungi or yeast, spread via basidiospores (mostly sexual)
Basidiospores
Spores germinate to form septated hypae (mating types). Buller’s Drop collects spores as it rolls down gills, surface tension launches spores into convection current.
Ascomycetes spores (ascocarps)
Shotgun (apothecium), rifle (perithecium), and grenade (cleistothecium) to launch spores.
Zygomycetes spores
Spores form at tip of sporangiophore, making a sporangium. Osmotic pressure builds as the fungi grows, finally launches the spores.
Dutch Elm Disease
Mountain Pine Beetle + Blue Stain Fungi (3 species) devastate pine trees. Fungi colonize phloem, feed on sap.
Superficial Fungal Infection
Most common/benign.
Dermatophytes (Tinea)-feed on keratin (ringworm+athlete’s foot).
Candida albicans (yeast)- oral thrush, diaper dermatitis.
Invasive Fungal Infection
Rare and dangerous, normally in immunocompromised patients.
Yeast- systemic, rarely pulmonary (Candida sp.+ Cryptococcus sp.)
Molds- primary pulmonary (aspergillus fumigatis + mucorales)
Dimorphic- primary pulmonary but spreads (Histoplasma + blastomyces)
Candida albicans
yeast, morphologically switch to pseudo- and true hyphae. Can reach other organs through blood vessels.
Cryptococcus sp.
yeast, encapsulated, can infect both immunocompetent and compromised patients. Forms lesion called Cyrptococcosis. Can hijack macrophages to go to brain, causing menigitis.
Aspergillus
Mold, spores land in alveoli and invades lungs.
Invasive- mold grows all over lungs (immunocompromised).
Chronic- mold forms lesion in patients with compromised lung function
Dimorphic Fungi
environmental mycelium form → infecting yeast form. Blastomyces dermatiditis and Valley fever (Coccidioides). Can infect immunocompetent individuals.
Angel of Death (Amanita sp. and Galerina sp.)
contains heat-stable amatoxins, responsible for almost all mushroom poisoning deaths, inhibits RNA poly II
Psilocybin and Psilocin
magic mushrooms, contains agonist to corticol serotonin 5-HT2a receptor, used by Aztecs.
Echinocandins
Fungal cell wall inhibitor, fungicidal in yeast but only fungistatic in mold
Polyenes
Binds to ergesterol, forms ion channels in membrane. Fungicidal in both yeast and mold. High similarity to human cholesterol, so very toxic.
Azoles
Inhibits ergesterol synthesis, fungicidal in mold but fungistatic in yeast.
Effect of Global Warming on Fungi
Increases range, promotes fungi to increase their growing temps.
Mycorrhizal Fungi
symbiotic relationship with plants (80% of plants), most common interactions are arbuscular and ectomycorrhizae. Fungi secrete glomalin (improves soil) and stimulate plant’s immune system.
White Nose Syndrome
P. destructans (ascomcyota) infects bats. Only prevalent in US due to mycovirus. Kills 70%-100% of bats in infected cave.
Fusarium (Wilt and Oxyporium)
Wilt- Drove old banana “Big Mike” to extinction
Oxyporium- Drove Cavendish banana to extinction
Virus
Obligate intracellular parasite with DNA/RNA genome, protein capsid (capsomeres), and possibly phospholipid envelope.
Virion
Extracellular viral particle
Helical Capsid Virus
Spiral/rod shaped, length determined by nucleic acid length, can only package ssRNA
ex. tobacco mosaic virus and ebola
Icosahedral Capsid Virus
Spherical and rigid, packages all genome types, made of identical triangular proteins (most efficient)
ex. most animal viruses, HPV, polio
Complex Viruses
bacteriophages and the pox virus
Enveloped Viruses
Acquire envelope from host during replication/release (budding). Envelope helps with host recognition, provides protection from immune system. Delivers virus via endocytosis or membrane fusion.
Hershey-Chase Experiment
1952, proof DNA is genetic material using bacteriophage T2 and radioactive phosphorus.
Fraenkel-Conrat Experiment
used hybrid viruses to prove that RNA is the genetic material of the tobacco mosaic virus
Giant Virus
Mimivirus, ~1000 genes and 400nm large, able to be co-infected with microvirus
ICTV Classification
Order name: -virales
Family name: -viridae
Genus name: -virus
Class 1 virus
dsDNA
Transcription: uses host RNA polymerase
Replication: uses host machinery
ex. herpesvirus
Class 2 virus
(+) ssDNA
transcription: uses host machinery (RNA poly)
replication: circular genome uses dsDNA intermediate, needs host DNA poly
ex. parvoviruses
Class 3 virus
dsRNA
transcription + translation: uses carried RNA Dependent RNA Polymerase (RdRP)
ex. rotovirus
Class 4 virus
(+)ssRNA
transcription: uses host machinery
translation: encodes for RdRP so (-)ssRNA can be made for template
ex. Hep C
Class 5 virus
(-)ssRNA
transcription and translation: must carry RdRP to make mRNA and to make template
ex. influenza
Class 6 virus
ssRNA w/ Reverse Transcriptase (RT)
must carry RT and integrase to insert into host genome
transcription and translation: uses host machinery for both
ex. HIV
Class 7 virus
DNA w/ RT
uses cellular repair mechanism to convert gapped DNA into fully dsDNA
transcription: dsDNA transcribed into mRNA in nucleus
replication: uses ssRNA intermediate as template for viral reverse transcriptase
ex. pararetrovirus
What classes use viral RdRP?
Classes 3, 4, and 5
Infectious Cycle
Early Phase: attachment/absorption→entry/penetration→ uncoating→ biosynthesis
Late Phase:
biosynthesis→assembly→release
Early vs. Late Protein
Early protein: RdRP
Late protein: capsomere
2 Cycles of Bacteriophage
Lytic Cycle: ends w/ cell death and lysis
Lysogenic Cycle: host remains alive, phage DNA is incorporated
Requirements for Successful Infection
enough virus
susceptible and permissive cells
local antiviral defence absent or overcome
Types of Tropism
Cellular- only replicates in one cell type
Tissue- only replicates in one tissue type
Host- only replicates in one species
3 Types of media for viruses
mature organisms, eggs, and cultured cells
Embyronated Egg
sterile, inexpensive, widely used for growing and isolating viruses, used in vaccines
Mature animals
rats, mice, and guinea pigs
tabacco
Plaque Assay
Culturing viruses in bacteria. Bacteriophages and bacteria are mixed, and the phages lyse the bacteria to make plaques. Plaques can be counted to allow an estimation of phage numbers.
Cell Culturing
Less expensive than mature organisms, sterile and easy to work with. Cells can be primary (derived from tissue) or transformed (cancerous).
Cytopathic Effect
Changes in morphology due to virus infection.
ex. death, swelling, fusion forming syncytia, and changes in inclusion bodies.
Multiplicity of Infection (MOI)
average number of viral particles added per cell, modelled by Poisoon Distribution
Oncogenic Viruses
Viruses may carry oncogene copies, oncogene promoters, or interfere with tumor repressors. All are due to integration with host DNA.
DNA Oncogenic Viruses
Epstein-Barr (dsDNA)
Hep B (dsDNA + RT)
HPV (dsDNA)
RNA Oncogenic Virus
Human Leukemia Viruses (HTLV 1+2)
Some retroviridae
Oncolytic Virus
Virus that infects and lyses cancer cells
mRNA Vaccines
mRNA encoding antigen of choice encased in lipid nanoparticle. Preps the immune system to recognize and eliminate antigen + virus.
Influenza
(-)ssRNA, segmented genome, helical capsid, enveloped w/ glycoproteins (hemagglutinin and neuraminidase)
Very plastic genome = lots of mutations
Pathogenesis of Bacterial Disease
Maintain a reservoir
Be transported to host
Adhere, colonize, and/or invade host
Multiply or complete life cycle
Evade host defense
Leave host to enter new host/reservoir
Direct Contact
droplets, kissing, sex, sneezing, etc.
Indirect Contact
airborne, vehicle borne, vector borne
Virulence Factors
adhesins
capsules (slimy layer around cell wall)
nutrient acquisition systems (siderophosphates - scavenge iron)
virulence-associated secretion systems
toxins
Virulence Associated Secretion Systems
many different types, but
Type III (T3SS) spans bacterial and host membrane
uses molecular syringe w/ varying proteins
encoded by ~20 genes and present in gram-
Endotoxin
Part of the bacterial cell, such as the LPS of gram - bacteria, released by lysis or reproduction, and heat stable
Exotoxin
Secreted toxin, easily heat inactivated and can be treated with an antitoxin.
ex. botulinum toxin
Exotoxin Categories
AB
Membrane disrupting
Superantigens
Categorized by site of action (i.e. neurotoxin)
AB exotoxin
A subunit has enzymatic activity
B subunit mediates cell binding
Intoxication
Disease from pre-formed toxin w/ very fast onset
Enterohemoryhagic E. coli (EHEC)
severe E. coli poisoning, can cause hemolytic uremic syndrome (HUS) in 20% of patients
Due to T3SS injecting Tir and Shiga toxin.
May cause chronic renal and/or neurological syndromes, cannot be treated with antibiotics
What percentage of cells in the body are human?
50%
Holobiome
human genome and microbiome
Methods to Study Human Microbiome
16S rDNA sequencing
Deep genomic sequencing
mRNA sequencing
Metabolomics
16S rDNA
phylogenetic marker found in all bacteria that contains identical and variable sequences unique to certain bacteria
Metagenomics
Sequences all genomic DNA in sample, filters out human sequences, and matches bacterial sequences.
PCA/PCOA plot
Most common microbiota plot graph.
Closer dots are more alike species of bacteria.
Most common skin bacteria
Staphylococci, streptococci, diptheriods
Most common nose bacteria
Staphylococci, streptococci
Most common mouth/oral bacteria
no teeth - aerobes
teeth - mostly anaerobes
Most common urogenital tract bacteria
vagina- lactobacillus
penis- psuedomonadaceae and oxolobactericaea
2 main phyla in Gastrointestinal tract
Bacteroidetes and Firmicutes
Axenic Mice
sterile, lab made mice treated with antibiotics and delivered via C- section