Microbiology Module 5 + 6
Campylobacter
Under or uncooked poultry (half of sold poultry!) < 10 ingested cells can cause illness (low #) Symptoms arise in 2-5 days
why must group 1 viruses enter the host nucleus
became that's where the RNA polymerase is located and they are going to rely on the host RNA polymerase in order to transcribe their messenger RNAS The nucleus also contains the host DNA DEPENDENT RNA POLYMERASE Which synthesizes DNA from a DNA template—-> this is the enzyme that host cells normally use to replicate their own DNA
developmental phase of microbiome
birth to 14 months
Propagation of an epidemic is related to
the total number of susceptible individuals.
Molecular Koch's Postulates
used to prove a gene encodes a virulence factor. 1. The virulence factor is found in virulent strains of the organism but not in avirulent strains. 2. Mutating the virulence gene should reduce the virulence of the pathogen. 3. Adding the virulence gene to a non-pathogenic strain should make it virulent.
HA
viral protein hemagglutinin, plays a role in viral entry (Influenza)
How many different proteins are made from the 8 RNA segments of the influenza genome?
10
Mutualism
A relationship between two species in which both species benefit
The influenza M2 channel is the target of
Amantadine
Mimivirus
An extremely large double-stranded DNA virus
The genetic material of DNA viruses resembles the genetic material of their host cells
As a result, replication of the viral genome and transcription of viral genes occurs similar to how they do in host cells
epidemic
Defines the disease that has an incidence of larger than the expected number of cases in a short amount of time within a geographic region
Infection after exposure is influenced by
Genetics (host and pathogen) • Risk factors (age, medication, presence of other disease) • Prior exposure (including vaccination)
Influenza attachment protein
HA
Sialic acid attached to galactose provides a recognition site for which of the following?
HA
cellular tropism
HIV normally infects macrophages but not neurons
The goal of vaccination is to achieve
Herd Immunity
The rise in immune-related disorders may be explained by the
Hygiene hypothesis
Immunopathogenesis
Immune response to an infection inadvertently damages the host to such a degree that it causes illness or even death
How did SARS CoV2 become a pandemic?
Wuhan, the epicenter of COVID-19, made containment challenging. Early super-spreader events The transmissibility is higher. The infectious period & clinical spectrum are different.
Variation in host receptors within a species results in
difference in susceptibility for viral infection
assymetrical capsid
less well defined
What determines the shape of influenza
matrix protein called M1
Vaccines may be composed of
whole cells or virions that are dead or inactivated.
Super-antigens: toxic shock syndrome
S. aureus over-multiply and produce toxin
Purposes of food fermentation:
- Preservation: by limiting microbial growth - To improve digestibility - To add nutrients and flavor molecules
Group 1 viruses
-dsDNA -uses its own or host DNA polymerases for replication -dsDNA genome where DNA serves as a template for the synthesis of mRNA
Adenovirus classification
1 -dsDNA virus -Naked -Transmitted via respiratory droplets and fecal-oral Typical Group 1 DNA viruses use host DNA and RNA polymerases
Milk spoils through a succession of microbial growth.
1. Acid production by Lactobacillus fermentation 2. Yeasts and molds degrade the lactic acid 3. Protein-digesting bacteria (putrefaction) - cadaverine, putrescine
Transitional phase of microbiome
15-30 months The overall diversity goes down as particular species take control and outcompete other species
Commensalism
A relationship between two organisms in which one organism benefits and the other is unaffected
Viral tropism in influenza is based on
HA allele and host receptor type.
positive sense DNA
If a DNA sequence directly gives the same mRNA sequence from the transcription, it is known as positive sense or sense DNA
Different strategies to name viruses
Location, disease and physical characteristics
Germ free animal
More susceptible to pathogens Poorly developed immune system Lack key nutrients Lower cardiac output, thin intestinal walls, altered behavior, etc.
RNA vaccine downsides
RNA is rather unstable, which is why mRNA vaccines require very cold shipping and storage conditions. ◆ Once the RNA is injected into the body, it faces another challenge. ◆ Our cells have evolved elaborate defense mechanisms, intended to destroy foreign RNA. ● So to address this problem, the mRNA used in the vaccine is actually modified so that it's less susceptible to degradation. a robust immune response from an RNA vaccine requires two doses.
ethanolic fermentation
USED TO MAKE ALCOHOLIC BEVERAGES Typically yeast cells are used to make alcoholic beverages because they perform ethanolic fermentation.
What determines virulence?
Usually, pathogens can be distinguished from their avirulent counterparts by the presence of virulence factors that help them to accomplish these goals.
Enveloped virus
Viral envelope surrounds capsid, Imbedded are viral spike proteins which are important for viral attachment and entry into host cells
Pandemic
an epidemic that occurs on a worldwide scale so the only distinction between epidemic and pandemic is really just geography
The source of a pathogen can be
animate or inanimate.
Virus covering contains
capsid and envelope (not found in all viruses)
Viral genomes are coated with
capsid proteins.
Influenza has a segmented genome, with
eight separate linear strands of -ssRNA.
Koch's postulates
establish a causative relationship between a microbe and a specific disease.
Viral envelopes are acquired during
exit from host cells. The viral attachment and entry proteins imbedded in the envelope are transcribed and translated from the viral genome in the infected host cell, and they are trafficked through the endomembrane system and inserted into the host cell membrane that is destined to become the viral envelope.
Central core of virus contains
genome: DNA OR RNA some also contain addit. proteins/ enzymes needed for their rep. cycle ex) HIV has reverse transcriptase
Ebola attachment protein
glycoprotein
HIV attachment protien
gp120
Herpesvirus classification
group 1 Typical Group 1 DNA viruses use host DNA and RNA polymerases
replication of an RNA virus occurs independent of
host proteins found in the nucleus Most RNA viruses replicate in the cytoplasm of the host
zoonotic
infections passed from animal to human
Viral tropism
is the ability of a virus to infect a particular cell, tissue, or host species
The viral spike protein
is what binds to the host receptor and initiates endocytosis of the virion into the host cell.
M1
matrix protein, determines shape of influenza
Case-to-infected ratio (CI)
measures the proportion of infected people who develop disease Differs by pathogen, depends on virulence
Microbial exotoxins fall into nine categories based on their
mechanism of action.
as gut microbes digest complex carbohydrates, they produce
metabolic byproducts one class of metabolic byproducts commonly produced are short-chain fatty acids, which include ● Butyrate ● Propionate ● acetate.
intracellular obligate parasites
must have host • No organelles • No cytoplasm • No ribosomes
Spectrum of antiviral drugs
narrow each one of these drugs targets a very specific viral protein, enzyme or process that's used by a specific virus.
A virus coated with ____________________ cannot attach to host cells.
neutralizing antibodies
Food-borne infections
occur via ingestion of pathogen followed by growth in intestines.
icosahedral capsid
polyhedral with 20 identical triangular faces Each capsid protein makes up a face of the icosahedron. Many bacteriophages exhibit both
Food-borne intoxications occur when
preformed bacterial toxins are ingested DOES NOT GROW IN HOST
Alkaline fermentation
produces basic compounds instead of acidic compounds. China, Japan, or Africa, alkaline fermented foods are more common
purpose of capsid
protects genome, protein based
Viruses are composed of
protein and nucleic acid + more sometimes
Decomposition of proteins
putrefaction
Oxidation of fats
rancidity
Food spoilage
refers to the process through which microbes that are found on your food start breaking down the food and releasing metabolic by products that change the biochemistry of the food
Polymorphisms in ACE2 could possibly result in
resistance to COVID-19
Prevalence
the total number of cases in a population at a particular time Decreases with recoveries/deaths
Viral tropism is largely determined by
the viruses ability to recognize and bind to the surface of an appropriate cell Usually this attachment occurs through a very specific interaction bw the viral attachment protein present on the surface of the virus and a receptor protein present on the surface of the host cell For enveloped viruses the attachment protein is embedded within the envelope. For non enveloped viruses the attachment protein is either art of the capsid or embedded directly in the capsid
Viruses are classified based on
their genomic makeup and strategy for making mRNA.
Influenza Naming System A/Sydney/05/97/(H3N2)
virus type place isolated strain number year isolated virus subtype (alleles)
Some are mutualistic
—> they get a warm nutrient rich place to live and they provide us with some benefit for example) microbes in the gut provide you with metabolites that you need to help digest food
Toxins that disrupt the cell cycle
can stop or stimulate host cell division.
tailed capsid
complex multipart structures
Negative sense RNA virus
contains a single stranded RNA as their genetic material that produces the complementary sequence of mRNA.
Positive sense RNA virus
contains a single-stranded RNA as their genetic material that can work directly as mRNA.
Influenza HA protein binds host cell receptors to initiate
endocytosis before the virus can be taken up, the HA protein gets cut by a host protease, expressed on the host cell surface. ◆ This cut releases a hydrophobic piece of the HA protein called a fusion peptide. Now, normally endocytic vesicles in eukaryotic cells, also known as endosomes, mature into lysosomes. ◆ Lysosomes are these highly acidic compartments that digest and recycle materials that cells take up from their environment. ◆ Once the virus is taken up into an endosome, it has to escape from that endosome before it gets digested and destroyed. ◆ During the normal maturation process of an endosome to a lysosome, the endosome is acidified by proton pumps found in the endosome membrane. Protons accumulate inside the endosome and remember, there's a proton channel on the viral envelope called M2, and that allows those protons to pass across the viral envelope, so the pH also drops inside the viral particle. ● Now pH changes, alter protein structures. ● So the decrease in pH leads to a conformational change in the HA protein, and that change causes the HA protein to release from the host receptor. ● Here we can see these three circular domains of the HA protein bound to the sialic acid receptor.
Once attachment has occurred the virus can
enter the host cell and begin replicating For animal viruses there are 3 main routes for entry
The virulence of many bacterial pathogens can be linked to
exotoxins, ◆ which are proteins that are encoded by bacterial genes synthesized upon infection of a host and secreted from the bacterium to nearby host cells.
A major difference between enveloped and non-enveloped viruses is that enveloped viruses display attachment proteins on their surface while non-enveloped viruses do not.
false A non-enveloped virus will have its attachment proteins present in its capsid
Coronaviruses
family of enveloped, non- segmented +ssRNA viruses of vertebrates. coronaviruses actually contain the largest known genomes among RNA viruses.
food contamination
food contamination is different it refers specifically to food that's been contaminated with a pathogen that can make you sick
DNA viruses that cannot enter the nucleus must carry a
functional RNA polymerase so their genome can be transcribed
What process do all enveloped viruses require for naked capsid to enter the cell?
fusion of virus and host membrane
mantadine-resistant strains of influenza have developed, and this resistance occurs by
genetic changes in amino acids that line the M2 channel.
Which viral genome can be immediately translated upon entry into the host cell?
+ sense RNA
Very few antiviral agents exist.
- Antibiotics don't work because viruses don't have the structures that antibiotics target. (peptidoglycan/cell wall) - Applying the principle of selective toxicity is much harder for viruses than it is for bacteria. (viruses use host cell functions) - Viruses use host cell functions to make copies of themselves. So, few targets are unique to the virus. - If you inhibit a host cell process, toxicity will be high.
Group 4 viruses
-(+)ssRNA -requires RNA dependent RNA polymerase to make a template for mRNA and genomic replication -viruses with a +ssRNA genome who's genome is mRNA that an be recognized by host ribosomes so it can be translated directly as mRNA -you need one copy of mRNA from the host cell to generate enough viral protein to make lots of new viral particles -genome is used as a template first to make antisense RNA and then antisense RNA is used as a template to make copies of mRNA
Group 5 viruses
-(-)ssRNA -requires RNA dependent RNA polymerase to make mRNA and replicate its genome -viruses with a -ssRNA genome where the genome serves as the template for the formation of mRNA -it is the negative sense complementary molecule that an RNA dependent RNA polymerase used to build mRNA
Group 7 viruses
-dsDNA pararetrovirus -requires plant host reverse transcriptase to make dsDNA -plant viruses that have a dsDNA genome that serves as the template for the generation of more mRNA -looks like group 1 viruses but the RNA thats synthesized is used as a template to make more copies of the dsDNA genome using a host reverse transcriptase
Group 3 viruses
-dsRNA -requires RNA dependent RNA polymerase to make mRNA and genomic RNA -dsRNA virus where one of the 2 strands if the genome is mRNA and the other strand is complementary to the RNA, so upon entering a host, the strand that is complementary/anti-sense is used as a template to generate many copies of mRNA that can be translated by ribosomes
Group 6 viruses
-retrovirus -packages it's own reverse transcriptase to make dsDNA -retroviruses that have ssRNA that is first converted to dsDNA by the enzyme reverse transcriptase -the dsDNA is then integrated into the host genome and the mRNA is generated through transcription of the integrated DNA -bring in RNA and reverse transcriptase transcribes it into DNA which is then used through the process of transcription to synthesize mRNA
Group 2 viruses
-ssDNA -requires DNA polymerase to generate a complemetary strand -ssDNA genome where first steps in their replication is the synthesis if the complimentary strand of DNA to form dsDNA, which then serves as a template for the synthesis of mRNA
What are the advantages of using viral polymerase?
1) Can evolve traits that better meet the needs of its own replication. (They tend to go faster, generate genome faster) ALSO tend to have lower accuracy, more mutants = faster evolution 2) Does not need to gain access to the nucleus which is guarded by nuclear pore complexes So viruses that have to get into the nucleus must have specific strategies and often special accessory proteins that allow them to access the nucleus 3) They can infect cells that are not actively replicating In eukaryotic cells DNA polymerase is only active when cells are preparing to divide, if a cell is not in the right phase of the cell cycle and its DNA polymerase inst active then a virus isn't going to be able to replicate in that host cell
fomite
A physical inanimate object that serves to transmit an infectious agent from person to person.
Enveloped virus
A virus enclosed within a phospholipid membrane derived from its host cell.
downsides of Live Attenuated Vaccines
First, since the vaccine is composed of live cells or viral particles, storage is very critical, so it's harder to store and it's harder to transport. ○ Second, there's potential for a patient to develop signs and symptoms of disease during the mild infection that's caused by the vaccine. ○ Then finally, there is a risk of the attenuated pathogen mutating and reverting back to full virulence
Trace by-products of other fermentation pathways provide
Flavor compounds
Amantadine
The drug amantadine is a specific inhibitor of the viral M2 protein, it essentially clogs the channel and prevents protons from moving across the viral envelope. In the presence of this drug, viral RNAs remain stuck in the endosome and so replication is inhibited.
Advantages of Influenza replicating in the host nucleus
The first is that splicing happens in the nucleus, and we saw that two of the RNA segments need to be spliced in order to code for two or four different proteins. ● By replicating in the nucleus, the mRNAs can be spliced. ◆ The second advantage is that it's a nice protection mechanism. ● There are RNases in the cytoplasm of host cells that can degrade rogue RNAs, and so by entering the nucleus, the virus is protecting itself from cytoplasmic RNases. Then finally, the mRNAs that are made in the nucleus acquire a five-prime cap by stealing caps from host mRNAs in the nucleus, and that process is called cap snatching. ● Stealing a cap from a host mRNA gives the viral mRNAs a binding site for the host cell ribosome, and it means that the host cell mRNAs don't have a five-prime cap anymore, they've been stolen. ● The cell will only make influenza proteins and not use any energy to make its own proteins. ● This allows the virus to really take over the host cell.
How do we identify virulence factors?
The first step is typically a comparative genomics approach in which you compare the genomes of related virulent and avirulent pathogens. ● What you're looking for here is a gene that's present in the virulent strain and not the avirulent strain that could potentially encode a product that makes the virulent strain virulent. ● Once you've identified a gene that's present in the virulent strain and not the avirulent strain, you need to then do an experimental analysis to prove that the gene is in fact going to encode a virulence factor. ◆ Now, this can be done using a version of Koch's postulates that allows you to test the role of a potential virulence factor gene.
Segments of Influenza genome
The first three segments here code for subunits of the viral RNA-dependent RNA polymerase. ➔ Segments 4, 5, and 6 code for structural proteins, so HA, NP, and NA. ➔ Then segments 7 and 8 are unique because these are RNAs that get alternatively spliced. ➔ Segment 7 codes for both the M1 matrix protein and the M2 ion channel, and then segment 8 codes for the nuclear export proteins.
Are viruses abundant?
YES majority do not cause disease in air, surface, food water
Homolactic acid fermentation
YOGURT AND CHEESE In this route, a carbohydrate is our starting point. ◆ That carbohydrate is broken down often into glucose, which is then fed through glycolysis to produce pyruvate. ◆ Now during the fermentation process of the cells that are doing the fermentation are kept in an anaerobic environment. ◆ In the absence of oxygen, those cells will then ferment that pyruvate, and if it's a specific species that performs homolactic fermentation, the pyruvate will be fermented to lactic acid.
Is an increase in prevelence ever a good thing?
Yes! with AIDS it showed a lack in mortality
Edible fungi
multicellular fungi or mushrooms, and we've got the single-celled fungi, which are edible yeast. Edible algae
Hand sanitizer is not effective against
naked viruses
Reservoir:
natural environmental location in which the pathogen normally resides
NA
neuraminidase, key role in viral influenza exit, protein
There's a relationship between dysbiosis of the gut and
obesity obesity involves complex interactions between genes, diet, and a long-term imbalance between energy intake and expenditure. ◆ But evidence suggests the microbiome also plays a pretty important role. Early researchers found that obese humans and animals have a less diverse gut microbiome than lean humans or animals.
superantigens
over-activate and disrupt the host immune response.
mRNA vaccines
provide your body with instructions for making pathogen proteins. These mRNA vaccines co-opt your cells to produce viral antigens, essentially turning your body into its own inoculation factory.
infection
replication of pathogen in host Not everyone infected shows signs and symptoms of disease
INFLUENZA HA protein binds to_______________on host cells, and the virus is taken up by _______________
sialic acid receptors receptor-mediated endocytosis.
Some pathogens secrete proteases that cleave the proteins that hold host cells together within a tissue
so that the pathogen can get past barriers to access more host cells.
opportunistic pathogens
so they can only cause disease in an immunocompromised host.
Sporadic incidence
some diseases are only seen rarely and they're not clustered within a specific geographic region until we call them sporadic ● ex) tetanus is a sporadic disease the incidence of infection is extremely low and it only occurs every once in awhile and in Scattered locations ● now it doesn't spread from person to person and so if a single case emerges we don't see large numbers of subsequent cases occurring within that same region
Disease occurs when
some outside agents that's capable of causing a disease meets a host that is vulnerable to the agent in a given environment that allows the agent and the host to interact
Acid fermentation products
sour taste
Host cell receptors vary between .
species difference in affinity can effect tropism ex) glycosylation of DPPR for MERS CoV infection
SARS-CoV-2 attachment protein
spike
Super-antigens
stimulate helper T cells, which produce cytokines. Massive inflammation: • Fever • Sunburn-like rash • Multiple organ failure • Coma and death
Botulinum and Tetanus toxins
target vesicle trafficking in motor neurons. Both of these toxins target motor neurons, which innervate muscles to induce muscle contraction. ➔ They both target exocytosis within your neurons and so they disrupt neurotransmitter signaling. ➔ They're also both A-B toxins Botulinum toxin has an A subunit that interacts with snare proteins and inactivates them.: This is fatal because a loss of contraction of the diaphragm can lead to respiratory failure Then tetanus toxin has the opposite effect. Its target is something called synaptobrevin, which leads to excess secretion of acetylcholine and prolonged muscle contraction.
hygiene hypothesis
that exposure to microbes and certain infections, actually helps the microbiome and the immune system develop, both of which contribute to healthy states and prevent disease states.
If a pathogen has a very low LD50
that means that fewer organisms or viruses are required to kill half of the hosts in your experiment. ◆ Meaning it's more virulent because even a very small number of infectious agents can result in death.
primary pathogens
that they are able to breach the defenses of a healthy host and cause disease in a healthy host.
Some toxins disrupt signal transduction by inducing the production of second messengers
that trigger cellular changes that help the pathogen in some way.
R0
the basic reproduction number, tells us how easily an infectious disease spreads. It's a ratio of the number of new cases, to the number of existing cases.
Virulence:
the degree or severity of disease
if R_naught is greater than one,
the infection is going to be able to start spreading in that population ◆ Because every person that gets sick is ultimately going to lead to another sick person.
host tropism
the infection specificity of certain pathogens to particular hosts
Koch's Postulates
➔ First, you have to demonstrate that the microorganism is found in all organisms suffering from the disease, but that it's not found in healthy organisms. ➔ Second, you must isolate the microorganism and grow it in pure culture in the lab. ➔ Third, you must take that cultured microorganism and demonstrate that it causes disease when introduced into a healthy organism. ➔ Forth the microorganism should be reisolated from your diseased experimental host and identified as being identical to the original causative agent.
What are the advantages of using host polymerase?
1) The virsus avoids the energetic cost of manufacturing polymerases inside the host (save resources for making more copies of capside proteins and genome) BUT The repoductive potential is limited by the energy sources of the host cell. 2) DNA and RNA polymerases are centrral to cell function, that the host species is unlikely to evolove a mutant that resists the virus
Stable phase of microbiome
31-46 months Occurs when the diversity stops decreasing and the composition of the microbiome has reached a steady state that is then maintained throughout the life of the individual, except for some fluctuations that can occur due to things like geography and lifestyle (diet, drugs)
Influenza class
5, enveloped with helical capsid with a segmented genome. Its genome consists of eight molecules of antisense RNA. Each individual RNA molecule comes with a copy of RNA-dependent RNA polymerase associated with it.
Important consideration of MERS
75 percent of MERS cases had some kind of underlying disease, and so it seems like it takes a lot of virus to infect you and you have to be pretty sick to begin with to succumb to it. It's deadly if it can establish infection, but thankfully it's not very good at establishing infection.
Acetate
Acetate, on the other hand, is thought to promote obesity. ◆ It's absorbed into the blood and it travels to the liver, where it's used for lipid synthesis and storage.
negative sense DNA
If a DNA sequence produces complementary mRNA sequence from the transcription, it is known as negative sense or antisense DNA
Yogurt as edible bacteria is safe because
If you consume yogurt, you're consuming a fermented dairy product that also still contains some bacteria, although the concentration of bacteria in yogurt is pretty low and the species that are found in yogurt happen to have lower concentrations of nucleic acids and so it's safe to consume.
Virulence may be due to the host
Immunopathogenesis (collateral damage!): Immune response to an infection inadvertently damages the host to such a degree that it causes illness or even death
Incidence
Incidence is the # of new cases appearing in a population during a specific time period
Staphylococcus aureus food borne infection
Main reservoir is nasal cavities High protein foods: meat & dairy Extracellular enterotoxins Nausea, vomiting, cramps
For all RNA viruses the RNA genome presents a problem
Making copies of the genome involves synthesizing RNA From and RNA template —-> and making mRNA involves synthesizing RNA from an RNA template Host cells make DNA copies from DNA polymerase using DNA poly and all cells make RNA from DNA templates using DNA dependent RNA polymerase BUT cells DO NOT routinely make RNA from an RNA template All RNA viruses have to have a virally encoded RNA dependent RNA polymerase (an enzyme that can produce RNA from an RNA template
Salmonella
Meat, poultry, eggs >105 ingested cells for illness (a lot) Incubation time as short as 8 hours
E. coli O157:H7
Meat, unpasteurized juice, fruits, vegetables, well water ~500 ingested cells can cause illness 3-4 day incubation period Emerging pathogen (1982) - acquired gene for Shiga toxin
Which of the following parts of a virus are always found in every virus?
NA, capsid
Clostridium botulinum
Natural reservoir is soil Home-canned foods, baked potatoes in foil Botulinum toxin inhibits synaptic vesicle fusion in motor neurons Paralysis and respiratory failure (50% death rate if untreated) ** infant botulism is from germinating spores
3 main routes of viral entry
Non enveloped: The entire particle enters through receptor mediated endocytosis Following endocytosis there is a conformational change in the capsid, that allows the viral genome to enter the cytoplasm Some enveloped viruses: Mediated by the fusion of the viral envelope and the plasma membrane Other enveloped viruses ex) influenza The process begins with an interaction bw the virus and a cell surface receptor, and then after binding the virus is endocytosed. Then there is fusion of the viral envelope and the endocytic vesicles membrane and the viral genome is released into the host cell cytoplasm.
Group 5 must carry a
RNA dependent RNA polymerase
What compound provides the flavor for cheddar cheese
Really sharp cheddar has a higher concentration of that flavor compound, whereas a mild cheddar would have a smaller amount of that methanethiol. ➔ A lot of fermentation pathways involve playing around with what species you're using within the fermentation step.
What allows Sars Cov 2 to cause severe illness
SARS was found to bind to a receptor called ACE2, which is expressed on lung epithelial cells and enterocytes of the small intestine, so the cells that line your small intestine and that means that ◆ the SARS coronavirus could cause a viral pneumonia because of its ability to infect cells deep in the respiratory tract and it can also cause gastrointestinal symptoms like diarrhea because ACE2 is expressed on intestinal cells. ◆ The common cold coronaviruses use different receptors that are found in the upper respiratory tract only and so they only cause mild respiratory illness rather than viral pneumonia.
Propionic acid fermentation
SWISS CHEESE Often the second fermentation step in some cheese making this process is one in which a bacteria will take the lactic acid and ferment it to produce propionic acid, acetic acid, carbon dioxide, and water.
E. coli O157:H7 produces
Shiga toxin which cleaves rRNA, blocking protein synthesis Binds receptors on kidney and blood vessel cells • Bloody diarrhea & kidney failure his toxin is what we call an AB toxin, Binding to the receptor induces uptake by the target cell, and once inside the target cell, the A portion of the toxin cleaves ribosomal rRNA.
Spoilage molds
Spoilage Molds Break Down Tough Skins of Fruits and Vegetables Allowing Bacteria Access ➔ this type of succession also occurs when fruits and vegetables spoil ➔ most fruits and vegetables have these really nice thick skins that are made of complex carbohydrates that bacteria cannot break down ◆ but spoilage molds do you have enzymes to break down these complex carbohydrates that make up the skin
Novel Cov vs SARS
The novel CoV has a similar genome & uses the same host receptor as SARS-CoV.
Viral vector vaccines
The viral vector is an adenovirus, which is a virus that typically causes the common cold. ● But the virus used in this vaccine is a modified version of the virus, so it can enter cells but it cannot replicate inside them and it cannot cause illness.
If a plasma membrane surrounds the capsid
The virus is enveloped
killed cell or inactivated virus vaccines.
These contain whole pathogens, so either whole bacterial cells or whole viral particles that have been killed or inactivated with heat, chemicals, or radiation This class of vaccine results in a weaker immune response, and so inactivated vaccines usually require either higher doses and or multiple boosters to ensure a robust immune response.
how vaccines work.
They prime our immune system to respond faster and better when we are actually exposed to
Cholera toxin mechanism
This is also an AB toxin and it disrupts cell signaling in your intestinal cells. The binding of the toxin to host cell membrane proteins triggers endocytosis and the formation of a toxin-containing vesicle that is transported to the host endoplasmic reticulum. As a result of the toxin, adenylate cyclase becomes constantly stimulated to produce the second messenger cAMP. ○ cAMP activates various ion channels in the membrane, which leads to a major outflux of solutes into the intestinal lumen.
A virus particle is composed of
a genome, capsid, and sometimes more.
A successful virus must be able to adhere to ___________to initiate infection.
a host cell
alternative splicing
a mechanism that enables a single messenger RNA to direct the synthesis of different protein variants with different biological functions. ● Basically, these segments get cut up and spliced in different ways to produce distinct mRNAs that code for distinct proteins.
S. aureus produces
a membrane disrupting exotoxin called Alpha Toxin But the toxin is only produced when the pathogenic strain is introduced into the blood. The toxin forms a transmembrane pore ○ that associates with the plasma membranes of red blood cells, causing leakage of the cytoplasm and influx of fluid, which then leads to the cells bursting. But there are many many many different strains of staph aureus, and different strains can produce different toxins that act as virulence factors and make the strain pathogenic
Dysbiosis
a pattern of microbiota correlated with disease. For example Certain microbial compositions of the skin are associated with atopic dermatitis, acne, psoriasis, allergies, and even skin cancer. Variations in the vaginal microbiome are associated with STDs, yeast infections, and preterm birth. Variations in the lung microbiome are associated with asthma and frequent colds
spirulina,
a photosynthetic bacterium that has an extremely low concentration of nucleic acids compared to other bacteria but also has a really high percentage of vitamins and minerals. It's thought to have a really high nutritive value.
MERS binds to
a receptor called DPP4, which is expressed in lung cells but also in kidney cells, which explains the possible kidney failure associated with MERS infection.
Virus size
about 10-100nm bacteria are 1-10 microns euk 10-100 microns result: many viral particles can fit into host cell
Antigenic shift
abrupt major change that results from the reassortment of different alleles, creating totally new combinations or new subtypes. If 2 strains infect the same host, their RNA segments can reassort ex) pigs are mixing bowls
Epidemiology studies the
agents, hosts, and environments that lead to outbreaks. The triangle of epidemiology
Viruses target
all forms of life Bacteria (bacteriophages)• Eukaryotes (animals, plants, protists, fungi) • Archaea• Other viruses (satellite viruses)
Gnotobiotic animals
all microbes are known, includes germ-free used to study normal microbiota. born via c section
Tamiflu
blocks neuraminidase, preventing viral release Neuraminidase inhibitors prevent sialic acid cleavage, causing the viral particles to aggregate at the cell surface and that surface aggregation reduces the number of virus particles that are actually released and can move on to a new host cell.
why do the mRNAs in influenza have modifications
all of these messenger RNAs have a five-prime cap and a poly-A tail, those modifications are necessary because influenza infects eukaryotic cells, and eukaryotic ribosomes translate mRNAs that have a five-prime cap and a poly-A tail It's important that the viral RNAs can be recognized by host ribosomes in order to be translated.
Antibodies are proteins that circulate in the blood and recognize foreign structures called
antigens.
Based on what we've learned about diverse DNA and RNA animal viruses, which of the following is true? a Transcription of viral mRNA always takes place in the nucleus of eukaryotic cells. b Translation of mRNA for the production of viral proteins always takes place in the cytoplasm of eukaryotic cells. c Most enveloped viruses exit the host cell through cell lysis. d Most enveloped viruses enter host cells by direct fusion between the viral and host cell membrane. e All of the above are true.
b
Influenza subtypes
based on the different alleles of the two surface proteins; hemagglutinin and neuraminidase. ● There are 18 different hemagglutinin subtypes or alleles that have been discovered, and 11 different alleles of neuraminidase that had been discovered. ○ A given strain can have any one of the 18 AJ alleles and any one of the 11 NA alleles. ○ H3N2 is a way of denoting that a specific viral strain has allele number 3 of HA and allele number 2 of NA.
heterolactic fermentation
basically a combination of lactic acid fermentation and ethanol fermentation. It's this process that's used to make sauerkraut. You ferment cabbage and the production of both lactic acid and the acetic acid is what gives sauerkraut that acidic flavor.
Alkaline fermentation
bitter taste
Capsize proteins are encoded in
he viral genome and synthesized during the replication cycle They associate often spontaneously with the genome during the assembly of new virions The capsid of various viruses vary in their overall morphology
Many bacteriophages exhibit both
helical and icosahedron morphologies
Typical Group 1 DNA viruses use
host DNA and RNA polymerases. viral genes are transcribed by HOST DNA DEPENDENT DNA POLYMERASE viral genes are transcribed by HOST DNA DEPENDENT DNA POLYMERASE
Viruses use _______ to replicate
host cell machinery enzymes and ribosomes
Different viruses attach to different
host cell receptors.
Infectivity:
how easily an organism establishes infection
Viruses are able to / cannot
impact life, causes disease, have genetic info, evolve cannot: independently replicate their genome synthesize own proteins no metabolic pathways, so cannot respond to the environment or maintain homoeostasis
influenza has a host-derived envelope studied with several viral proteins, including
including hemagglutinin HA which plays a critical role during viral entry, which plays a key role during viral exit, and that's critical for un-coding the genome.
Now, some organisms and viruses never kill their hosts so you can't do a lethal dose 50 experiments if none of the hosts die. ◆ Instead, you would measure
infectious dose 50 or ID50 which is the number of cells or virions needed to cause disease symptoms in half of an experimental group of hosts.
tissue tropism
inside a host the virus may only infect certain tissues
M2
ion channel protein, critical for uncoding the genome
Case Fatality Ratio (CFR)
is equal to the mortality rate or the number of deaths, divided by the sum of all infected individuals. ◆ This includes those that recovered without being hospitalized, those that were hospitalized, and those that have died. Establishes A Comparative Measure of Virulence ➔ One of the ways that we define virulence, particularly when a new infectious disease emerges, is by calculating the case fatality ratio, or CFR, which gives us a measure of how lethal an infectious disease is, as the probability of death given infection.
Butyrate
is thought to prevent obesity because it stimulates the production of hormones that limit hunger. ◆ It also reduces the synthesis of pro-inflammatory molecules that would normally lead to increased lipid synthesis
Influenza is a really unique RNA virus because
it actually does replicate in the nucleus of host cells.
Hand sanitizer contains ethanol which kills pathogenic bacterial cells and inactivates enveloped viruses because
it pokes holes in the membranes
Filamentous (helical) capsids
long tube of protein, with genome coiled inside. The capsid proteins interact at regular intervals with the genome and also associate with each other causing the structure to twist and giving a rod shape due to symmetry
Group 4 +ssRNA viruses carry
mRNA into the cell.
Pathogenesis
the process by which pathogens produce disease
Epidemiology
the study of patterns of disease in populations.
For group 4 viruses the first step is
the synthesis of the viral RNA poly to replicate the genome and to synthesis more mRNA that can be translated For these viruses, the first thing that happens upoon entry into a host cell is the genome serves as a template for trsnlation of the viral RNA dependent RNA polymerase Once this RNA polymerase ios produce it can use the genome as a template to produce anti-sense RNA(uses positive sense RNA as a template to build the complete eatery anti sense strand) The anti sense strand is then used as a template to make more plus sense RNA (mRNA) —-> generates mRNA that can be translated to produce capsid protein (Synthesizing plus sense copies to package into more virions)
Endemic
there are some diseases that are constantly present in our population at some low incidence level and these are called endemic endemics often have predictable patterns ○ where the incidents may fluctuate ○ often times it's words to use cycling where sometimes it increases and sometimes it decreases
the only type that causes worldwide flu pandemics in humans.
type A
The coronavirus genome is translated
upon entry into host cell. the sense RNA genome then undergoes translation to synthesize key proteins, including the RNA-dependent RNA polymerase, which is labeled here as a replicase. ◆ The replicase then generates minus strands RNA, the complement of the genome, which then serves as a template to synthesize new plus-strand RNA genomes, for genome replication, ◆ and it's also used as a template for producing messenger RNAs that can then be translated to produce viral proteins.
live attenuated vaccine
uses a weakened strain of a pathogen. ● Usually through genetic manipulation, the pathogen is attenuated to decrease its virulence or decrease its ability to cause disease. ● The vaccine can establish a very mild infection that will activate the immune defenses, but it won't make you exceptionally sick because the attenuated form is not highly virulent.
earliest form of vaccination
variolation the deliberate inoculation of individuals with infectious material from smallpox victims
VECTORS
vectors are mosquitoes fleas or ticks that will take a blood meal from an infected animal (often from a reservoir animal) and then we'll go and take a blood meal from a human and inadvertently infect the human in the process
vehicle transmission
vehicles are termed Vehicles because they facilitate that indirect passage of a pathogen from one human to another ● It passes through this intermediate vehicle to get from one host to a new host
Viral genomes are
very diverse 1000-2000 bases linear or circular single molecule or segmented dsDNA ssDNA +ssRNA (sense strand translated) -ssRNA (antisense, not translated --> used as template to make mRNA dsRNA
Most antiviral agents work by inhibiting
viral DNA/RNA synthesis. The drugs themselves are nucleotide analogs that resemble nucleotides, but they lack a three-prime hydroxyl. ◆ They can be inserted into growing DNA or RNA, but once they're inserted, additional nucleotides cannot be added and so the drug inhibits elongation of the growing nucleic acids strand. These drugs are selectively toxic because viral polymerases are more prone to incorporate nucleotide analogs
Group 5 -ssRNA viruses carry
viral polymerase in with their antisense genome. The genomes of group 5 are negative sense So they enter a host and the RNA strand is complementary to viral mRNA So the genome cannot be translated right after entry into cell INSTEAD the genomic RNA must serve as template for production of mRNA BUT *** production of RNA from an RNA template requires a viral RNA dependent RNA polymerase
Atypical Group 1 DNA viruses use
viral polymerases ex) poxviruses (Smallpox) have a a ds DNA genome but their DNA replication and transcription occur entriely within the cytoplasm of the host cell**they do not enter the nucelus, which means that no host nuceler proteons are available for the virus to use. Poxviruses cannot rely on host proteins normally found in the nucelus and must instead bring in their own polymerases. In this case the viral genome will encode the proteins that are needed for genomic replication and transcription. ALSO, poxviruses have to carry a functional RNA polymerase with them so that when they enter the host cell, their genome can be transcribed SO, A virus like this will enter a host cell and deposit both the double stranded DNA genome and a functional DNA dependent RNA polymerase into the cytoplasm
naked virus
virus without an envelope
Members of the poxviridae family replicate their genome through use of
virus-encoded DNA-dependent RNA polymerase. virus-encoded DNA-dependent DNA polymerase.
bacteriophages
viruses that infect bacteria
satellite viruses
viruses that infect other viruses
toxins that form holes in host cell membranes,
which break them open and cause leakage of cell constituents.
Some toxins can stimulate the cytoskeleton
which can cause the cell membranes to change shape, and in some cases actually, wrap around the pathogen to help the organism enter the cell and access the nutrients in the cell's cytoplasm.
Some toxins disrupt protein synthesis by targeting eukaryotic ribosomes
which can then lead the cells to lyse due to apoptosis
Some toxins disrupt vesicle traffic or target exocytosis
which impacts the release of material from intracellular vesicles.
Many of the organisms in your microbiome are commensalism
which is a type of symbiosis where one organism benefits and the other derives neither benefit nor harm. —> The bacteria get a warm nutrient rich place to live and we get nothing in return But they don't harm us
The third type of vaccine is a subunit or acellular vaccine,
which is composed of isolated parts of the pathogen instead of the whole pathogen. ● These vaccines are produced either by chemically degrading a pathogen and isolating its key antigens, or by producing the antigens through genetic engineering. ● The advantage of this type of vaccine is that it cannot cause the disease state, and because it contains only the essential antigens of a pathogen and nothing else, the risk of side effects is relatively low. ● The disadvantage is that you have to identify the antigen and isolate it or manufacture it, whereas with inactivated and live attenuated vaccines, you're using the entire microorganism, and so the immune system is presented with all possible antigens at once
antigenic drift
which occurs because viral RNA polymerase is error-prone. ○ Unlike host polymerases, a viral polymerase has no proofreading ability, and so mutations happen readily. ○ Now, every time the genome is replicated, mutations can occur. ○ Many of them are silent or have negative effects on the virus's ability to replicate. ○ But sometimes nucleotide changes can lead to subtle differences in protein structure and function which can make the flu virus more effective at replicating. ○ Antigenic drift can lead to new strains that may be able to attach to host cells better or replicate faster or exit host cells better, which can lead to the emergence of a strain that may transmit better in humans or cause more severe disease.
For enveloped viruses the attachment protein is embedded ___ For non enveloped viruses the attachment protein is either ______
within the envelope. part of the capsid or embedded directly in the capsid