Exam 4 Flashcards
Virus Shape: Helical
Nucleic acid within a hollow, cylindrical capsid made of capsomeres
Spring-looking
Virus Shape: Polyhedral
Many-sided, often icosahedral (20 triangular faces)
Virus Shape: Complex
Lack symmetry
Ex. bacteriophage
Prions
Misfolded proteins that cause host proteins to also misfold
Short for proteinaceous infectious particles
Have no genome involved; just a protein –> simpler infectious agent than a virus
Responsible for Mad Cow Disease and other neurological diseases
Prion diseases are genetic or acquired from the outside
We’ve only known about viruses for ~____ years
100
Tissue tropism
Even within a single host, a virus can only infect certain tissues
The virus has viral proteins that recognize receptors that are displayed on certain cells
Cellular tropism
Ex. a virus can infect a macrophage that has receptors, neurons don’t express those receptors so HIV can’t infect them
Virion
A complete, fully developed, infectious viral particle, found outside a host cell
Composed of nucleic acid surrounded by a protein coat
Capsid
Protein coat that surrounds a virus’s genome
Present in all viruses
Viruses require a ___ ___ for replication
host cell
Can’t be cultured in media like bacteria
Latent Viruses
Viruses that lay dormant in a host for an extended period of time
Virus still present, but doesn’t cause symptoms
Examples: Herpes simplexvirus (cold sores), Varicella virus (chicken pox, shingles, latent in nerve cells)
Viral genomes also vary in these ways (aside from DNA/RNA, single/double stranded)
Circular vs linear
Segmented (little fragments) vs non-segmented (one continuous piece)
Genome size – 1000’s to 250,000 nucleotides (smaller virus → smaller genome)
Envelope
Lipid bilayer that covers the capsid
Only found in some viruses
Formed from plasma membrane when a virus exits a host cell
Not made by the virus, just a part of the host cell’s membrane
Many viruses lack an envelop → naked (or nonenveloped)
Enveloped viruses are more susceptible to alcohol
Hand sanitizer helps tamper spread of infection;
COVID virus has envelope → alcohol dissolves spike proteins + envelope → no longer able to bind to host cell receptor
Lytic Cycle: Steps
- Attachment – phage attaches by the tail fibers to a receptor of the bacterial cell
- Penetration – DNA (genome) is injected into the bacterial cell; only the genome gets injected, not the whole phage
- Biosynthesis – production of phage DNA and proteins
- Maturation – assembly of phage particles
- Release – phage lyse the bacterial cell and release into the environment
Some RNA viruses are retroviruses, meaning…
They have an RNA genome they convert into a DNA version so that it can integrate into the host cell genome (ex.HIV)
Opposite of central dogma
Requires an enzyme that reads RNA and synthesizes DNA - Host cells do not have such an enzyme – cells never have to synthesize DNA from an RNA template
Retrovirus encode their own RNA-dependent DNA polymerase → reverse transcriptase (RT)
Lysogenic Cycle
Phage genome integrates/recombines into the bacterial genome → Prophage
Passed down as the bacterial cell divides (vertical)
At any given time, for a cell that contains a prophage, the prophage can excise itself and transition back into the lytic cycle
Temperate phage
Can choose between lytic and lysogenic cycles
Temperate phage and prophage are the same phage; depends on decision it makes
Life Cycle of Animal Viruses: Steps
- Attachment
- Entry
- Uncoating
- Biosynthesis
- Maturation
- Release
Attachment step in Life Cycle of Animal Viruses
virus binds to receptor on host cell
Entry step in Life Cycle of Animal Viruses
Virus enters host cell
Can occur through injection, receptor-mediated endocytosis (engulfed by host cell), fusion (only occurs for enveloped viruses)
Only uses one of these 3 routes
Fusion mode of entry in animal virus life cycle
Envelope (lipid bilayer) and membrane of host cell fuse
Only occurs for enveloped viruses
Uncoating step in Life Cycle of Animal Viruses
loss of capsid, releases nucleic acid into host cell
Biosynthesis step in Life Cycle of Animal Viruses
Production of nucleic acid and proteins
Process depends on Baltimore classification; If virus has DNA genome vs RNA genome
Important: 1. Viral genome must be replicated and 2. Viral proteins must be made
Maturation step in Life Cycle of Animal Viruses
nucleic acid and capsid proteins assemble
Release step in Life Cycle of Animal Viruses
New viral particles leaves the host cell
Can occur by rupture or budding (enveloped viruses)
Rupture/lysis: so many viruses are made that the cell bursts
Budding: new viruses made push against membrane, create bulge, keep pushing until membrane gives way and virus pops off, surrounded by the membrane.
The membrane parts now on it is the virus’ [new] envelope
Host range (tropism)
The spectrum of host cells a virus can infect
Certain viruses can infect only certain hosts, not everything out there
All organisms are susceptible to viruses [including bacteria]
Some viruses infect plants, others infect animals, others infect bacteria, etc; If they infect plants, for example, they don’t also infect animals → specificity
Within host, viruses typically only infect certain tissues/cells; Ex. COVID infects respiratory tract cells, not the liver or elsewhere
Host range is primarily determined by…
The ability of the virus to attach to the host cell and reproduce; does host produce the needed receptors or not
Attachment involves viral proteins and a receptor on the host cell
Tropism boils down to if the host cell is expressing a receptor on its surface that the virus can bind to so that it can get inside and cause an infection
Different viruses vary considerably in size
In general 20-1000 nm in length (very small)
Most are substantially smaller than bacteria
Some are roughly the same size as bacteria; these giant viruses are susceptible to smaller viruses (virophages)
Giant viruses can get infected by virophages
A prion is NOT a virus
All viruses have a nucleic acid genome
Some viruses have a DNA genome, other viruses have an RNA genome
Some viruses have a single-stranded genome, others have a double-stranded genome
These differences help us classify viruses → Baltimore classification system
Spike proteins
Project from the envelope of a virus
Spikes often bind receptors on the host cell
Bacteriophage (phage)
Virus that infects bacteria
Grown on media containing bacterial cells
Form plaques
Have been studied extensively as a model of virus replication; undergo lytic or lysogenic cycle
Lytic Life Cycle
When a bacteriophage docks on a cells surface, injects its genome, and converts the bacterial cell into a phage-producing factory
Results in lysis of the bacterial cell
Some viruses can cause persistent (or chronic) infections
number of virions gradually increases over time
Acute virus
A short-lived infection that resolves quickly
Viruses were initially distinguished from other infectious agents because they’re….
Small and obligate intracellular microbes
Obligates intracellular → viruses cannot reproduce on their own, need host cell to get into - however, some bacteria fit this description as well (e.g. Rickettsia)
We now distinguish viruses from cellular life forms based on their structure
Contain a single type of nucleic acid (DNA or RNA); cells have both, viruses have one or the other
Contain a protein coat (capsid)
Multiply within host cells using host machinery
Responsible for synthesis of structures that transfer viral nucleic acid to other cells; must exist host cell and infect new cells
Viruses can be grown in cell cultures
Plant/animals cells grown/maintained in media in the lab
Cell lines can be primary or continuous
Primary cell line
Derived from tissue, survive only a few generations
Aren’t able to receive survival signals from nearly cells
Continuous cell line
Derived from cancerous cells (immortal)
Ex. HeLa cells – isolated from cervical cancer from Henrietta Lacks
Cancer cells no longer rely on survival signals to survive
Much more useful; continue to grow
Virus Discovery
The study of viruses wasn’t possible until the 20th century
1886: Tobacco Mosaic Disease could be transferred from plant to plant
1892: the causative agent of Tobacco Mosaic Disease could pass through the pores of a filter. In contrast, bacteria get trapped in the filter. Infective agent was small enough to pass → tells us the agent wasn’t bacteria
1935: Tobacco Mosaic Virus was purified, enabling the study of its structure using electron microscopy
First time scientists ever saw viruses [within e. microscope]
[Bacterial] plaques
Zones of bacterial cell lysis
Formed by phages
Phage infects a bacterial cell, replicates to high numbers, lyses the cell, infects neighboring cells, etc.
Avisible clear area within a dense layer of bacteria (“lawn”) grown on an agar plate, where bacteria have been killed by a virus (bacteriophage), creating a zone of clearing that appears as a plaque; it’s an indicator of the presence and activity of a bacteriophage on the plate.
Which of the following years is closest to when viruses (such as the Tobacco Mosaic Virus) were first discovered?
1900
The interaction between viral surface proteins and host cell receptors is often responsible for:
host tropism
Which of the following components is common to ALL viruses?
capsid
Where is a prophage found?
Integrated into the bacterial genome
Which of the following enzymes is used by an RNA virus?
Viral RNA-dependent RNA polymerase
How are prions unique compared to other infectious agents (like bacteria and viruses)?
Prions lack nucleic acids
E. coli is part of the human gut microbiota. Instead of causing disease, E. coli often outcompete pathogens for resources, thereby reducing infection. This is an example of
Microbial antagonism
Which of the following statements are TRUE? Select all that apply.
All infections are caused by pathogens, All infectious diseases are caused by pathogens, All infectious diseases are caused by pathogens
Why did Typhoid Mary doubt that she was responsible for spreading typhoid fever?
She did not exhibit signs or symptoms of disease.
Which of the following are exceptions to Koch’s postulates? Select all that apply.
In addition to causing urinary tract infections, Escherichia coli is a member normal flora of the gastrointestinal tract
Pneumonia is a disease caused by multiple infectious agents
Treponema pallidum causes syphilis but is unculturable.
Which of the following is considered a communicable disease?
Flu
The work performed by an epidemiologist is most likely to include:
Determining the frequency and distribution of a disease in a population
The ability of some microbes to alter their surface molecules and evade destruction by the host’s antibodies is called:
Antigenic variation
Quorum sensing enables bacteria to make decisions based on:
Population density
Diseases caused by eukaryotic pathogens are difficult to treat because
Their cells are structurally and functionally similar to human cells
All beta lactam antibiotics:
Contain a beta lactam ring
In lab, you identify a bacterial isolate that is antibiotic resistant. Which of the following serve as an appropriate explanation for why/how the bacterial isolate is antibiotic resistant?
Bacteria can acquire resistance genes through horizontal gene transfer
Bacteria randomly accumulate mutations while growing, and some mutations render the bacteria resistant
Some bacteria lack the components targeted by the antibiotic
Antibiotic resistance
The ability of bacteria to subvert the harmful effects of an antibiotic
3 types of resistance: Intrinsic, Acquired, Evolved
Intrinsic resistance
The bacteria lack the components targeted by the antibiotic
Cells that naturally lack a cell wall (e.g. Mycoplasma) are not affected by beta-lactam antibiotics
Acquired resistance
Resistance is acquired from other bacteria through HGT
Is inevitable (”life will find a way”)
E.g. Resistance plasmids (R plasmids) contain several antibiotic resistance genes
Evolved resistance
Mutations render the bacteria resistant
Survival of the fittest (here, the ones that can still grow in the presence of antibiotic)
Prevalence
Total number of individuals with the disease, at a given point in time
Ex. How many people were affected with COVID at WCU last Thursday
Incidence
Number of new cases of disease, over a period of time
Ex. How many people came down with the flu over the past month
Pathogen
disease-causing organism (microbial)
Infection
invasion or colonization of a host by a pathogen
Not all infections lead to disease; can be a carrier (or asymptomatic)
Typhoid Mary unknowingly transmitted typhoid fever to hundreds as a carrier of Salmonella typhi
Infectious Disease
infection leading to change from a state of health
Signs
Objective changes that can be observed and measured
Swelling, fever, paralysis
Symptoms
Subjective changes that aren’t apparent to an observer
Pain, malaise, nausea
Endemic
constantly present within a region, predictable (ex. seasonal flu, malaria)
Epidemic
Significant increase above endemic levels within a region, “outbreak”
Ex. COVID in the early months; was only in China and had huge spike
Pandemic
Epidemic across multiple continents, usually worldwide
Ex. COVID after being an epidemic + spread to other countries/continents
Reservoir
Source of a pathogen, where a pathogen resides
3 kinds: humans, animals, nonliving
Human reservoir
Include carriers (ex. Typhoid Mary)
Ex. HIV
Animals reservoir
Zoonosis – disease that spreads from animals to humans
Ex. rabies, Lyme disease
Nonliving reservoir
Soil – tetanus (C. tetani)
Water – cholera (V. cholerae)
Epidemiology
The study of how and why diseases spread in populations
Epidemiologists consider approaches for controlling a disease
John Snow
The Father of Epidemiology (~1850)
Traced the origin of a cholera outbreak back to a contaminated well in the center of London
Slowed transmission by removing the handle of the well pump, preventing access to contaminated water
Approaches for controlling a disease: Treatment
(e.g. antibiotics)
Public health organizations
Centers for Disease Control and Prevention (CDC), in the US
World Health Organization (WHO), global
Approaches for controlling a disease: Prevention
Vaccines
Reservoir, vector control
Water treatment
Food inspection
Hygiene, sanitation
Approaches for controlling a disease: Public health organizations
Centers for Disease Control and Prevention (CDC), in the US
World Health Organization (WHO), global
Pathogenicity
The ability to cause disease
Yes (pathogenic) or no (non-pathogenic)
No gray area; either yes or no
Virulence
The severity of disease (degree of pathogenicity)
E.g. highly virulent (deadly) like ebola or rabies
Virulence factor
Component of a bacterial pathogen that contributes to its ability to cause disease
Includes adhesins, toxins, extracellular enzymes, etc.
Bacterial pathogens are pathogens because they exhibit virulence traits
Quorum sensing
Bacteria’s ability to sense and respond to population density
Alter their behavior depending on how many other bacterial cells are around
If enough cells are nearby, they can work together to accomplish a complex task (e.g. biofilm)
Exotoxins (toxins)
Secreted by pathogenic bacteria to damage host tissue
3 categories (SAM): Superantigens, A-B toxins, Membrane-disrupting toxins
Membrane-disrupting toxins
Forms pores in or dissolves the cell membrane → cell dies
Superantigens
Provokes the immune system to overreact leading to host damage
Antimicrobial drugs
Chemical substances that kill or suppress the growth of microbes
A type of chemotherapy
Endotoxin
Another term for lipid A, which is part of the lipopolysaccharide (LPS) that covers the outer membrane Gram negative bacteria
Antibiotics
Antimicrobial drugs with specificity for bacteria
Doctor won’t subscribe antibiotics for a viral infection
Natural antibiotics
Those naturally produced by microbes
Can be improved upon (ex. Penicillin G)
Kirby Bauer Method
Measure a bacterium’s susceptibility/resistance to many antibiotics simultaneously
Beta-lactam antibiotics
possess a beta-lactam ring that covalently bind the active site of the transpeptidase, preventing peptides from crosslinking the peptidoglycan
Biofilms
A collection of bacteria that attach to a surface
Produced by bacterial pathogens
Held together by a matrix consisting of exopolysaccharide (EPS)
Serves as physical barrier from immune system (and antibiotics)
Steps to biofilm process
- Planktonic cells attach to surface via flagella
- Cells reproduce and form microcolonies
- Produce EPS (“glue”)
- Continues until large group made, “mature”
- Leave either because its so big that a part breaks off or the cells choose to leave to go back to planktonic state
A-B Toxins
2 components: A – active (enzyme) and B – binding (to receptor)
Bacterial cell secretes A-B toxin outside of cell
B component of A-B toxin binds to host cell → B-component binds to its receptor → induces endocytosis → host cell engulfs A-B toxin
A component cuts up intracellular signals → causes host cell to not function normally
Examples: Tetanus toxin, Anthrax toxin, Diphtheria toxin
Each interfere with different signaling systems inside host cell but use same mechanism
Toxin causes signs/symptoms
Semi-synthetic antibiotics
biologically-produced then chemically modified
Synthetic antibiotics
completely synthesized chemically
Broad spectrum
antibiotic is effective against a wide range of bacteria
Narrow spectrum
antibiotic is only effective against certain species
bactericidal antibiotics
kill bacteria
Compromised immune system → doctor should prescribe a bactericidal antibiotic
bacteriostatic antibiotic
inhibit the growth of bacteria
Transmission: Contact
Direct contact: person-to-person (ex. STDs)
Congenital: from mother to fetus/newborn
Indirect contact: via fomites (inanimate objects that harbor pathogens, ex. pen)
Droplet: produced by sneezing, coughing, etc. and travel less than 1 meter
Transmission: Vehicle
Air: aerosols, travel more than 1 meter (ex. tuberculosis)
Water: often fecal contamination (fecal-oral route)
Food: undercooked, improper storage, unsanitary conditions
Transmission: Vector
Spread by arthropods (mosquitoes, ticks, fleas)
Mechanical (passive transport, fly landing on food) or biological (part of pathogen lifecycle, malaria parasite goes through changes inside mosquito)
Emerging diseases
New diseases that are becoming more common
Often zoonotic and recently jumped the species barrier (ex. COVID affected bats then humans)
4 common mechanisms of resistance
- Alter the target: mutation prevents the antibiotic from binding its target
- Degrade the antibiotic: cleave beta lactam ring
- Modify the antibiotic: inactivate it
- Remove the antibiotic from the cell: drug efflux pumps pushes antibiotic out, can be multi-drug → resistant to multiple antibiotics
Opportunistic pathogen
A microorganism that is normally harmless to healthy people but can cause disease in certain circumstances
Under the right circumstance, some members of the normal flora can become pathogenic
May occur if the host is immunocompromised → individuals with AIDS are susceptible to infection by microbes of the normal microbiota
If the microbe gains access to another body sites → E. coli reaches the urinary tract leading to a urinary tract infection
Communicable infectious diseases
Spread from person-to-person
Chickenpox, flu, AIDS
Noncommunicable infectious diseases
Malaria (requires mosquito intermediate), tetanus, botulism (via food), anthrax
Pathogen Portals of Entry
Many pathogens have a preferred portal of entry into the host
- Mucous membranes, most common (respiratory, gastrointestinal, genitourinary)
- Skin
- Parenteral (puncture, injection, bite, cut, ex. tetanus)
Pathogens also exit the body through many of the same portals
Respiratory and gastrointestinal tract are most common
Coagulase
Enzyme that causes blood clots
Secreted by Staph. aureus to protect the bacteria from phagocytosis and other defenses
Bacteria can express kinases to dissolve clots
Bacteria produce coagulase → clot forms → bacteria produce kinase, dissolving clot and releasing bacteria
Hyaluronidase
Enzyme that breaks down connective tissue that holds epithelial cells together
Collagenase breaks down collagen → allows bacteria to enter + evade
Used to disseminate from the initial site of infection and invade further into the body
Fleming’s Discovery of Penicillin
The first antibiotic was discovered in 1928 by Alexander Fleming
Fleming was studying the bacterium S.aureus and noticed that the growth of S. aureus on an agar was inhibited by a mold that had contaminated the plate
The mold Penicillin notatum produces a compound called penicillin
Penicillin was shown to possess antibacterial activity against streptococci, meningococci, and Corynebacterium diphtheriae
Adherence
Attachment/adherence is often the first step in bacterial pathogenesis
Adherence is a virulence trait, adhesins/pili/fimbriae are the virulence factors
Bacterial pathogens express adhesins of their surface that binds to a receptor on the surface of a host cell
Pili/fimbriae mediate long-range attachment
Other adhesins mediate short-range attachment
Ehrlich’s Magic Bullet
In the early 1900s, the German physician and scientist Paul Ehrlich set out to identify a “magic bullet” to treat infections by targeting infectious microbes without harming the patient.
After screening over 600 arsenic-containing compounds, he found one that targeted the bacterium Treponema pallidum, the causative agent of syphilis.
The compound was found to successfully cure syphilis in rabbits and soon after was marketed under the name Salvarsan as a remedy for the disease in humans
Ehrlich’s approach of systematically screening a wide variety of compounds remains a common strategy for the discovery of new antimicrobial agents today
autoinducer
Quorum sensing signal, binds to receptor protein(s)
Constitutively expressed
If many bacteria are nearby, a lot of quorum sensing signal will be present in the local environment
If enough quorum sensing signal enters into the cell, expression of certain genes will be induced leading to group behaviors (e.g. biofilms)
Can occur between alike and different bacteria
therapeutic index (TI)
Measure of the safety of an antimicrobial drug
Calculated as the ratio of Tolerable Dose: Effective Dose
Tolerable dose: how much host can tolerate without getting harmed
Effective dose: dose required to kill bacteria
We want tolerable dose to be high and effective dose to be low
Higher TI = safer the drug (read: a wide range of doses are tolerable yet effective)
Minimal Inhibitory Concentration (MIC)
The smallest concentration necessary to kill/inhibit bacteria
Determines effectiveness of an antibiotic
Antibiotic is serially diluted in broth, then bacteria is added to each tube and incubated
MIC corresponds to the tube with the lowest concentration of antibiotic without growth
Why do pathogens cause disease?
They are trying to survive and reproduce
Humans just happen to be harmed in the process
Many pathogens cause symptoms that aid in their transmission
How many pathogens are required for infection?
Depends on the pathogen (and portal of entry)
ID50
The number of cells required to produce an infection in 50% of a population
ID = infectious dose
LD50
The number of cells required to cause death in 50% of a population
LD = lethal dose
Often done in animals not humans for ethical reasons → results in less precise data for human infections
Siderophores
Secreted by some pathogenic bacteria
‘Steal’ the iron from the host’s iron-transport proteins
Bacterial cells express a siderophore receptor on their surface to mediate uptake of the siderophore-iron complex; binds to siderophore to bring it back
Siderophore binds to iron inside the body, bacteria import siderophore back into itself to use the iron
Antigens
Bacterial pathogens change the identity of the proteins expressed on their surface (antigens) that could be recognized by our immune system
Allow the bacteria to outrun the immune response (takes ~1 week to produce antibodies)
The new ones made evade detection by the antibodies produced; gives 1 week head start
Immune responses (antibodies) are specific to the proteins of the bacteria (antigens)
Host recognizes infection occurring → immune system produces antibodies that match the antigens present (takes ~1 week) → means pathogen can increase in number → antibodies produced + bind to antigen + kill antigen → number of bacterial cells drops
Prions convert what to what
Convert a normal host protein (PrPC) into a misfolded version (PrPSc)
The human genome encodes and human cells normally express PrPC
The secondary structure of the normal PrPC protein is primarily alpha helices
When PrPC encounters a prion, its secondary structure changes to beta sheets and is then referred to as PrPSc
Properly folded → misfolded (PrPSc)
The PrPSc then converts more PrPC to PrPSc leading to the formation of amyloids that interfere with cellular functions
Antimicrobial drugs must exhibit ______ _________ to have clinical relevance
selective toxicity; targets components/process that are present in the microbe but absent in the host
Ex. bacteria have cell walls composed of peptidoglycan, humans do not
Selective toxicity is relatively easy to achieve for antibiotics because there are many cellular differences between prokaryotes and eukaryotes
E.g. ribosome structure
Selective toxicity is much harder to achieve for viruses (use host machinery to replicate) and fungi (eukaryotes like humans)
Many antivirals and antifungals harm the human host
Selective toxicity
affect the microbe without harming the host
Baltimore classification system
Differs between viruses with:
A DNA vs RNA genome
A double-stranded (ds) vs single-stranded (ss) genome
A positive (+) sense vs negative (-) sense genome
+ : genes are on that strand
- : genes on other strand
dysbiosis
Altering of the microbiota
Can lead to infection
Caused by a number of factors including use of antibiotics
