Bacterial Toxins and Viruses

Bacterial Toxins

• Review of last week's content on exotoxins (6 slides).
• New content on bacterial toxins.
• Short break, then viruses.
• Longer break at 12:00.

Bacterial Pathogenesis

• Bacteria cause disease through pathogenesis.
• Toxins are released, causing disease.
• Two types of toxins:
  • Exotoxins: secreted by bacteria.
  • Endotoxins: released when gram-negative bacteria die and cell walls break up, releasing lipopolysaccharides.

Exotoxins

• Produced by some bacteria.
• Usually proteins.
• Heat-labile (destroyed by heating).
• Secreted or released as bacteria exist.
• Specific effects on host cells.
• Often very toxic (e.g., botulism).
• Elicit an antibody response.
• Many can be made into vaccines.
• Some bacteria produce a single toxin, others produce many.
• Botulism: most poisonous substance known.
• Classified as:
  • Neurotoxins: affect the nervous system.
  • Enterotoxins: affect the gut.
  • Toxemia: widespread effect via the blood.

Table of Exotoxins

• Lists exotoxins, bacteria that produce them, and their effects.

• Some toxins insert a doughnut-shaped protein, creating a permanent hole in cells, causing fluid leakage and cell bursting.

  • Example: Streptococcus pyogenes causes red blood cells to burst (hemolysis).

• Beta-hemolytic strep example on an agar plate, showing blood cell bursting.

Diphtheria

• Affects abnormal tissue growth across the throat, causing respiratory obstruction.
• Was an epidemic in the 1850s-1860s.

Cholera

• Still affects humans today.
• Cholera toxin secreted from Vibrio cholerae (curved bacteria).
• Toxin binds to cells lining the intestine, changing cell function.
• Increases production of cyclic AMP.
• Uncontrolled secretion of chloride, followed by water.
• Loss of 10-20 liters of water into the gut, leading to extreme dehydration and possible death within a day.

Neurotoxins

• Produced by Clostridium tetani and Clostridium botulinum.
• Two of the most potent toxins known.

Tetanus

• Clostridium tetani grows in deep necrotic puncture wounds (dead tissue).
• Bacteria are anaerobic (find oxygen toxic).
• Produces uncontrolled rigid muscle contraction.
• Early symptoms: locked jaw.
• Severe muscle spasms can crush spinal bones.
• Toxin blocks inhibitory neurotransmitters that tell muscles to stop contracting.
• Causes titanic spasm (severe cramp). Significant effect; painting from 1809 shows someone in tetanus during the Napoleonic Wars.

Cerebral Palsy & Botulinum Toxin (Botox)

• Brain is damaged in utero or at birth, leading to loss of voluntary muscle movement.
• Children typically born with flaccid muscles that become tense over time (spasticity).
• Muscles fix in a position, causing problems with care and risk of fungal infections.

Botox

• Derived from botulinum toxin, creates flaccid paralysis.
• Relaxes tense muscles in cerebral palsy, lasting about six months.
• Blocks the release of neurotransmitters (acetylcholine) that stimulate muscle contraction, resulting in muscle paralysis.

Botulinum Toxin

• Produced by Clostridium botulinum, causes paralysis.
• Found in improperly sterilized canned foods.
• Toxin is ingested directly from contaminated food.

Super Antigens

• Stimulate the immune system in a very big way, activating large numbers of cells.
• Cause fever, low blood pressure, and fluid loss.
• Lead to septic shock.
• Overwhelm the immune system.
• Staphylococcus aureus causes toxic shock syndrome.
• Streptococcus pyogenes also does that.
  • T cells stimulate cell-mediated immunity.
  • Cytokines are signaling molecules between cells.
• Result in toxic shock: temperature increases, blood pressure decreases, rash appears, skin on palms and soles may peel.

Antitoxins

• Treat toxins by neutralizing them.
• Antidotes derived from serum of humans or animals (e.g., horses) exposed to the toxin.
• Animals develop antibodies (immunoglobulins).
• Antibodies are harvested and used to neutralize the toxin.
• Essential for treating tetanus and botulism, where mortality is high without treatment.
• Provide immediate antibodies faster than the body's own response.

Endotoxins

• Lipopolysaccharides on gram-negative bacteria.
• Effects exerted when the cell wall breaks down.
• Lipopolysaccharides released during infection.
• Increasing bacterial death releases more endotoxin.
• Antibiotics may initially worsen symptoms by killing bacteria and releasing more endotoxin.
• Symptoms: fever, muscle weakness, aches and pains, diarrhea, feeling unwell. Can result in septic shock.
• Older people or those with poor immune systems are more susceptible.
• Mechanism of death: blood capillaries leak fluid, leading to physiological shock.

Exotoxins vs. Endotoxins

Bacterial Immune Evasion

• Bacteria evade the body's attack after entry.
• Phagocytes: cells that engulf bacteria.
• Some bacteria block or avoid phagocytosis.
• Chemotaxis: attraction of leukocytes (white cells) to the area of infection.
• Some bacteria block chemotaxis.
• Capsules prevent phagocytosis.
• Concealment: hiding inside cells or in areas with few defense cells (e.g., brain).

Summary of Bacterial Pathogenesis

• Disease is a loss of balance between disease and health.
• Infections: endogenous (from elsewhere on the body) or exogenous (from the environment).
• Disease depends on:
  • Virulence: ability to cause disease.
  • Infective dose: number of bacteria.
  • Adherence: ability to stick to the host, aided by pili, slime layers, and biofilms.
  • Toxins: damage and cause disease.

Summary of Toxins

• Exotoxins: damage cells by breaking them open, interfering with their function, or interfering with nerve function, may by super antigens.
• Treatment: vaccination (toxoids) or antitoxins.
• Endotoxins: lipopolysaccharides in cell walls cause fever and septic shock.
• Brief Pause (Three to four minutes)
• Lecture Shifts into Viruses.

Viruses

Introduction to Viruses

• Viruses are responsible for many significant diseases.
• New viral diseases are continually emerging(e.g., COVID-19, AIDS, SARS).
• Most new diseases in humans over the last 60 years have been caused by viruses.

Origin of the Word "Virus"

• Comes from a word meaning "venom" or "poison."
• Originally referred to as "filterable viruses" because they could pass through filters that trapped bacteria.

Viral Impact on Life

• Viruses affect all life forms, including bacteria.

SARS (Severe Acute Respiratory Syndrome)

• SARS, MERS, and COVID-19 are respiratory diseases caused by coronaviruses.
• COVID-19 spreads faster and may cause more severe illness.

SARS-CoV-2 compared to Previous Coronavirus Outbreaks

• SARS-CoV-2 seems to spread faster and cause more severe illness than SARS-CoV.

Characteristics of Viruses

• Smallest infectious agents (except for prions and plasmids).
• 10-100 times smaller than bacteria, 500 times smaller than red blood cells.
• Require electron microscope to view.
• Lack enzymes for metabolism and synthesis.
• Replicate by invading host cells and using host machinery.
• Classified as obligate intracellular parasites.
• Cause damage by causing cells to break open, lose function, or die.

Virus Structure

• Simpler structure than cells.
• Contain nucleic acid (DNA or RNA).
• Have a protein coating called a capsid.
• May have an additional envelope.
• Not considered living organisms.
• Classified based on shape and structure.

DNA

• Two long, twisted strands with complementary genetic information.
• Gene: segment of DNA that confers a particular trait.
• Chromosome: entire package of DNA contained in the nucleus of a cell (not in viruses).

Viral Nucleic Acid

• Only one type of nucleic acid (single or double-stranded RNA or DNA).
• Viral genome does not carry all information necessary for synthesis and reproduction.
• Initiates process in the host cell to make proteins.
• Directs the host cell to make new viral particles.
• Genome: complete set of genes.

Viral Capsid

• Protein coat covering the nucleic acid.
• Arranged in symmetrical patterns, giving distinctive shapes.

Viral Shapes

• Variety of shapes depending on capsid arrangement and presence of an envelope.
• Examples:
  • RNA viruses: parvovirus, T2 bacteriophage.
  • DNA viruses: herpes virus, tobacco mosaic virus.
• Bacteriophages:
  • Invade bacteria; T2 bacteriophage attaches to bacteria, injects nuclear material.

Electron Microscopic Images

• Electron microscope needed to see viruses.
• Image of virus causing gastroenteritis in children; immunization now available.
• Various virus shapes illustrated.
• Bacteriophages coloured versions shown.

Virus Structure Details

Enveloped Virus

• Example: cytomegalovirus (CMV).
• Contains nuclear material (double-stranded DNA).
• Protein coat (capsid).
• Envelope: a lipid bilayer with glycoproteins (spikes).
  • Glycoproteins (spikes) used to stick to cells and determine how our body recognizes the virus (antigenic characteristic).

Viral Envelope

• Outer layer present on some viruses.
• Double layer of lipids (fats).
• Obtained from host cell.

Spikes

• Glycoprotein spikes protrude from the envelope.
• Used by virus to stick to host cells.
• Determine antigenic characteristics (how the body recognizes the virus).

Naked Viruses

• Viruses without an envelope.
• More resistant to environmental changes (e.g., dryness, heat).
• Chemicals, extremes of pH, or temperature can affect viral function.

Diagrammatic Representation of Virus Components

• Glycoprotein spikes
• Lipid membrane
• Capsid
• Enzymes
• RNA(single strand nucleic acide)
• Reverse transcriptase

Viral Replication Video

• Virus binds to cell surface via matching “keys” on the virus and “locks” on the cell.
• Cell membrane folds inward, engulfing the virus.
• Virus capsule bursts, releasing “secret recipe” (viral code) into the cell nucleus.
• Cell nucleus makes copies of virus recipes.
• New virus components are assembled.
• Cell erupts, releasing millions of new viruses.
• The host immune system usually works to keep viruses in check.

Cell Surface Receptors

• Cell membrane is a barrier.
• Receptors: doors in the cell membrane that transmit instructions.
• Receptors are vital to life but become a vulnerability with viruses.
• Receptors connect with molecules outside the cell.
• Viruses mimic natural molecules, causing them to connect to cell receptors.

Enzyme in Viruses

• Most enzymes involve reverse transcriptase and neuraminidase in making copies of nuclear material.
• These enzymes can be targets for antiviral drugs.

How Viruses are classified

• Classified based on:
  • DNA type (double-stranded or single-stranded DNA, double or single-stranded RNA).
  • Shape (cylindrical enveloped or naked).
  • Replication inside human cell

Host and Cell Specificity

• Plants, bacterial and animal viruses only affect those hosts.
• Depends on receptors on the surface for infection.
• Coronavirus causes coronavirus, corvids affect birds and mammals
• COVID 19 affect humans well.

Host Receptors and COVID-19 Context

• Ability to move across a single species
• Bats > Humans
• Previous CoV: In Palm civets, in dromedary camels
• Bats- COVID most likely, same with SARS.

COVID-19

• Coronavirus Disease 2019.
• SARS CoV 2 (similar to Bats). The virus, its name is severe acute respiratory syndrome coronavirus two or SARS COVID Cov two.
• SARS CoV – China. Began there, affected 24
• Middle Eastern. Saudi Arabi. Affected Two and Half Thousand and 800 deaths, fatality 35
• The Covid 19 has a virus with no shape. Ranges from Nano meters.
• Can be changed by UV Light/Heat 27 degrees to stop replication.
• 89-82% the same, evolved from a strain of Bats.

The Receptors

• Various shapes. Spheres must match with cell.
• Surface Markers on viruses that match with cells.

Virus Specificity

• Same receptors on cell makes vulnerable to different viruses. But many viruses may have same types of surface.
• Various shapes, and cells may have all sort of shapes.
• Virus A has the shape Virus B has a triangle
• Polio virus: binds specific receptors on primate cells (monkeys humans).

Conditions for Successful infection

Virus Storages

• Obligate parasit, cell must die so takes months to die inside a cell.

• Can a virus change shape. 2 viruses may become to viruses, if infected the swap genetic info.
  *
  Animal Reservoirs

• Rabies- Rodent, dogs, bats. Long periods of time, in animals

• Other don’t such a dog dies.

• Hantavirus In mouse deer. Causes Influenza

• Fruit bats, from fecal of fruit bat. Henry is an example. Spreads to horse than humans.

• Virus die or animal lives and flyies but cause infection to animal when bites you

• Store in animal cell, due the virus lives for long animals live around it. Just animal store water that store.

• If Virus has many surface receptor it is easier to Infect

• Influenza to chickens/Ducks that will go to Humans
  Commensalism does have that

• Mosquitoe has Arbovirus. Gives dengue

• Have insect, Live and give the virus to you.

Viral Reproduction(Replication)

• Virus need to adhere and stick here.

Step 1

Adsorption- Shape matches, attches host cell human to viral capsid of that enevople.

Step 2

Penetrates- gets inside the cell via 3methods:

• Directly
• Membranse fusion
• By swallowing.

Step 3

• Takes 3 mintues to break by into parts into nuclear into that stuff, that replication that takes about that
  • Virus needs nuclear to replication. This way cov works that virus that way.

Two mechnamism By which enveloped viruses enter Humans

• Viron attches for protiens surface called spikes; virus the with
• Nucolo caipdi releasd to toplams, niclei acids septates for the protien coat
• Adsorps to host cell
• Virision its and of for vesicle
• Virus does release acids released throught the virus
• Since no ever lope, cannot with membrance.
• Getting it is process this is not getting good

How body responds to Infcetion

• Some have no effects asmypatic, but to change or sytomosm
• Somes cell die can sign of syndrome
• So to chan to warts by changing. So warts and can chaned can causde cand
• Viruses may be trasmited or by treated . But viruses always get a prevented
  The Process gives way preventions

Common Viral Diseases

• Refer to table listing diseases their viruses and families.
• 3 – 4 virisions is what we think. Causes jaundice.