Viruses and Bacteria

1
Viruses and Bacteria

• Chapters 18, 19 and 27

2
T4 bacteriophage infecting an E. coli cell
3
Bacteria Viruses

• Of interest to us mostly because of the diseases
  they cause (harmful pathogenic)
• Bacteria cause about half of all human diseases
• Typically cause disease by exotoxins or
  endotoxins
• Exotoxins are secreted and cause disease even if
  the bacteria that produce them are not present
• Endotoxins are released only when bacteria die
  and their cell walls break down

4
Figure 27.20

• In Lyme disease, proteins instead of toxins are
  released that compromise the host immune system.
  It is caused by a bacterium and carried by ticks

5 ?m
5
Virus, bacterium, animal cell
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Viruses (Chapter 19)

• Basically a genome enclosed in a protective
  protein coat
• Are not considered to be alive
• The tiniest viruses are only 20 nm in
  diametersmaller than a ribosome.

7
Viruses

• Depending on the type of virus, their genome
  consists of
• double-stranded or single-stranded DNA or
  double-stranded or single-stranded RNA
• Capsid protein shell enclosing the viral genome.
• Some also have structures to help them infect
  their hosts
• For example, a membrane envelope (derived from
  the cell membrane of the host cell) surrounds the
  capsids of flu viruses.

8
Viral structure
9
Viruses

• Can reproduce only within a host cell.
• Each type can infect a limited range of host
  cells.
• The fit is between proteins on the virus
  surface and specific receptor molecules on the
  hosts surface.
• Some can infect several species, while others
  infect only a single species.
• Examples
• West Nile virus can infect mosquitoes, birds,
  horses, and humans.
• Measles virus can infect only humans.
• Most viruses of eukaryotes attack specific
  tissues.
• Human cold viruses infect only the cells lining
  the upper respiratory tract.
• The AIDS virus binds only to certain white blood
  cells.

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Viruses

• A viral infection begins when the genome of the
  virus enters the host cell.
• Once inside, the viral genome takes over its
  host, causing the cell to copy viral nucleic acid
  and manufacture viral proteins.
• The host provides the materials (nucleotides,
  amino acids, ATP, etc.) for making the viral
  components dictated by viral genes.

11
Viruses

• Reproduce using lytic or lysogenic cycles.
• Lytic cycle Results in the death of the host.
• In the last stage of the cycle, the infected cell
  lyses (breaks open) and releases the viruses
  produced within the cell.
• Each virus can spread to infect another healthy
  cell.

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The lytic cycle of phage T4, a virulent phage
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Viruses

• Lysogenic cycle The viral genome replicates,
  doesnt destroy the host cell.
• Lambda phage that infects E. coli does both types
  of cycles.
• Infection of an E. coli by lambda begins as
  usual .
• What happens next depends on the reproductive
  mode
• During a lysogenic cycle, the viral DNA molecule
  is incorporated into the host cells genome.
• When the host divides, it copies the phage DNA
  and passes the copies to daughter cells.
• Viruses propagate without killing the host cells.
• Viruses may enter the lytic cycle at a later time
  .

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Lytic and lysogenic cycles of ? phage
15
Bacteria Defenses

• Phages can wipe out an entire bacterial colony
• Natural selection favors bacterial mutants with
  receptor sites that are not recognized by phages.
• Bacteria produce restriction endonucleases, or
  restriction enzymes, that recognize and cut up
  foreign DNA, including phage DNA.
• Natural selection favors phage mutants that are
  resistant to restriction enzymes.

16
Envelope Viruses

• Viruses with an outer envelope use it to enter
  the host cell.
• The envelope fuses with the host membrane, moving
  the capsid and viral genome inside.
• After the virus assembles, it buds from the host
  cell.
• The viral envelope is thus derived from the
  hosts plasma membrane.
• These enveloped viruses do not necessarily kill
  the host cell.
• Example
• The herpes virus is an envelope virus (nuclear
  envelope of host).
• In some cases, copies of the DNA from herpes
  virus (which causes chicken pox, for example)
  remains behind as mini chromosomes in the nuclei
  of certain nerve cells.
• There they remain for life until triggered by
  physical or emotional stress to leave the genome
  and initiate active viral production (e.g.,
  shingles).

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RNA Viruses

• RNA is the genetic material
• Retroviruses have the most complicated life
  cycles.
• These have an enzyme called reverse transcriptase
  that transcribes DNA from an RNA template (RNA ?
  DNA).

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Viruses

• Human immunodeficiency virus (HIV), the virus
  that causes AIDS (acquired immunodeficiency
  syndrome) is a retrovirus.
• HIV attacks the cells of the immune system
• HIV can weaken the immune system so it is
  difficult to fight off certain opportunistic
  infections.
• These are usually controlled by a healthy immune
  system
• They can be life-threatening in someone with
  AIDS.

19
Viruses Disease

• Some viruses damage or kill cells by triggering
  the release of hydrolytic enzymes from lysosomes.
• Some cause the infected cell to produce toxins
  that lead to disease symptoms.
• Others have molecular components, such as
  envelope proteins, that are toxic.
• In some cases, viral damage is easily repaired
  (e.g., damage to respiratory epithelium after a
  cold), but in others, infection causes permanent
  damage (e.g., damage to nerve cells after polio).
• Many temporary symptoms associated with a viral
  infection result from the bodys own efforts at
  defending itself against infection.

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Classes of Animal Viruses
21
Viruses

• The immune system is a complex part of the bodys
  natural defense against viral and other
  infections.
• Vaccines are harmless forms or parts of pathogens
  that stimulate the immune system to mount
  defenses against the actual pathogen.
• Vaccination has eradicated smallpox.
• Effective vaccines are available against polio,
  measles, rubella, mumps, hepatitis B, HPV, and a
  number of other viral diseases.
• Some viruses do not yet have effective vaccines.

22
Viruses

• The influenza pandemic of 1918-1919 killed more
  people than World War I, at somewhere between 20
  and 40 million people.
• It was the most devastating epidemic in recorded
  world history.
• More total people and proportionately more people
  died of influenza in this single year than in the
  four years of the Black Death/Bubonic Plague from
  1347 to 1351.

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Viruses

• Medicine can do little to cure viral diseases.
• Antibiotics are powerless against viruses.
• Most antiviral drugs interfere with viral nucleic
  acid synthesis.
• An example is acyclovir, which impedes herpes
  virus reproduction by inhibiting the viral
  polymerase that synthesizes viral DNA.
• Azidothymidine (AZT) curbs HIV reproduction by
  interfering with DNA synthesis by reverse
  transcriptase.
• Currently, multi-drug cocktails are the most
  effective treatment for HIV.

24
Viruses

• New viral diseases are emerging.
• HIV, the AIDS virus, seemed to appear suddenly in
  the early 1980s. The actual first case was likely
  at least as far back as the 1950s, but it did
  not become an epidemic at that time.
• Each year new strains of influenza virus cause
  millions to miss work or class, and deaths are
  not uncommon.
• The deadly Ebola virus has caused hemorrhagic
  fevers in central Africa periodically since 1976.
• West Nile virus appeared for the first time in
  North America in 1999.
• A recent viral disease is severe acute
  respiratory syndrome (SARS).

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New Viral Diseases

• The emergence of new viral diseases is due to
  three processes
• I. Mutation of existing viruses
• Some mutations create new viral strains different
  enough from earlier strains that they can infect
  individuals who had acquired immunity to these
  earlier strains (e.g., flu).

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New Viral Diseases

• II. The spread of existing viruses from one host
  species to another.
• It is estimated that about ¾ of new human
  diseases originated in other animals.
• For example, hantavirus, which killed dozens of
  people in 1993, normally infects rodents,
  especially deer mice.
• The source of the SARS-causing virus is still
  undetermined, but candidates include the exotic
  animal markets in China.

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New Viral Diseases

• III. The spread of existing viruses from a small,
  isolated population to a widespread epidemic.
• AIDS went unnamed and virtually unnoticed for
  decades before spreading around the world.
• Affordable international travel, blood
  transfusion technology, sexual promiscuity, and
  IV drug abuse, allowed a previously rare HIV to
  become a global problem.
• Changes in host behavior and environmental
  changes can increase the viral traffic
  responsible for emerging disease.
• Destruction of forests to expand cropland may
  bring humans into contact with other animals that
  may host viruses that can infect humans.

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Prions

• Prions are infectious proteins that spread
  disease.
• They appear to cause several fatal degenerative
  brain diseases.
• Examples mad cow disease, and
  Creutzfeldt-Jakob disease in humans, a
  transmissible spongiform encephalopathy that
  results in the destruction of brain cells. It can
  be inherited or contracted by consuming material
  from animals infected with the bovine form.
• Prions are likely transmitted in food and have
  two alarming characteristics.
• 1. Slow-acting, with an incubation period of
  around ten years.
• 2. Virtually indestructible, not destroyed or
  deactivated by heating to normal cooking
  temperatures.

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how prions propagate

• According to the leading hypothesis, a prion is
  an improperly folded form of a normal brain
  protein.
• When the prion gets into a cell with the normal
  form of the protein, the prion can convert the
  normal protein into the prion version, causing a
  chain reaction that leads to more prions.

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Bacteria (Chapter 27)

• The major component of the bacterial genome is
  one double-stranded, circular DNA molecule that
  is associated with a small amount of protein,
  tightly coiled in the nucleoid (no membrane).
• E. coli has about 4.6 million base pairs with
  about 4,400 genes.
• This is 100 times more DNA than in a virus and
  1,000 times less than in a eukaryote.

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Plasmids

• Many bacteria also have plasmids, much smaller
  circles of DNA.
• Each plasmid has only a small number of genes,
  from just a few to several dozen.
• In the 1950s, Japanese physicians began to notice
  that some bacterial strains had evolved
  antibiotic resistance.
• The genes for resistance are carried by plasmids,
  specifically the R plasmid (R resistance). Some
  of these genes code for enzymes that destroy
  antibiotics (e.g., ampicillin).
• Through natural selection, the fraction of
  bacteria with genes for resistance increases in a
  population exposed to antibiotics
• Antibiotic-resistant strains of bacteria are
  becoming more common

32
Bacteria

• Divide by binary fission (after DNA replication)
• Proliferate very rapidly.
• Under optimal laboratory conditions, E. coli can
  divide every 20 minutes, producing 107 to 108
  bacteria in as little as 12 hours.
• In the human colon, E. coli grows more slowly and
  can double every 12 hours, reproducing rapidly
  enough to replace the 2 1010 bacteria lost each
  day in feces.

33
Bacteria

• Most bacteria in a colony are genetically
  identical to the parent cell, but there are
  mutations as well.
• The spontaneous mutation rate of E. coli is 1
  10-7 mutations per gene per cell division.
• This produces about 2,000 bacteria per day in the
  human colon that have a mutation in any one gene.
• About 9 million mutant E. coli are produced in
  the human gut each day.
• Individual bacteria that are genetically well
  equipped for the local environment clone
  themselves faster than do less fit individuals.

34
Bacteria

• Genetic recombination produces new bacterial
  strains.
• Recombination is the combining of DNA from two
  individuals into a single genome.
• Bacterial recombination occurs through three
  processes transformation, transduction, and
  conjugation.

35
Bacteria

• I. Transformation Uptake of foreign DNA from the
  environment.
• Many bacteria have surface proteins specialized
  for the uptake of DNA.
• E. coli can be induced to take up DNA if grown in
  a relatively high Ca2.
• Plasmids are often used in transformation
  experiments to move new DNA with new traits into
  bacteria.

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Bacteria

• II. Transduction a phage carries bacterial genes
  from one host cell to another.
• III. Conjugation bacterial cells are temporarily
  joined and transfer genetic material.

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Bacteria Gene Expression

• Chapter 18.1

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Bacteria Gene Expression

• Individual bacteria can respond to environmental
  change by regulating their gene expression.
• Cells can vary the number of specific enzyme
  molecules they make.
• Cells can also adjust the activity of enzymes
  already present (e.g., by feedback inhibition).
• There are two types of enzyme controls
  repressible and inducible

39
Bacteria Gene Expression

• Repressible enzymes function in anabolic pathways
  (building up).
• They are usually functioning (i.e., ON), and
  are turned off when not needed
• When there is enough end product present, the
  cell can stop production (i.e., turn OFF).
• Inducible enzymes function in catabolic pathways
  (breaking down).
• They are usually not functioning (i.e., usually
  OFF)
• When a substance needs to be digested, the cell
  starts production (only turned ON when needed).
• Both are examples of negative control.

40
Tryptophan

• Controlled through repressible enzyme pathway
• Forms in a series of steps, with each reaction
  catalyzed by a specific enzyme.
• The five genes coding for these enzymes are
  clustered together, served by a single promoter,
  and are all made together at one time.
• One long mRNA codes for all five enzymes.
• A single on-off switch controls these related
  genes.
• Similar to coordinately controlled genes in
  eukaryotes.

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Tryptophan

• The switch is a segment of DNA called an
  operator.
• The operator, located between the promoter and
  the genes, controls the access of RNA polymerase.
• The operator, the promoter, and the genes they
  control constitute an operon.
• The basic mechanism for this control of gene
  expression in bacteria, the operon model, was
  discovered in 1961 by François Jacob and Jacques
  Monod.

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Trp Operon Usually ON
43
Trp Operon

• Normally, the trp operon is on
• However, if a repressor protein, a product of a
  regulatory gene, binds to the operator, it can
  shut the system off.
• Each repressor fits only to the operator of a
  certain operon.
• Repressors are always present at low rates.
• When tryptophan concentrations are high, some
  tryptophan molecules bind as a corepressor to the
  repressor protein.
• This activates the repressor and turns the operon
  off.

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Trp Operon OFF
45
Lactose

• Lactose regulation displays inducible control
  (usually off).
• The lac operon contains a series of genes that
  code for enzymes that break down and metabolize
  lactose.
• In the absence of lactose, this operon is off, as
  an active repressor binds to the operator and
  prevents transcription.
• The enzymes are only needed when lactose is
  present and needs to be broken down.

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Lac Operon Usually Off
47
Lactose Regulation

• Lactose breakdown begins with lactose hydrolysis.
• Catalyzed by the enzyme ß-galactosidase.
• Only a few molecules of this enzyme are present
  in a cell grown in the absence of lactose.
• Adding lactose increases the number of
  ß-galactosidase enzymes 1000x within 15 minutes.
• The gene for ß-galactosidase is part of the lac
  operon, which includes two other genes coding for
  enzymes that function in lactose metabolism.

48
Lactose Regulation

• The regulatory gene codes for a repressor protein
  that can switch off the lac operon by binding to
  the operator.
• Unlike the trp operon, the lac repressor is
  active all by itself, binding to the operator and
  switching the lac operon off.
• An inducer inactivates the repressor.
• When lactose is present in the cell, allolactose,
  an isomer of lactose, binds to the repressor.
• This inactivates the repressor, and the genes of
  the lac operon can be transcribed.

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Lac Operon On
50
The Lac Operon

• The lac operon is also affected by positive
  control
• Glucose is a preferred food source of E. coli
• If glucose is present, the operon is off,
  regardless of lactose levels
• If only lactose is present, lac operon activity
  is accelerated by catabolite activator protein
  (CAP) binding to cAMP and then to a site upstream
  of the promoter