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Infection
When invaders get past our
defenses
Phylogeny of Eukarya
Which lineages are major
causes of disease
• Bacteria
– Tuberculosis (Mycobacterium sp.)
• Eukaryotic protozoans
– Malaria (Plasmodium sp.)
• Viruses
– Contemporary: HIV, Dengue, Influenza
– Historic: Smallpox, measles, polio, influenza
Bacterial lineages
Many are
pathogenic
* Some are only
pathogenic when they
escape from their
normal environment
How do antibacterials prevent
growth?
•
Interfere with or halt:
1. bacterial cell-wall synthesis
•
Peptidoglycan layer
2. bacterial protein synthesis
•
Interrupt various phases of protein formation
3. Bacterial DNA replication & repair
Morphology &
Antibiotics
• Antibacterials target
synthesis of
peptidoglycan
• Gram stains = proxy
for type of cell wall
– Gram + = lots of
peptidoglycan; no outer
membrane
– Gram - = little
peptidoglycan; outer
membrane present
Why does that result in clearing a
bacterial infection?
• Your immune system does most of the
work:
– kills or devours bacteria & infected cells
Why does that result in clearing a
bacterial infection?
• Your immune system does most of the
work:
– kills or devours bacteria & infected cells
• Antibacterials simply help out:
– Suppress growth rate of bacteria
– Reduce absolute number to a manageable
amount
• Show antibiotic susceptibility
2 Evolutionary forces
• Natural Selection: survival of “whatever
works”
– Human immune system
– Antibacterial drugs
• Mutation - Errors in copying genetic code
– Introduces variation; some of this variation
increases probability of reproducing
Commonalities & Consequences
• Common to ALL:
– Haploid - All mutations are “visible to selection”
– Reproduce by fission (1 -> 2 daughter cells;
vertical gene transfer)
• Like mitosis in that daughter cell is an exact copy of
parent cell
– Capable of conjugation (horizontal/lateral gene
transfer)
• Transfer extracellular plasmids (parasitic genomes)
& sometimes their own genes via conjugation tubes
– No genetic repair mechanisms - Errors in
copying (mutations) are not fixed.
Why does resistance evolve?
• Strong selection for resistance
– Drugs, immune system
• Large population sizes & rapid reproduction
– Many mutants per generation
• Rapid mutation rate
– No repair mechanism; small genome; little “junk” DNA
• Wildly promiscuous = new gene combinations
– Conjugation tubes for exchange of “resistance genes”
How does resistance evolve?
1.
Overproduce efflux pumps
–
Proteins that eject an antibacterial before it can
work
2. Destroy the antibiotic
–
Lactamase destroys 103 penicillin molecules per sec.
3. Reprogram or camouflage the target of the
antibacterial
–
•
Change structure of protein synthesis machinery,
preventing erythromycin from binding to it.
Show Sumanas: Rise of antibiotic resistance
Which lineages are major
causes of disease
• Bacteria
– Tuberculosis (Mycobacterium sp.)
• Eukaryotic protozoans
– Malaria (Plasmodium sp.)
• Viruses
– Contemporary: HIV, Dengue, Influenza
– Historic: Smallpox, measles, polio, influenza
Morphological variation
How do viruses infect cells?
• Bind to receptor proteins studding the
host cell’s plasma membrane.
– Cells use membrane proteins to give
instructions, deliver goods, etc.
– LDL, glucose receptors
• HIV infects macrophages, replicates, and
later infects Thelper cells.
• Movie
Adaptive immunity
• Antigens stimulate adaptive immune response
– Self & foreign-antigens
• MHC molecules display antigens
• Types of Adaptive Immunity
– Antibody-mediated
• B cells; make antibodies to attack/immobilize invaders
– Cell-mediated
• T cells; contact kill infected cells
How to fight viruses?
•
Focus on 2 avenues
1. Vaccines - transferring immunity to a naïve
immune system
2. Antivirals - prevent efficient replication in
host
1.
2.
3.
4.
Entry
Insertion of genetic material
Replication of genetic material
Processing and packaging of new virions
Important morphological
variation
• Nonenveloped
– Enclosed by a shell of
protein (capsid)
• Enveloped
– Enclosed by capsid
AND membrane-like
envelope
Why does resistance evolve?
• Strong selection for resistance
– Drugs, immune system
• Large population sizes & rapid
reproduction
– Many mutants per generation
• Rapid mutation rate
– No repair mechanism; small genome
2 cycles of Virus production
1. Lytic cycle
1. Enter cell (via binding to proteins on plasma
membranes)
2. Replicate & transcribe genome
– Using host cell’s enzymes or their own (replicase
or reverse transcriptase)
3. Produce & process proteins
– Using host cell machinery & viral enzyme protease
4. Assemble new virions
5. Exit via budding or bursting
2 cycles of Virus production
2. Lysogenic cycle
1. Enter cell
2. Insert viral genome into host cell’s genome
– Using viral enzyme integrase
3. Lies latent; host cell reproduces it for free!
– No new viral particles produced; no infection of
unrelated cells (only daughter cells have viral
genome)
4. Switch to lytic cycle when host cell is
damaged, starved, challenged, etc.
Exiting host
• Host cell may
die
• Or, produce
more virions
How are viruses transmitted?
•
Depends. Whatever makes it successful
–
–
Measure of success = existence &
reproduction
Whatever strain of virus is passed on is
successful
1. Traits that optimize replication rates
2. Traits that optimize transmission rates