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 avenues1. Vaccines - transferring immunity to a

naïve immune system2. Antivirals - prevent efficient replication

in host1. Entry2. Insertion of genetic material3. Replication of genetic material4. 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 cycle1. 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 virions5. Exit via budding or bursting

2 cycles of Virus production

2. Lysogenic cycle1. Enter cell2. 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 rates2. Traits that optimize transmission rates