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 10 3 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 T helper 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.Entry 2.Insertion of genetic material 3.Replication of genetic material 4.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