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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