Should be able to give a basic definition of what these words mean, but more importantly, be able to say why

understanding these terms is r elevant to understanding antibiotics. Understand how terms are related to one another relationship between terms **join the soc gen 5 study group on facebook! :] (if you add jessica lin ill add you into the group!) Chriss Office Hours: Tues 10 AM Please all contribute! :) Plasticity- how far we can mold/stretch/change something Determination-theory that all things are an effect of preceding events Vivisection-changing physical structure through surgery Modernity - Add definition*** bringing technology back into the lab, mass producing antibiotics Artifice - human skill as opposed to what is natural HG Wells - trained under Huxley; studied in biology; struggled against class restraints of Victorian England (is your class in life defined at birth?) Hubris - assuming the position of God/ excess pride; we have hubris when we think we can eradicate disease by the use of antibiotics Bacterium-bacteria, single-celled organism that can cause disease, prokaryotic (have cell wall, no membrane-bound organelles, circular, not linear chromosomes, plasmids, smaller, different-shaped ribosomes Antibiotic - a chemical substance (of any origin) that possesses antibiotic powers. interfere with the bacterias structure, or inhibit it from being pathogenic Germ Theory of Disease - a single pathogen causes a single disease; Pasteur and Koch led to rise of lab/experiemental Pathogen (ic)-causes disease (not necessarily bacteria-fungus, virus, etc.)

 Kochs postulates - proof that the thing you found is causing the illness 1. The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy organisms. 2. The microorganism must be isolated from a diseased organism and grown in pure culture. 3. The cultured microorganism should cause disease when introduced into a healthy organism. 4. The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent. but anomalies found-carriers of disease dont show symptoms, variable symptoms. immune system proves germ theory Pasteur - had studies on fermentation and found that humans carry germs. Sparked a hygiene movement b/c things can spoil. Need to preserve food. Proved that spontaneous generation doesnt exist. isolated different cultures Pasteurization - a process of heating a food to a specific temperature for a predefined length of time and then immediately cooling it after it is removed from the heat. This process slows spoilage caused by microbial growth in the food. Unlike sterilization, pasteurization is not intended to kill all micro-organisms in the food. Instead, it aims to reduce the number of viable pathogens so they are unlikely to cause disease shows the changing mentality after the germ theory of disease, putting into practice ***Bacterial antagonism (Fleming) - inhibition of one bacteria by another. ex. penicillium. seen through antibiotics (Lecture 3) ***Selection (as in selective media/environments that select for certain traits)-choosing favorable traits that help them survive. driven by selective pressure. different stressors in the environment make them select because they make survival more possible Miracle drug - Penicillin, 1940s, used for many infections. mentality relates to hubris, controls disease. often misused. contributed to the decline of prevention. 1930s focused on prevention. started search for other antibiotics Selective toxicity - a broad term, but in our context it means harming prokaryotic cells and not eukaryotic - Narrow spectrum drug: selectively toxic to one type of bacteria and doesnt kill all bacteria. Helps lower antibiotic resistance -magic bullet -can target peptidoglycan (protein that structures the wall)

 Sulfonamide-prevents the multiplication of some types of pathogenic bacteria. interfere with metabolism. found through dyes- we can target parts of the cells and not others. didnt treat certain infections that penicillin could. lots of people have allergies Gram-negative/gram-positive - How does this relate to concept of selective toxicity? Gram Neg have an additional layer in their cell wall. Harder to kill negative than positive. Need to use different antibiotics because the permeability of the neg and pos are different. You will expect a different pattern of resistance The cell wall of Gram-positive bacteria is high in peptidoglycan which is responsible for retaining the crystal violet dye. cross-linked (tighter bond) now gram-negative are more antibiotic resistant Penicillium- produces penicillin. the mold itself. produces unstable form. difficulties of mass-producing. Florey and Chain mass-produced Penicillin-protein. discovered during WWII. miracle drug. discovered in 1939. deaths from infection dropped from 12-15% to 3%. also cured syphilis Cell wall-o Penicillin-interferes with the building of peptidoglycan. Causes cell to lyse Ribosome-tetrocyline intereferes with this synthesis Enzyme (eg. -lactamase)-works with and against resistance. can change active site so antibiotic cant inhibit function. B-lactamase- works on b lactase in penicillin, breaks it down. subtype:penicillin-mase Protein synthesis-tetracycline interferes. goes through the ribosomes. DNA synthesis-rifampin interferes Vat fermentation Nutrient medium-used to use yeast, then used corn liquor (more nutrients). liquid medium important because it allowed bacteria to grow on top of a medium, not inside it used agar for petri dishes. Mass production- 1951- $67 million dollars worth of penicillin created Streptomyces (aurofaciens)-from soil bacteria. first to treat tuberculosis. now chiefly used with other drugs because of its side effects Aureomycin-different strain, targets different things. Dugar-first. growth promoter in the 1950s. banned in Denmark Nosocomial infection: hospital-acquired infection. ex: MRSA. Sweden-2% MRSA are resistant 60% in USA. product of socialist health system where theres lots of control, prevent outbreaks more quickly Community acquired infection-daycares, prisons, crowded, concentrated areas of people. creates a generesevoir. structural violence. Pharynx-lots of horizontal gene transfer here. super dangerous because they can pass resistance. oral sex is dangerous. efficient way to get resistance of antibiotics because of

hair-like structures that scavenge DNA at the back of our throats (Sex and Superbug article) Transformation. Gonorrhea-veneral disease. morbidity vs. mortality. big in 1960s- sex revolution. affects which bacteria are more dangerous. biosocial phenomenom Triclosan-promotes antibiotic resistance because of all the selective pressure. effects cell membrane of antibacteria MRSA-nosocomial- started in ICU circa 1961. beds really close- led to high infection Iraqibacter-originally a soil bacteria that was harmless. developed virulence and resistance traits. resistance from horizontal gene transfer. acinetobacter gram negative. example of how bacteria/bacterial resistance spreads. repeated exposure/globalization/international gene resevoir Microbiology-study of microorganisms Mutation-change in DNA sequence. so much resistance that it cant just be from mutations Horizontal gene transfer-transfer of genes within the same generation of bacteria. conjugation, transposons (ride on regular chromosomes and plasmids) plasmids- easier to adapt, bacteriophages (viruses that affect bacteria) transduction, transformation (picking pieces of DNA from the environment) Selection Compliance: submissiveness of patient to follow the doctors orders (prescription dosage, etc.). - DOTS? Directly Observed Therapy, Short-Course. Doctors watch patient take drugs to ensure that patient complies. However, we do not have the resources (enough nurses, time, etc.) to provide DOTS, so patients cannot equally receive access to that kind of care. This is an example of structural violence. DOTS- prevents non-compliance. generally 1st line drugs Ethnography-scientific description of peoples and cultures. MDR/XDR tuberculosis- multi-drug vs. extremely-drug resistant. MDR-resistant to ionizids. XDR-ionizids and rifampicin. Multiple drug resistance- resistance to multiple drugs Structural violence- harms of social structures by preventing basic needs. discrimination. WHO-World Health Organization. monitors/keeps track of illnesses. cant make laws. pushing for antibacterial resistance research in lots of countries. hard to convince because of lack of data Amplification- bacteria divide quickly, exponential growth, amplifies problem of resistance in bacteria. social amplification- lack of knowledge leads to misuse of antibiotics-> greater resistance. Amplified when prisoners went home. Spread so quickly because so many people lived so tightly. Gene resevoirs. Peptide - a small chain of proteins (amino acid chain) innate immunity- some peptides confer immunity. First-line/Second-line antibiotic:

1st line drugs - ideal drug to take; cheaper; readily available. Often more broad spectrum, but not always 2nd line drugs - can be more expensive; often is more toxic to human; often takes longer (longer course of drugs), sometimes even over a year. Often more narrow spectrum, but not always. Tends to have less resistance

Wide-spectrum/narrow spectrum-targets wider range of bacteria-> more resistance>because of selective pressure. Diagnosis time-broad spectrum use to heal ASAP. Wide spectrum-more profitable-more people use Virulence Plasmid Conjugation Transposon- jumping gene Transduction-bacteriophages injects DNA into bacteria Bacteriophage Transformation-picking up free DNA Efflux pump-trait that can be overcome by antibiotics. Bacterias fight. Protein in cell wall. Gene reservoir Prophylaxis- intervene with antibiotics before any were sick. Drives up resistance CAFO (Concentrated Animal Feeding Operation)-example of amplification. Farmers are contracted, must follow protocol, industrialization of agriculture Economy of Scale- increase of efficiency by scaling up (Costco). Putting all farmers in one clump Revenue/Cost/Net Profit MarginNet profit margin=net profit/revenue Net profit=revenue-cost USDA, FDA, CDC - government is fragmented. Agencies lack strong authority over practices of individuals and companies. (compare US and Sweden.. hard for us to regulate) cant regulate, only suggest NARMS - National antimicrobial resistance monitoring system. This is on the rise, that is on the rise. It is a group that monitors AB resistance and reports it to groups, suggesting that they should do this or do that. Vs the system in Europe, which actually mandatesthings. Non-therapeutic antibiotics/sub-therapeutic dose Growth promoter Innate immunity-inherited, white blood cells. Also born with antibodies from mother Audit study Supply-side/demand-side phenomena

 Prescribing/Dispensing - separation of presciption (doctor) vs. dispensing (pharmacist) in US, vs in China, where prescribing and dispensing are the same place. Separation of profit making from prescribing and dispensing medicine. Morbidity/mortality - morbidity is the onset of the disease? Sickness vs death. CDC 2 million suffer from morbidity from antibiotics Patent protection Congress/legislation- not making progress. PAMTA- not passed. Reason for PAMTA is to make more centralized. Banned use of cephalosporin in animals (because it is used with humans) Tragedy of the commons - people take advantage of public goods that are given to them. Without constraining themselves. Problems arise where they think they could take a little more advantage and putting themselves above the common good. Ex: doctors prescribing too much antibiotics adds up on a greater scale; companies search for broad-spectrum drugs because theyre economically viable, but the collective good that is being harmed is that the bacteria gene pool are developing resistance to more drugs. Drug research & development pipeline- very strict guidelines make it very difficult to develop new antibiotics and drugs. Not wanting to make drugs because they no longer have patent Investment-research-production (test on animals)-efficacy-test on humans-FDA approvalindustrialization Hygiene- importance introduced by Pasteur. Surveillance- regulation of sale/regulation of antibiotics. Done in Denmark. DANMAP. Easier in smaller countries.

Prison System - Jails are becoming more crowded; receiving less funding - Cohorting: putting all infected people together (TB colony) - Social structure/institutional arrangement committing violence against people in prison - Biosocial problem

Many traits are latent and it doesnt even matter, but environment may shift and latent genes may prove beneficial

Selective pressure

B Lactam - for example, in the case of penicillin

Pathogenic vs virulence vs resistance: how are they different? Virulence: Has to do with how difficult it is to cure, but it really is about HOW SICK IT MAKES YOU. Particularly potent or toxic. Ex: swine flu (virulent strain of the flu). Its like a spectrum. Even if it affects two people different, if it is the same virus, theyre equally virulent?

Resistance: how hard it is to kill. DISTINCT FROM VIRULENCE. Gene reservoirs are resistant but not pathogenic. *Resistance has nothing to do with pathogenic*. Resistance and virulence are orthogonal things - like two separate axis - not related.

Pathogenic: anything that causes disease. Antibiotics are pathogens to bacteria. More black and white

Staphyloccus vs MRSA -

Timeline of Antibiotics - Discovery of Penicillin - First case of penicillin resistance - First use of growth promoters in food - Antibiotics put into mass production

- know basic mchisms for horizontal gene transfer - know how antibiotics interfere, stop protein synthesis, etc.

Problems- Haiti- ethnography- no compliance with drug regimens. (too far from the clinic, too poor, obligations from home, selling land to buy drugs, etc.) out of their control Individual illness indicative of larger social problems Behavioral/social-whole foods/ chipotle

Horizontal gene transfer- rate can change depending on selective pressure o Ex. E. coli- gene reservoir-they can have horizontal gene transfer with bad bacteria

Bacteria is very fluid and fast at adapting.. we only have vertical-bacteria has horizontal and vertical Penicillin-also cured syphilis Cell wall o Penicillin-interferes with the building of peptidoglycan. Causes cell to lyse o Rifampin-interferes with RNA/DNA synthesis Example of beta lactamase o Subgroup is penicillin mase Transcription- DNA -> RNA Translation- RNA -> amino acids Vat fermentation- rise of mass-producing of antibiotics. Switch to corn liquor to feed o 1. Low dosages of antibiotics help animals fight bacteria, save energy for growing o 2. Antibiotics help killing bacteria o Inoculate medium with pure culture, culture eats nutrients, turns nutrient medium into antibiotic o Isolated through centrifuge o