EPI 390 Lecture 14Outline of Last Lecture I. The Goal of Medico-legal InvestigationsII. Osteoarthritic Skeletal ModificationsIII. Information gathered from Radial TuberosityIV. Complications with identifying RaceV. Protecting the Public HealthVI. Levels of PreventionVII. Public Health Intervention CampaignsVIII. Bridging Population and CasenessOutline of Current Lecture Guest Lecturer: #3 Dr. Julie WirthI. An Introduction to Microbes and AntimicrobialsII. Resistance in MicrobesIII. A History of AntimicrobialsIV. Antimicrobial MechanismV. Mechanisms of ResistanceVI. Examples of Multidrug ResistanceVII. An Introduction to BioterrorismVIII. The History of BioterrorismIX. AnthraxX. Classification of BioweaponsCurrent LectureI. An Introduction to Microbes and Antimicrobialsa. Definitionsi. Antibiotics and Antimicrobials – a molecule that inhibits the function of orkills microbes.ii. Antimicrobial resistance – the ability of a microbe to survive the exposureto an antimicrobial.1. Humans provide the selective pressure encouraging the rise of antimicrobial resistance by taking antimicrobials. This stress stress selects for microbes with the resistance trait.2. This resistance can occur in a variety of mechanisms.These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.b. Microbe structure – prokaryotes have a cell wall, which mammalian cells do not have.i. The cell wall has a structural role and acts as a barrier from many harmful substances in the environment (i.e. antibiotics or antimicrobials)c. Antimicrobial therapy has been used to fight infectious bacterial diseasesi. This therapy is one of the leading causes for the rise in life expectancy in the 20th Centuryii. Recently, though, diseases (i.e. wound infections, gonorrhea, tuberculosis, pneumonia, etc.) that were previously controlled by antimicrobials are now difficult to treat.1. The microbes have developed resistance to the common antibiotics.II. Resistance in Microbesa. Settings for Antimicrobial resistant infectionsi. Community – infections occur from going out with friends, and getting exposed to microbes in the environment.ii. Hospitals – Patients with weakened immune systems are at risk of catching infections from other patients.b. Multidrug resistance: many diseases have developed resistances to multiple antibioticsi. This has left doctors struggling to treat infections with limited or no effective antimicrobial options.ii. This has triggered a search for new antimicrobials to keep options of effective drugs are available.c. Characteristics exacerbating antimicrobial resistancei. Bacterial growth encourages the development of resistance.1. Because bacteria grow and replicate so quickly, the rate of mutation greatly increases.2. Usually the mutations are harmless, but sometimes they lead to resistance to antimicrobials, which quickly propagate under selective pressures.ii. Extensive overuse of antimicrobials has exacerbated the resistance problem.1. The overuse of antimicrobials in human and veterinary medicine, and in agriculture has created an environment that promotes resistance.III. A History of Antimicrobialsa. 1929 – The first antimicrobial was discoveredi. Sir Alexander Fleming left a plate of Staphylococcus aureus open and it became contaminated with a sporulating mold, Penicillium notatum.1. He noticed the bacteria struggled to grow next to the mold2. Penicillin was isolated from the mold, and became the first substance used as an antimicrobial.b. 1946 – penicillin became commercially available and where highly successful against S. aureus infections.i. Many infections were treated, and people were able to survive infections that would have killed them in the past.ii. It took S. aureus ~1.5 years after it was commercially available to developantibiotic resistance.1. Penecillinase is what binds to penicillin and deactivates it in resistant bacteria.c. 1959 – Realizing that penecillinase was the enzyme causing the resistance, researchers developed methicillin, a drug that doesn’t bind to penecillinase.i. 1961 – The first methicillin-resistant S. aureus isolates were foundii. Gentamicin and Vancomycin were also developed1. Gentamicin alters the bacterial ribosome; vancomycin inhibits the incorporation of some peptide units into the cell wall.2. The bacteria always rapidly developed resistance to the new antimicrobials.IV. Antimicrobial Mechanisma. Penicillin – inhibits an enzyme that links molecules in some bacterial cell walls.i. The poorly constructed cell wall causes the bacteria to die.b. Antimicrobials work by inhibiting an essential process in bacterial growthi. i.e. cell wall synthesis, protein synthesis, ribosome function, etc.ii. Once the antimicrobial is introduced, bacteria don’t grow as well, die, or survive to pass on the resistance gene.V. Mechanisms of Resistancea. Resistance arises when a microbe population previously sensitive to an antimicrobial develops a resistance to the inhibition effect, rendering the antimicrobial ineffective.i. Most bacterial infections in hospitals (~70%) are now resistant to at least one commonly used antimicrobial treatment.b. Mechanisms:i. Enzymatic inactivation of the antimicrobialii. An existing enzyme is modified to react with the antimicrobial so that it no longer affects the bacteriaiii. Altering the antibiotic target sitec. Acquiring Resistance – for bacteria to survive the introduction of antimicrobials, they either develop a mutation coding for resistance, or inherit the resistance gene from a neighbouring bacterium.i. Genes coding for antimicrobial resistance can be transmitted from one bacterium to another via plasmids. A plasmid with multiple resistance genes is called multiresistant or a superbug/super bacteria.d. Antibiotic resistant genes can block antimicrobial mechanisms in one of 3 ways.i. Coding for an enzyme that degrades the antibiotic.ii. Coding for a gene that alters the enzyme, inhibiting its function.iii. Coding for a gene that creates an efflux pump in the bacterial plasma membrane. The pump removes the antibiotic from the cell before it can cause harm.e. Natural selection aids in the rise of antimicrobial resistance.i. In a mixed population, the resistant strains are often at a disadvantage, competitively. However, when an antimicrobial is introduced to the population, the susceptible microbes will die off.1. Without