Module 41Describe the desirable properties of antibiotics- toxic (high) - level at which it becomes toxic to cell- therapeutic (low) - level required for effective clinical treatmentUnderstand broad vs. narrow spectrum antibiotics- Broad- Work against a wide variety of bacteria - Narrow- Only active against a small group of Know what critical pathways in bacteria are inhibited by the antibiotics discussed in class-sulfanilamide - growth factor of p-amino-benzoic acid, precurser to folic acid => blocks nucleic acid synthesis (blocks enzymes)-isoniazid - growth factor of nicotinamide, an intermediate in the synthesis of mycolic acids by mycobacterium => blocks synthesis of mycolic acids (blocks part of cell wall) *widely used for TB treatment-quinolones - inhibitors of DNA gyrase, which is required for supercoiling of DNA => block DNA gyrase (block activity and bacterial cell division)Understand the mode of action by each of the antibiotic examples discussed in the lectureKnow how isoniazid and quinolones function to impede bacterial growth.Isoniazid- is a growth factor of nicotinamide which is an intermediate in the synthesis of mycolicacids by mycobacterium, synthesis of mycolic acids is blockedQuinolones- are inhibitors of DNA gyrase and is required for supercoiling of DNA, they bind to DNA gyrase and block activity, bacterial cell division is blockedDescribe the bacterial enzyme that is inhibited by β-lactam antibiotics and identify a generalizedchemical structure of a β-lactam antibiotic.- b lactams inhibit peptidoglycan synthesis- bacterial enzyme - penicillin GKnow the three classes of antibiotics that bind to bacterial ribosomes, and the example of each class1. Aminoglycoside antibiotics such as Kanamycin bind to 30s RNA subunit of bacterial ribosomes 2. Marcolide antibiotics such as erythromycin bind to the 50s subunit of bacterial ribosomes 3. Tetracyclines occur naturally, many semisynthetic derivatives Understand how an ionophore antibiotic such as daptomycin works to kill bacteria- ionophore -hole for ions- daptomycin- is a cycliv lipopeptide which is a long lipid chain at bottom that embeds intomembrane that aggregates and inserts into the cytoplasmic membrane- creates pores in membrane that result in de-energized membrane, PMF is lost and cell dies due to lack of energyComprehend the mechanisms of resistance of bacteria to antibiotics Know the mechanisms of resistance presented in lecture1. reduced permeability of the antibiotic - penicilin G cannot get into gram -2. inactivation of the antibiotic by a bacterial enzyme - b- lactomase to cut b lactam3. mutation in the antibiotic target - cannot bind cause target is mutated4. development of a metabolic bypass in a pathway5. efflux pump - making sure concentration of antibiotic is low at all times. Be able to differentiate the Etest result of an antibiotic resistant strain and antibiotic sensitive strain.- the sensitive strain will have clearing of bacteria until MIC- the resistant strain will have growth of bacterial colonies inside clearingDescribe why antibiotic resistant pathogens are becoming more prevalentList the examples of antibiotic resistant bacterial threats1. MRSA - skin pathogen that becomes invasive, problem in healthcare settings, type of b lactam2. VRE - enterococcus inhibits human intestional tract, most occur in hospitals3. Others - MDR -TB, CRE, clostridium difficle. antibiotic resistant but infections occur in patientstreated with antibioticsUnderstand the mechanism of resistance provided by MecA and NDM-1 Define selective pressure in the context of antibiotic resistancehas increased the prevalence of antibiotic resistant pathogens, especially in clinical studiesKnow what can be done to reduce the increase of antibiotic resistant bacteria in clinical settings1. reduce use of antibiotics2. increased development of new
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