Lectures 27 and 28 Antimicrobial Drugs bacteria Spectrum of activity Describe selective toxicity spectrum of activity and explain why most antibiotics are specific for Selective toxicity a drug that kills harmful microbes without damaging the host Broad spectrum effective against many species Narrow spectrum effective against few or a single species Drugs should affect microbial physiology that does not exist or is greatly Selective toxicity of antibiotics Affect only target organism modified in humans Peptidoglycan Differences in ribosome structure Biochemical pathways absent in humans Bactericidal antibiotics Kill the target organism Many drugs only affect growing cells Inhibitors of cell wall synthesis only effective if the organism is building a new cell wall Bacteriostatic antibiotics Prevent growth of an organism Cannot kill organism Immune system removes infection Name the microbes that produce most antibiotics Identify five modes of action of antimicrobial drugs Inhibition of cell wall synthesis penicillins cephalosporins bacitracin vancomycin Inhibition of protein synthesis chloramphenicol erythromycin tetracyclines streptomycin Inhibition of nucleic acid replication and transcription quinolones rifampin Injury to the plasma membrane polymyxin B Inhibition synthesis of essential metabolites sulfanilamide trimethoprim List the advantages of each of the following over penicillin semisynthetic penicillins cephalosporins and vancomycin Semisynthetic penicillins Extended spectrum Ampicillin can affect many gram negatives Cephalosporins Vancomycin 2nd 3rd and 4th generations are mosre effective against gram negatives Important last line against antibiotic resistant S aureus Explain why INH and ethambutol are antimycobacterial agents Isoniazid INH inhibits mycolic acid synthesis Ethambutol inhibits incorporation of mycolic acid Describe modes of action of aminoglycosides tetracyclines chloramphenicol macrolides polymyxin B bacitracin and neomycin rifamycins and quinolones Aminoglycosides Include streptomycin neomycin and gentamycin Broad spectrum Changes shape of 30S subunit Side effect hearing loss Inhibitors of cell wall synthesis Tetracyclines Broad spectrum Inhibitors of protein synthesis Interferes with tRNA attachment Chloramphenicol Broad spectrum Inhibitors of protein synthesis Binds 50S subunit and inhibits peptide bond formation Macrolides Gram positives Inhibitors of protein synthesis Binds 50S and prevents translocation Combined with bacitracin and neomycin in over the counter preparation Neosporin Injury to the plasma membrane Combine with Polymyxin B and Neomycin to make neosporin Combine with Polymyxin B and Bacitracin to make neosporin Polymyxin B Topical Bacitracin Neomycin Rifamycin Inhibitor of nucleic acid synthesis Inhibits RNA synthesis Antituberculosis Quinolones Ciprofloxacin Inhibits DNA gyrase Anti anthrax Urinary tract infections Inhibitor of nucleic acid synthesis Describe how sulfa drugs inhibit microbial growth Inhibit folic acid synthesis with a competitive or noncompetitive inhibitors Explain the modes of action of currently used antiviral drugs Protease inhibitors Indinavir HIV Inhibit attachment Influenza Inhibit uncoating Amantadine Influenza Oseltamivir Tamiflu neuraminidase inhibitor Interferons prevent spread of virus to new cells Viral hepatitis Describe two tests for microbial susceptibility to chemotherapeutic agents Kirby Bauer disk diffusion test Test strain sensitivity to multiple antibiotics Size of cleared zones reflects relative sensitivity E test Gradient of antibiotic in paper strip Determines MIC Drug must be above MIC in tissue in order to be effective Describe the mechanisms and causes of drug resistance A variety of mutations can lead to antibiotic resistance Mechanisms Enzymatic destruction of drug Prevention of penetration of drug Alteration of drug s target site Rapid ejection of the drug Resistance genes are often on plasmids or transposons that can be transferred between bacteria Misuse of antibiotics selects for resistance mutants Lecture 29 Microbial Diseases of the Skin and Eyes Describe the structure of the skin and mucous membranes and the ways pathogens can invade the skin Skin Dry Lysozyme hydrolyzes peptidoglycan Fatty acids inhibit some pathogens Defensins are antimicrobial peptides 1 Epidermis Stratus corneum and keratin thin outer portion a Keratin waterproofing protein b Stratus corneum outermost layer of the epidermis 2 Dermis inner relatively thick portion of the skin composed mainly of connective tissue microbes a Secretions perspiration and sebum contain nutrients salt inhibits i Perspiration provides moisture and some nutrients for microbial growth ii Sebum secreted by oil glands a mixture or lipids proteins and salts that prevents skin and hair from drying out b Portals of entry follicles and ducts 3 Subcutaneous layer the innermost layer of the skin underneath the dermis Mucous Membranes Line body cavities The epithelial cells are attached to an extracellular matrix Cells secrete mucous Some cells have cilia Provide examples of normal skin microbiota and state the general locations and ecological roles of its members Gram positive bacteria such as Staphylococcus Low GC gram Streptococcus Low GC gram Diptheroids coyneforms high GC gram Staphylococcus aureus Streptococcus Coagulase an enzyme clots fibrin in blood all pathogenic S aureus are coagulase positive Most pathogenic of the staphylococci Produce extracellular enzymes and toxins Cause folliculitis furuncles boils carbuncles toxemias occur when toxins enter the bloodstream scalded skin syndrome toxic shock syndrome Hemolysins beta alpha and gamma hemolysis Lyse red blood cells as well as almost any type of cell Classified into groups according to hemolytic enzymes and surface antigens Group A most important Groups B C and O Many virulence factors M protein extracellular enzymes and toxins M protein prevents the activation of the complement and allows the microbe to evade phagocytosis and killing by neutrophils M protein on the surface anti complement anti phagocytosis Cause impetigo isolated pustules erysipelas Erysipelas caused when S pyogenes infects the dermal layer of the skin the skin erupts into reddish patches with raised margins can cause sepsis Some yeasts Differentiate Staphylococci from Streptococci and name several skin infections caused by each Staphylococci gram low GC cocci in clusters Infections Folliculitis Infections of the hair
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