MCB 100 1st Edition Lecture 25Outline of Last Lecture I. Killing microbes with heatII. RefrigerationIII. FiltrationIV. RadiationV. Antiseptics, disinfectants, and sanitizing agents VI. Controlling growth of microorganisms using osmotic pressureVII. Antibiotics and antimicrobial drugs VIII. General mode of action of antibioticsIX. General classes of antibiotics based on specific modes of action Outline of Current Lecture I. Antibiotics that inhibit peptidoglycan biosynthesis II. Antibiotics that inhibit protein synthesis by bacterial ribosomesIII. Mechanisms of resistance to antibiotics seen in some bacteriaIV. Minimum inhibitory concentration (MIC)V. Therapeutic Index (T.I)VI. Antifungal, antihelminthic, and antiprotozoan drugs VII. Antiviral drugsCurrent LectureI. Antibiotics that inhibit peptidoglycan biosynthesisa. Ex. Penicillins and cephalosporinsb. Penicillin binding protein is a bacterial enzyme that forms the peptide bond that cross-links one amino acid side chain in the peptidoglycan to another peptide chains c. B-lactam drugs are competitive inhibitors of this enzymed. If synthesis of peptidoglycan is inhibited, the bacterial cell wall becomes weak and the bacteria may break open due to osmotic pressure e. Other examples: bacitracin (interferes with movement of peptidoglycan precursors through the cytoplasmic membrane to the wall; vancomycin interferes with the incorporation of NAG-NAM-peptide subunits into peptidoglycan II. Antibiotics that inhibit protein synthesis by bacterial ribosomesa. Aminoglycosides- bind to the 30S subunit of the 70S ribosome and cause the mRNA to be misread; cause ribosome to slip, sometimes moving 4 bases when changing from one codon to the next when it needs to move exactly 3 bases--> this causes the incorporation of incorrect amino acids into the growing protein chain 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. Tetracyclines- these block binding of tRNAs to ribosme- mRNA complexc. Chloramphenicol- blocks formation of peptide bonds between the amino acids of the growing protein chaind. Macrolides- stop movement of the ribosome down the mRNA (ex. Erythromycin)e. Quinolones- inhibit bacterial gyrase, which is involved in controlling the amount of supertwisting in DNA- blocking action of DNA gyrase blocks replicationf. Polymyxin- detergent-like drug that disrupts bacterial cell membranesg. Nucleotide analogs- block DNA replication and cause mutations h. In the future, antisense RNA may be introduced into human cells to inhibit the expression of specific genes that are found in microbial pathogens- need to make sure to safely introduce the antisense RNA into infected cells and to design sequences that will inhibit the pathogen but not harm the hosti. Antisense RNA- can block binding of a ribosome to a specific mRNA molecule II. Mechanisms of resistance to antibiotics seen in some bacteriaa. Bacteria may produce an enzyme that degrades or modifies the antibiotic. Genes for drug resistance factors are often located on plasmids. Drug resistance plasmids can often be transferred from species to speciesb. Altered pore proteins may slow diffusion of the drug into the bacterial cellc. The gene for the drug receptor may be mutated so the receptor no longer binds to the antibioticd. Resistant cells may alter their metabolism so they can by-pass the inhibited stepe. Resistant cells may acquire a gene for an active transporter protein that pumps the antibiotic out of the cell using energy from ATP. This type of resistance gene is often found on a plasmid or a transposonII. Minimum inhibitory concentration (MIC)a. MIC = lowest concentration of an antibiotic that will inhibit a pathogenb. Low MIC shows a potent drug for inhibiting a certain microorganismc. For a given drug, the MIC varies with the species and strain of the microorganism and the environmental conditions d. Kirby-Bauer test = standard lab test that can be used to predict the effectiveness of an antibiotics in the treatment of a patient against a particular pathogenII. Therapeutic Index (T.I)a. T.I is the ratio of the toxic dose divided by effective dose b. A higher T.I. = safer drug c. Low T.I. = there is a small margin for error as a physician tries to give the patient enough of the drug to kill the infectious microorganism but not so much that it hurts the patient II. Anti fungal, antihelminthic, and antiprotozoan drugs a. Antibiotics i. drugs that kill bacteriaii. Inhibit metabolic processes that happen in bacteria but not in mammalian cellsiii. Most are natural products made by a microorganism or are derivatives of natural productsb. Fungi, worms, and protozoa are all eukaryotic organismsi. They have 80S ribosomes (bacteria has 70S ribosomes) ii. Antibiotics that inhibit 70S ribosomes- tetracyclines, macrolides, and aminoglycosides, are not effective against them iii. Don’t have cell walls made of peptidoglycan so penicillins and cephalosporins are not effective against themiv. Drugs that ARE effective against eukaryotic microorganisms often have toxic side effects and a rather low therapeutic index1. Ex. Allyamines and azoles- miconazole--> inhibit ergosterol synthesis in fungi 2. Ex. Quinine inhibits metabolism in malaria parasites (protozoa) II. Antiviral drugsa. Viruses grow inside our cells and use metabolic pathways of our cells---> makes it more difficult to find substances that interfere with their life cycle that will not harm hostb. Antiviral compounds are usually specific inhibitors of certain enzymes that are found in virally infected cells that are not found in uninfected cellsc. Since there is a lot of diversity seen in the pathways used by viruses to replicate theirgenomic material, compounds that affect the reproduction or maturation of one type of virus may have no effect on other types of virusesd. Ex. HIV protease inhibitor = useful in treatment of AIDS but is very specific for a protein found in HIV infected cells (HIV protease)---> so it is not useful against the majority of other viruses because they don’t make protease enzyme similar to the one in HIV infected cellse. Ex. Acyclovir inhibits an enzyme that is involved in the cytoplasmic replication of the DNA genomes of some viruses such as herpes and chicken pox--> but it is not effective against RNA viruses/DNA viruses that don’t use a similar virally encoded kinase