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What are the five basic mechanism of antibiotic action?
- 1. Peptidoglycan inhibition.
- 2. Protein synthesis inhibition.
- 3. DNA replication inhibition.
- 4. Folic Acid synthesis inhibition.
- 5. Lipid biosynthesis inhibition.
What is Penicillin?
Inhibits transpeptidases, the enzymes that catalyze the final cross-linking step in synthesis of peptidoglycan.
What is Kanamycin?
Binds irreversibly to the 30S subunit of bacterial ribosomes, and block the initiation of protein synthesis.
What is Ciprofloxacin?
Inhibits DNA replication by attacking bacterial DNA gyrase or topoisomerase 4.
What are sulfonamides?
Compete with para-aminobenzoic acid (PABA), thereby preventing the synthesis of the folic acid required by certain micororganisms.
What is Platensimyscin?
A selectively inhibiting antibiotic that acts agains cellular lipid biosynthesis.
What are the major classes of antibiotics that interfere with bacterial cell wall synthesis and how do they act?
B-lactam antibiotica. Inhibit transpeptidases (PBPs), the enzymes that catalyze the final crosslinkingstep in the synthesis of peptidoglycan
bacitracina. Interferes with dephosphorylation of lipid carrier responsible for movingpeptidoglycan subunit across cell membrane.
Glycopeptides. Inhibits cell wall synthesis by sterically interfering with formation of bridgesbetween peptidoglycan chains.
Isoniazid. Inhibit biosynthesis of cell wall mycolic acids, thereby making themycobacteria susceptible to reactive oxygen radicals and otherenvironmental factors.
How can bacteria use to develop resistance to beta-lactam antibiotic?
- hydrolysis of the antibiotic by β -lactamases (both gram positive and gramnegative)
- fails to bind to PBPs (both gram positive and gram negative)
- fails to cross membrane (only gram negative organisms)
Describe vancomycin resistance in Enterococcus.
There are two genes of interest in this type of resistance.
1. VanS:likely senses vancomycin in the environment.
- 2. VanR: when phosphorylated by VanS, activates transcription of othergenes, the organism synthesizes depsipeptides made by vanA. Whenthese peptides added to the building peptidoglycan moiety, bindglycopeptide antibiotics with decreased efficiency
- a)VanH, A,X,Y
How does Isoniazid act?
- Isoniazid believed to inhibit biosynthesis of cell wall mycolic acids, therebymaking the mycobacteria susceptible to reactive oxygen radicals and otherenvironmental factors.
- Activation of INH requires the enzyme catalase-peroxidase (KatG) and anelectron sink (hydrogen peroxide)
- KatG is the only enzyme capable of activating INH and therefore KatGmutant strains of M. tuberculosis are INH resistant
- However, KatG is not the only “player” involved in INH susceptibility orresistance. Depicted on the next page is a schematic diagram of other M.tuberculosis factors that are involved in resistance/susceptibility to INH.
What is the difference between bactericidal and bacteriostatic?
Bactericidal: kill bacteria directly
Bacteriostatic: Prevent bacteria from growing
What does minimal inhibitory concentration mean?
the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation.
Where do the polymyxins act?
Alters bacterial cell membranes.
What groups of antibiotics inhibit bacterial protein synthesis?
Discuss resistance to tetracycline.
1. Efflux of drug : drugs is rapidly expelled from resistant cells.
2. Ribosomal protection: No binding of tetracycline to ribosome because ribosome structure has been modified.
What is the difference in the site of action of quinolones and rifampin? Descibe the development of resistance to the agents.
i. Target1.DNA gyrase or topoisomerase IV
- ii. Resistance
- 1. Nosocomially-derived resistant isolates have acquired resistance viadecreased permeability.
- 2.Mutations in genes encoding DNA gyrase
i. Target1. DNA-dependent RNA polymerase
- ii. Resistance
- 1. Mutation in the chromosomal
What is a metabolic inhibitor? How do they act? Give and example.
a. These antimetabolites that interfere with normal synthesis or function of ametabolite in the cell.
What is a fatty acid biosynthesis inhibitor that is effective against MRSA/VISA?
a. It inhibits FAS2 II machinery.
i.Fab F/B are elongation condensing enzymes which are essential components
What are the differences between microbes and humans?
a. Faster metabolic rate
b.Rapid generation time
c.More versatile in use of energy sources and use of alternative electron acceptors.
d.More Diversity wiht respect to completeness of their biosynthetic pathways.
e.Streamlined methods of assembly
- i.DNA replication
- ii.RNA transcription
- iii.Protein translation
f.Unique materials (eg. LPS, merein, toxins, pigments)
What are the phases of bacterial growth?
What are the positives and negatives of oxygen respiration?
a. Aerobic respiration allows organisms to proliferate in the presence of oxygen;however, cells must have enzymes to deal with reactive oxygen species.
How are nutrients take up by bacteria?
i.differs from active transport in that substrate appears inside the cell in achemically modified form (eg. phosphate addition)
What are some physical factors involved in growth? (temp and pH)
Good metals: how do bacteria regulate iron uptake and what are the players involved?
i.Produce siderophores to scavenge iron
How do bacteria move: chemotaxis and twitching motility.
- i.Positive-in direction of nutrients (Swiming)
ii.Negative-in opposite direction of repellants (tumbling)
- b.Twitching mobility
- i.Pillus mediated movement
What is sporulation and why do organisms sporulate?
a.Formation of a genetic time capsle that can survive until conditions are correct, thenit can be triggered to germinate into the parent organism.
What is feedback inhibition, attenuation, and repression?
i.Mechanism by which biosynthetic and catabolic pathways regulate themselves.
i.The effective regulation of the biosynthesis of amino acids is of vitalimportance to the cell.
- i.Down regulates genes
Poop to power generation: microbial fuel cells (MFC).
a.Geobacter bacteria growing on anode an metabolize acetate and produce H2 gaswhich can be harnessed for fuel.