Antibiotics and the bacterial cell

Sir Alexander Fleming

studied staphylococcus and realized there was a zone around the fungus where Staph couldn’t grow

Antimicrobial

drug to treat microbial infection

Antibiotic

antimicrobial drug naturally produced by a microorganism

Broad Spectrum

effective against a wide range of microorganisms, including most GM- and GM+ bacteria; can disrupt normal flora (ex. Chloramphenicol)

Narrow Spectrum

effective against a limited number of microorganisms; identification of microbe is helpful; not as disruptive to normal flora (ex: Polymyxin-B)

Bacteriostatic

stops the growth of the bacteria

Bacteriocidal

kills the bacteria

Antibiotic targets

1. Cell wall (peptidoglycan) synthesis

2. Nucleic acid synthesis (production of DNA or RNA)

3. Protein synthesis

4. Metabolic pathways (folate synthesis)

5. Cell membrane integrity (for Gm-)

Transpeptidase

a bacterial enzyme that crosslinks the peptidoglycan strands

Antibiotic targets: Prokaryotic ribosomes

-Bind to 30S or 50S subunit

-Can inhibit:

1. Docking of tRNAs

2. Movement of tRNAs through the ribosome

3. Formation of peptide bonds between amino acids

Antibiotic targets: Metabolic pathways and nucleic acid synthesis

-Inhibit folic acid metabolism: Important for purine synthesis and Eukaryotic cells do not synthesize folic acid

-Inhibit nucleic acid synthesis: Block DNA polymerase, block RNA polymerase, block enzymes involved in supercoiling DNA (DNA gyrase and Topisomerase IV)

Antibiotic targets: Bacterial Cell Membrane

-Bind to Lipid A (polymyxins) in the outer membrane (only effective against gram negative)

-often associated with toxic side effects: can bind other phospholipids

How can you choose the best antibiotic for an infection, and an effective concentration of that antibiotic?

antibiotic susceptibility tests

Minimum Inhibitory Concentration

the lowest concentration of an antimicrobial needed to prevent the growth of a particular bacteria in vitro

How is MIC measured

Kirby-Bauer test, E-test, Serial dilution test

Minimum Bactericidal Concentration

lowest concentration the will kill the bacteria

Kirby-Bauer Method

-zone of inhibition forms around disks that contain an effective antibiotic

-zone measured to determine if the bacteria is susceptible, intermediate, or resistant to each antibiotic.

E test

Uses paper strips. Each strip has a labeled gradient of an antibiotic.

How can you determine the MIC on an E test

The intersection of the elliptical zone of inhibition with the strip indicates the MIC for that antibiotic

3 general approaches to antibiotic resistance

1. Exclude the antibiotic from the cell: expel the antibiotic or prevent its entry

2. Alter the bacterial target: acquire a mutation that changes the amino acid sequence (and therefore the structure) of the target protein

3. Inactivate the antibiotic through an enzyme

Bacteriophage

Viruses that kill just bacteria. Each charge can only attack one species of bacteria.