O'Donnell Antibiotics + Bacteria

Zone of Inhibition

The area around an antimicrobial agent where microorganisms are unable to grow

Antimicrobial Drug

Drug to treat microbial infection

Antibiotic

Antimicrobial drug naturally produced by a microorganism

Broad Spectrum Antibiotic

Effectuve against a wide range of microorganisms, including most gram negative and gram positive bacteria

• Can disrupt normal flora

• Ex: Chloramphenicol

Narrow Spectrum Antibiotic

Effective against a limited number of microorganisms

• Identification of microbe 

  • Usually bettwe on gram positive OR gram negative

• Not as dirsruptive to normal flora

• Ex. Polymyxin-B

Bacteriostatic Antibiotic

Stops the growth of the bacteria

Bactericidal Antibiotic

Kills the bacteria

Antibiotic Targets

• Cell wall (peptidoglycan synthesis)

• Nucleic acid synthesis

• Cell membrane integrity

• Metabolic pathways (folate synthesis)

• Protein synthesis

Transpeptidase

A bacterial enzyme that crosslinks peptidoglycan strands

What type of antibiotics target cell wall synthesis?

Bacticidal antibiotics

• Penicillin

• Vancomycin

How does penicillin target cell wall synthesis?

Inhibits transpeptidase

How does vancomycin target cell wall synthesis?

Binds to amino acid side chain and blocks transpeptidase binding

How can antibiotics target protein synthesis?

Bind to 30S or 50S subunit of prokaryotic ribosomes

Can inhibit:

• Docking of tRNAs

• Movement of tRNAs through the ribosome

• Formation of peptide bonds between amino acids

Can be bactericidal or bacteriostatic

How can antibiotics target metabolic pathways?

Inhibition of folic acid metabolism

• Human cells don’t make folic acid, while bacteria do

• Important for purine (A + G) synthesis

• Without folic acid, bacteria can’t make nucleotides

What type of antibiotics target bacterial metabolism pathways?

Bacteriostatic antibiotics

• Sulfonamides

• Trimethoprim

How can antibiotics target nucleic acid synthesis?

• Block DNA replication

• Block RNA polymerase

• Block enzymes involved in supercoiling DNA

What type of antibiotics target nucleic acid synthesis?

Bacteriostatic antibiotics

• Rifampin

• Metronidazole

• Quinolones

How can antibiotics target bacterial cell membrane integrity?

Bind to Lipid A (toxic part of LPS)

• Effective against gram negative bacteria

• Often associated with toxic side effects

  • Can bind other phospholipids

What type of antibiotics target bacterial cell membrane integrity?

Bactericidal antibiotics

• Polymyxins

Minimum Inhibitory Concentration (MIC)

The lowest concentration of an antimicrobial needed to prevent the growth of a particular bacteria in vitro (in a dish/lab)

How can the minimum inhibitory concentration be measured?

• Kirby-Bauer test

• Serial dilution test

• E-test

Minimum Bactericidal Concentration (MBC)

The lowest concentration of an antimicrobial needed to kill the bacteria

Kirby-Bauer method of measuring MIC

• Paper disks are soaked in different antibiotics

• A pure culture of the bacteria is grown on the plate

• A zone of inhibition forms around disks that contain an effective antibiotis

  • Large ring = potent antibiotic

• The zone is measured and the bacteria is determined to be S (susceptible), I (intermediate), or R (resistant) for each antibiotic

  • S = works very well

  • I = could work at high doses

  • R = does not work

Serial Dilution Test for MIC

Several test tubes are filled with various concentrations of antibiotics and the same amount of bacteria, including controls with only bacteria or only antibiotic

After a set amount of time, bacteria will grow in some of the test tubes. The lowest concentration of antibiotic without visible growth is the MIC

This test is performed for multiple antibiotics, which are assigned S (susceptible), I (intermediate), or R (resistant). This information can be used to pick the best antibiotic for the patient

E-test for MIC

Similar to Kirby-Bauer, but uses test strips containing a gradient of antibiotic

The intersection of the zone of inhibition with the strip indicates the MIC

Three main approaches to antibiotic resistance

• Exclude the antibiotic from the cell

  • Expel the antibiotic or prevent its entry

  • Often through efflux pumps

• Alter the bacterial target

  • Acquire a mutation that changes the amino acid sequence and structure of the target protein

  • Ex. Mutated transpeptidase

• Inactivate the antibiotic through an enzyme

  • Ex. β-lactamase cleaves penicillin

Bacteriophage

Virus that kills bacteria

Phage Therapy

Uses types of viruses called bacteriophages to target and kill bacteria

• Different types of phages attack specific bacteria