Bacterial specific targets

1, cell wall

Antibiotics that target the cell wall:

penicillin G, ampicillin, methicillin, cephalosporins, vancomycin, clavulanic acid

2, DNA

Topoisomerase unique to bac which control the structure of DNA.

Ciprofloxacin: a DNA structure inhibiting drug.

3, RNA polymerase

Rifampin RNA polymerase inhibitor that recognize bacteria's RNA over ours.

4, Metabolic enzymes that are required for building the DNA

Sulfonamide inhibit from PABA to DHFA

Trimethoprim inhibit from DHFA to THFA, DHFA and THFA are critical in methyl transfer rxn during synthesis of thymidine.

We don't have PABA. it's unique to bacteria

5, Protein synthesis;

prokaryotic ribosome is different

Chloramphenicol

Erythromycin

Tetracycline

Aminoclycoside

MIC= minimum [] that stop the bac

MBC= minimum [] that kills the bac

2 modes of action of antibiotic

1: bactericidal

2: bacteriostatic

(can be lethal to immunosupressed patient)

Antagonistic effects of bac-static and bac-cidal drug

won't work

Mechanisms of drug resistance

1, Mutation

the drug sensitive ones are killed while the resistant, mutated ones survive and still divide.

2, Recombination

Bac A transfer resistant genes to Bac B

Acquisition of multi-drug resistance

happen by combination of resistant plasmid transfer units to create a large plasmid unit that has mutiple resistance.

created by pt receiving many kinds of antibiotics.

Pros & Cons of Combination therapy

less mutation chance

chance for developing combination drug resistance

Synergistic mechanism of action of 2 antibiotics

  protein synthesis inhibitor couple with cell wall inhibitor.

eg: Aminoglycoside

Penicillin

inhibit crosslinking of peptidoglycan chains

Transeptidase crosslink pentopeptide between D alanine and glycine

PBP (penicillin binding protein)

gets inactivated once bound to penicillin.

when it's inactivated, cell lysis occur.

it's a protein target for penicillin

PBP interact with beta lactam ring of penicillin

Bacteria has beta lactamase to degrade penicillin.

Beta lactamase opens up beta lactam ring, result in penicilloic acid (penicillin allergy)

Amidase

an enzyme that cleave and release R chains of penicillin, then you replace with another R chain to make synthetic penicillin.

This enzyme broden the spectrum of drug.

Penicillin subgroup:

naficillins: staphycoccal

ampicillins: both gram +/-, it's smaller than penicillin to cross through porin of gram - bac.

Gram + bac

thick cell wall with PBP 

few beta-lactamase

Gram - bac

thin cell wall

much smaller target porins

lots of beta-lactamases