Modes and mechanism of action of antibiotics

MODES/MECHANISM OF ACTION
Antibiotics work through many modes or mechanisms of action that disrupt the
structure and/or function of the bacteria. The structure of a typical bacteria will
have a plasma membrane and a cell wall. All bacteria will have their DNA in the
form of a single circular chromosome. Within the bacteria cell DNA is replicated
for cell division (binary fission), DNA is transcribed into mRNA that will travel
to ribosomes where it gets translated into proteins. Let's look at some modes of
action that antibiotics use to combat bacteria.
There are 5 basic mechanisms or "modes of action" used by antibiotics:
1. Inhibition of Cell Wall Synthesis
2. Inhibition of Protein Synthesis
3. Interference with Membrane Functionality
4. Inhibition of Nucleic Acid Synthesis
5. Inhibition of Metabolic Pathways
1. INHIBITION OF CEL WALL SYNTHESIS
The most popular mode of action used by antibiotics is inhibition of cell wall
synthesis. There are 4 Classes of antibiotics that utilize this mode of action.
1. Beta-Lactams
2. Vanomycin
3. Bacitricin
4. Antimycobacterial Agents
Each of these classes of antibiotics goes about inhibiting cell wall synthesis in
slightly different ways.
 Beta-Lactams (like penicillin, ampicillin and amoxicillin) will inhibit the
production of peptidoglycan, which is a vital component of the bacterial
cell wall.
 Penicillin acts on the cell walls of Gram-positive bacteria. They
prevent peptidoglycans from forming. Peptidoglycans are
the major component of the cell wall, so without peptidoglycan,
the cell wall cannot form. This causes the bacterium to swell
and burst.
 Vancomycin will weaken the structural integrity of the cell wall by
disrupting peptidoglycan's ability to build cross-links.
 Bacitracin functions to block the precursors that are needed to form
peptidoglycan.
 Antimycobacterial agents disrupt mycolic acid or arabinoglycan synthesis
2. INHIBITION OF PROTEIN SYNTHESIS
The second most popular mode of action used by antibiotics is inhibition of
protein synthesis (translation). In bacteria cells, tRNA must bind to the 30S
ribosome-mRNA complex (b-static) in order for protein synthesis to occur.
One way in which antibiotics are able to inhibit protein synthesis is to target
this complex in one way or another.
There are 2 Classes of antibiotics that utilize this mode of action.
 Aminoglycosides are a class of antibiotics that inhibit protein synthesis by
irreversibly binding to the 30S ribosomal proteins so the complex cannot
form.
 Tetracyclines are a class of antibiotics that prevents tRNA from binding to
the 30S ribosome-mRNA complex
Another way antibiotics use to inhibit protein synthesis in bacteria is to disrupt
the 50S Ribosome Site. The bacterial ribosome includes a 30S subunit and a 50S
subunit. During the elongation phase of translation, both the 30S and 50S subunits
move along the mRNA template as tRNA adds the appropriate amino acids to the
growing polypeptide chain.
 Chloramphenicol is a class of antibiotics that attaches to the 50S ribosomal
subunit and effectively blocks the elongation.
 Macrolides like erythromycin will reversibly bind to the 50S ribosomal
subunit, blocking peptide elongation)
 Clindamycin ---> Binds 50S ribosome, blocks peptide elongation; Inhibits
peptidyl transferase by interfering with binding of amino acid-acyl-tRNA
complex
3. INTERFERENCE WITH MEMBRANE FUNCTIONALITY
Another mode of action antibiotics use is alteration of the cell membrane.
 Polymyxins change the membrane's permeability by altering its chemical
properties.
 Bacitracin includes topical antibiotics like neosporin. These antibiotics
disrupt the cytoplasmic membranes of bacteria.
4. INHIBITION OF NUCLEIC ACID SYNTHESIS
Inhibition of Nucleic Acid (DNA) Synthesis
1. Quinolones inhibit DNA topoisomerases that are needed to uncoil DNA for
DNA replication.
2. Metronidazole acts as a cytotoxin which disrupts the synthesis of DNA
Inhibition of Nucleic Acid (RNA) Synthesis
1. Rifampin is a class of antibiotics that binds to DNA-dependent RNA
polymerase
2. Bacitracin inhibits the process of mRNA transcription
A commonly-prescribed antibiotic that works as an inhibitor of DNA synthesis in
bacteria is Cipro. Cipro is in the quinolone class of antibiotics and is sometimes
used when an initial course of antibiotics fails to knock-down a bacterial
infection.
5. INHIBITION OF METABOLIC PATHWAYS
The final mode of action we will discuss is the inihibition of metabolic pathways.
This mode of action is sometimes called "antimetabolite activity."
1. Sulfonamides & Dapsone function as competitive inhibitors of p-
aminobenzoic acid (PABA) which is required for the synthesis of folic acid.
These antibiotics are commonly called "sulfa drugs" and include the
antibiotic bacteria.