06-12-2013, 11:46 PM
(This post was last modified: 06-13-2013, 01:40 AM by Administrator.)
Today, there exist a variety of antibiotics for a variety of pathogenic micro-organisms. Each antibiotics is peculiar in it's traits of spectrum, shelf-life, half-life, toxicity, dispersal and mechanism of action. Despite the plethora of antibiotics already existing today, the scientists are always in a pursuit to discover more and better kinds of antibiotics, which might act fast and effect more for a longer period of time, without any resistance from the target microbe. In-fact, the resistance developed in the target microbe towards the existing antiobiotic after a prolonged use, is actually what triggers the research towards developing new antibiotics. But no matter what class or kind of antibiotics exists or is discovered, all of them operate by one of the following mechanisms:
1). Inhibition of cell wall synthesis
2). Inhibition of protein synthesis
3). Inhibition of membrane function
4). Disruption of Metabolism
5). Inhibition of nucleic acid synthesis
The Cell Wall Synthesis Inhibitors
It includes those antibiotics which inhibit the synthesis of microbial cell wall (mostly bacteria, which possess cell walls). There are three mechanisms of inhibition of cell wall, and hence three classes of antibiotics in this regard:
a. Inhibition of peptidoglycan (the structural unit of bacterial cell wall) synthesis
b. Inhibitors/Disruptors of peptidoglycan cross-linkage (making the structural framework of bacterial cell wall)
c. Disruptors of Precursor Movement
The inhibitors of Protein Synthesis
a. Ribosome Subunit Binders
Bacterial ribosomes have 30S and 50S subunits. Both of which are involved in different steps of translation. There are classes of antibiotics which tend to bind to these subunits reversibly/irreversibly, blocking the assembly of ribosomes, or inhibiting elongation and hence translation:
(i) 30S Binders
Aminoglycosides like Gentamicin, Amikacin, Tobramycin etc come into this category which bind irreversibly to 30S subunit of ribosomes.
(ii) 50S Binders
50S binders can bind to 50S subunit in following ways:
b. t-RNA binding blockers
This class of antibiotics block the binding of tRNA to 30S ribosome-mRNA complex. Tetracyclines like doxycycline, minocycline, plain tetracycline etc.
The Disruptors of Membrane Function
The Disruptors of Metabolism (Folate Pathway Inhibitors)
The inhibitors of Nucleic Acid Synthesis
Depending upon the target Nucleic Acid, the antibiotics may be:
a. DNA Inhibitors
The antibiotics may act on the DNA synthesis process of the microbes by:
Examples: Metronidazole, and furanes like Nitrofurantoin.
b. RNA inhibitors
Following is a diagrammatic summary of the mechanisms of action of various antibiotics:
1). Inhibition of cell wall synthesis
2). Inhibition of protein synthesis
3). Inhibition of membrane function
4). Disruption of Metabolism
5). Inhibition of nucleic acid synthesis
The Cell Wall Synthesis Inhibitors
It includes those antibiotics which inhibit the synthesis of microbial cell wall (mostly bacteria, which possess cell walls). There are three mechanisms of inhibition of cell wall, and hence three classes of antibiotics in this regard:
a. Inhibition of peptidoglycan (the structural unit of bacterial cell wall) synthesis
Beta-Lactams is the class of antibiotics that act by this mechanism. Examples of antibiotics in this class are Penicillins (Ampicillin, Amoxicillin, Methicillin etc) , Cephalosporins, Monobactams, Carbapenems etc.
b. Inhibitors/Disruptors of peptidoglycan cross-linkage (making the structural framework of bacterial cell wall)
Glycopeptide class of antibiotics act by this mechanism. Most common example includes Vancomycin. Other are teicoplanin, telavancin, bleomycin, ramoplanin etc
c. Disruptors of Precursor Movement
This class of antibiotics block the movement of precursors required for peptidoglycan. Cyclic polypeptides like Bacitracin include such antibiotics. They are mostly used as ointments (topical use) because of their toxicity and poor bioavailability when taken through oral route.
The inhibitors of Protein Synthesis
It includes those antibiotics which inhibit the synthesis of proteins/enzymes vital for normal functioning of microbial cells. Since translation (protein synthesis) has numerous steps and components involved, there are almost equal number of mechanism of action of antibiotics as mentioned below:
a. Ribosome Subunit Binders
Bacterial ribosomes have 30S and 50S subunits. Both of which are involved in different steps of translation. There are classes of antibiotics which tend to bind to these subunits reversibly/irreversibly, blocking the assembly of ribosomes, or inhibiting elongation and hence translation:
(i) 30S Binders
Aminoglycosides like Gentamicin, Amikacin, Tobramycin etc come into this category which bind irreversibly to 30S subunit of ribosomes.
(ii) 50S Binders
50S binders can bind to 50S subunit in following ways:
- Binding to peptidyl transferase
- Inhibitors of amino acid-acyl-tRNA Complex binding
- Reverible Binders
b. t-RNA binding blockers
This class of antibiotics block the binding of tRNA to 30S ribosome-mRNA complex. Tetracyclines like doxycycline, minocycline, plain tetracycline etc.
The Disruptors of Membrane Function
There are the class of antibiotics that render the microbial cell membranes disfunctional by inducing random pores by detergent like activity. This leads to the disruption of osmotic balance causing leakage of cellular molecules, inhibition of respiration and incr eased water uptake leading to cell death. Gram-positive bacteria possessing a thick cell wall are naturally resistant to such antibiotics.
Example: Lipopeptides like Polymyxins belong to this call of antibiotics.The Disruptors of Metabolism (Folate Pathway Inhibitors)
This class of antibiotics inhibit the pathway responsible for the synthesis of folic acid which is essential for the synthesis of adenine and thymine (important nucleic acids for DNA and RNA synthesis; thymine is not required for RNA though, but required for DNA). And, since humans donot synthesize folic acid, so these antibiotics donot have an inhibitory toxic effect on humans.
The folic acid synthesis inhibition can take place by:
a. Inhibition of the enzyme dihydrofolate reductase required for folic acid synthesis. Example: Trimethoprim/Sulfamethoxazole acts by inhibiting dihydrofolate reductase.
b. Substrate competition with p-aminobenzoic acid (PABA)thereby preventing synthesis of folic acid. Example: Sulfonamides & Dapsone.
The folic acid synthesis inhibition can take place by:
a. Inhibition of the enzyme dihydrofolate reductase required for folic acid synthesis. Example: Trimethoprim/Sulfamethoxazole acts by inhibiting dihydrofolate reductase.
b. Substrate competition with p-aminobenzoic acid (PABA)thereby preventing synthesis of folic acid. Example: Sulfonamides & Dapsone.
The inhibitors of Nucleic Acid Synthesis
Depending upon the target Nucleic Acid, the antibiotics may be:
a. DNA Inhibitors
The antibiotics may act on the DNA synthesis process of the microbes by:
- Inhibiting DNA gyrases
DNA gyrases (Type II Topoisomerases) are responsible for relieving the positive supercoils in the DNA (or introducing negative supercoils) ahead of the moving DNA polymerase, thereby enabling the availability of relaxed DNA strands for continuation of replication, as well as the compaction (negative supercoiling) of the large strands of newly synthesized DNA to pack them in the bacterial cell. Some antibiotics form a stable complex with these DNA gyrases, thereby inhibiting the DNA replication.
Example: Quinolones like Cinoxacin, Ciprofloxacin, Levofloxacin, Norfloxacin, Ofloxacin act by this way.
Example: Quinolones like Cinoxacin, Ciprofloxacin, Levofloxacin, Norfloxacin, Ofloxacin act by this way.
- DNA damagers
Examples: Metronidazole, and furanes like Nitrofurantoin.
b. RNA inhibitors
This class of antibiotics block the initiation and thus the synthesis of RNA in microbial cells.
Example: Rifampin and Rifabutin which bind toDNA-dependent RNA polymerase, thereby inhibiting the initiation of transcription.
Example: Rifampin and Rifabutin which bind toDNA-dependent RNA polymerase, thereby inhibiting the initiation of transcription.
Following is a diagrammatic summary of the mechanisms of action of various antibiotics:
So, there might exist numerous antibiotics in the market today, most of them act in one of the above described ways. I hope the next time you are prescribed an antibiotic for an infection, you should know the mechanism of it's action!