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How Antibiotics Kill? Mechanism of Action of Various Antibiotics
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
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
Some antibiotics bind to the peptidyl transferase component of 50S ribosome, blocking peptide elongation. Example include Chloramphenicol
  • Inhibitors of amino acid-acyl-tRNA Complex binding
It includes those antibiotics which bind to 50S subunit in such a way that they block the binding of amino acid-acyl-tRNA complex and hence inhibit peptidyl transferase action and hence peptide elongation. Example Clindamycin.
  • Reverible Binders
These bind to 50S subunit in a reversible manner to temporarily block peptide elongation (hence these are bacteriostatic). Example: Macrolides like Azithromycin, Erythromycin, Roxithromycin, Clarithromycin etc

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 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.
  • DNA damagers
This class of antibiotics are metabolized in the microbial cell to generate toxic and highly active byproducts that attack ribosomal proteins,DNA, respiration, pyruvate metabollism and other macromolecules within the cell.
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.

Following is a diagrammatic summary of the mechanisms of action of various antibiotics:
[Image: antibiotic_targets_web.gif]

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!
Sunil Nagpal
MS(Research) Scholar, IIT Delhi (Alumnus)
Advisor for the Biotech Students portal (
Computational Researcher in BioSciences at a leading MNC

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Quinolone resistance and CF

Despite the wide variety of antibiotics available, with their multiple methods of action, resistance to antibiotics is a serious public health issue. Cystic Fibrosis (CF) patients represent a cohort who are dependent on effective antibiotic treatment. Quinolones are an example of a broad spectrum antibiotic class used widely in treatment of infections in CF patients as well as in other groups.

Quinolone antibiotics target both DNA gyrase, composed of the subunits GyrA and GyrB and DNA topoisomerase IV, composed of ParC and ParE. Many pathogenic bacteria including Pseudomonas aeruginosa have developed resistance to quinolones due to the widespread use of these antibiotics. Pseudomonas aeruginosa, a Gram-negative bacterium, is a major pathogen of CF patients and a significant cause of death in these patients.

Studies on clinical samples have addressed the major mechanisms of resistance to quinolones and have identified mutations in the gyrA gene as being the most common, most importantly at the highly conserved position 83 of GyrA (serine or threonine). Mutations in GyrB and ParE have also been shown to contribute to resistance. Interestingly however, in terms of CF, a review from the University of Ottowa comparing resistance to quinolones between samples from CF patients and those from non-CF patients with acute infections revealed some differences in non-gyrase resistance-conferring mutations. These focused on genes encoding pumps responsible for influx or efflux of drugs and can therefore affect the intracellular concentration of drugs including quinolones. In terms of Pseudomonas aeruginosa, two efflux pumps, MexAB-OprM and MexCD-OprJ are implicated in quinolone resistance. Genes named mexR and nfxB respectively encode repressors of these two pumps. The review revealed that in CF samples mutations of nfxB were present in 57% of samples; none carried mutations in mexR or in the topoisomerase gene parC. However, nfxB mutations were relatively uncommon in non-CF samples, while parC and mexR mutations were found in 48% and 33% of cases respectively. This suggests that environment-specific mechanisms are at work in Pseudomonas aeruginosa quinolone resistance, for example related to biofilm growth in CF patients, effective drug does or epistasis. Thus local environmental differences in mechanisms of drug resistance need to be considered in devising choice of drug treatment in CF and other diseases.


WONG, A. and KASSEN, R., 2011. Parallel evolution and local differentiation in quinolone resistance in Pseudomonas aeruginosa. Microbiology (Reading, England), 157, pp. 937-944

WONG, A., RODRIGUE, N. and KASSEN, R., 2012. Genomics of adaptation during experimental evolution of the opportunistic pathogen Pseudomonas aeruginosa. Plos Genetics, 8(9), pp. e1002928-e1002928

MAEDA, Y. et al., 2011. Molecular characterization and phylogenetic analysis of quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC and parE gene loci in viridans group streptococci isolated from adult patients with cystic fibrosis. The Journal of antimicrobial chemotherapy, 66(3), pp. 476-486
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Superbugs (or multi-drug-resistant bacteria) have remained a headache for the scientific and healthcare industry. A Super-bug stands resistant to all possible antibiotics. The situation arises because of following factors:
a) Misuse of antibiotics: Using them when not needed, and not completing the dosage/course of medication.
b) The more types of antibiotics one get exposed to, the greater are the chances of developing super-bug vulnerability.

It is thus very crucial that a judicial choice as well as use of the antibiotics is made.
Sunil Nagpal
MS(Research) Scholar, IIT Delhi (Alumnus)
Advisor for the Biotech Students portal (
Computational Researcher in BioSciences at a leading MNC

Suggested Reads:
Top Biotech Companies | Top places to work
Indian Biotech Companies and Job Openings
Aiming a PhD in Top Grad School? | These are the Important Points to Consider
Careers in Biotechnology | A list of various Options
Biotechnology Competitive Exams in India
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