In this article we will discuss about the features and mechanisms of antimicrobial drugs.
Features of Antimicrobial Drugs:
Some of the features of antimicrobial drugs are given below:
(a) Antibiotics are biologically active against a large number of organisms even in extremely low concentration. It is interesting to observe that 0.000001 g/ml of penicillin G has a pronounced effect on bacteria sensitive to this antibiotic.
Therefore, the minimal inhibitory concentration (MIC) of an antibiotics effective against different microorganisms, or MIC of different microorganisms for a given microbe differs. MIC refers to the lowest concentration of drugs required to kill the microbial pathogen. It is also called minimal lethal concentration.
(b) These are very selective in posing toxicity i.e. they must kill or inhibit the pathogenic microbe without having harmful effect, or having least harm to the host. This is called selective toxicity. For example penicillin acts against Gram-positive bacteria (e.g. streptococci), while streptomycin acts against Gram-negative bacteria e.g. E. coli.
(c) The degree of selective toxicity is expressed in terms of therapeutic index which is the ratio of toxic dose to the therapeutic dose. The therapeutic dose is the drug level required for treatment of a particular infection, while the toxic dose is amount of drug at which it becomes too toxic to the host.
(d) The range of effectiveness of antimicrobial drugs varies. These may be narrow-spectrum drugs (effective only against a limited number of pathogens), or broad-spectrum drugs (effective against a large number of pathogenic microbes).
However, on the basis of groups of microorganisms, the antimicrobial drugs are also classified as antibacterial (effective against bacteria), antifungal (against fungi), anti-protozoan (against protozoan) and antiviral (against viruses).
(e) Antibiotics are secondary metabolites i.e. they are not required during the growth by microorganisms. Therefore, these accumulate either inside the cell or secreted outside the cell. Some of the antibiotics are volatile as well. In recent years, the natural molecule of the antibiotics are being chemically or biologically modified, and new ones being produced.
Such modified antibiotics are known as semisynthetic antibiotics e.g. ampicillin, methicillin, carbenicillin, etc. The semisynthetic antibiotics are more important as compared to natural antibiotics. Thus, the semisynthetic antibiotics are natural antibiotics that have been chemically modified by the addition of extra chemical group so that it could not be inactivated by pathogens.
(f) The potency of antibiotics is normally expressed in terms of units/ml or solution or in one milligram [U (units)/mg]. After the discovery of antibiotics it was found that 1 mg of streptomycin is equivalent to 1000 units. Now-a-days the antibiotic vials’ label shows the quantity expressed in terms of weight as well as activity. For example, 1 mg of the penicillin G (benzyl-penicillin) is equivalent to 1667 units.
Mechanism of Action of Antimicrobial Drugs:
After administration of antimicrobial drugs against a particular pathogen, a patient feels relief. This is due to killing of infectious microorganisms involved with a specific disease. It is interesting to know how does it act? The mechanism of action of each antimicrobial drug differs.
However, on the basis of their mode of action, it can be grouped as below:
(i) Inhibition in Synthesis of Bacterial Cell Wall:
Penicillins stop the synthesis of cell wall of Gram-positive bacteria that are synthesizing new peptidoglycan. It inhibits trans-peptide enzymes which are responsible for cross-linking of the polypeptide chain of the bacterial cell wall peptidoglycan. It also activates cell wall lytic enzymes. The other antibiotics that inhibit cell wall of bacteria are ampicillin, carbenicillin, methicillin, bacitracin, vancomycin, cephalosporin, etc.
(ii) Disruption of Cell Wall:
Polymyxin B binds to plasma membrane and disrupts its structure and properties of permeability.
(iii) Alteration in Membrane Function:
Gramicidin can alter the function of cell membrane. The dis-organisation of the state and function have been well noticed. It brings about changes in permeability of cell membrane and causes a quick loss of amino acids, minerals, phosphorus and nucleotides. Also it inhibits the energy metabolism bringing about alteration in permeability e.g. polymyxin, nystatin, etc.
(iv) Inhibition in Protein Synthesis:
Protein synthesis is the universal phenomenon of a living cell. However, some antibiotics inhibit protein synthesis of pathogenic microorganisms and act differently. Streptomycin binds to 30S subunit of the bacterial ribosome and cause misreading of mRNA and, therefore, inhibits protein synthesis at the final stage (i.e. during transport of aminoacyl tRNA to ribosomes.
However, it does not affect the initial stage i.e. activation of amino acids. Similar is the effect of gentamycin and tetracycline. Chloramphenicol and erythromycin bind to SOS ribosomal subunit and inhibits peptide chain formation and elongation respectively by inhibiting peptidyl transferase.
(v) Inhibition in Synthesis of Purines and Pyrimidines:
Mitomycin C inhibits the growth of many bacteria, protozoa, etc. and arrests the growth of tumour cells. The chromatophore of actinomycin is incorporated between DNA base pairs, whereas mitamycin blocks the synthesis of DNA without affecting RNA and protein synthesis. Rifampicin inhibits DNA-dependent RNA polymerase and, therefore, blocks protein synthesis.
(vi) Inhibition in Respiration:
Antimycins inhibit the growth of some fungi. This group of antibiotics inhibit oxidation of succinate. Valinomycin is active against Gram-positive bacteria and inhibits oxidative phosphorylation. Gramicidins are inhibitors of phosphorylation.
(vii) Antagonism of Metabolic Pathways:
There are some of the antibiotics that block the functioning of metabolic pathways through competitive inhibition of key enzymes. Such valuable drugs are known as antimetabolites.
For example sulfonamides (e.g. sulfonilamide, sulfamethoxazole and sulfacetamide) and other drugs inhibits folic acid metabolism through competing with p-amino-benzoic acid. Trimethoprim blocks tetrahydrofolate synthesis through inhibition of the enzyme dihydrofolate reductase. Isoniazid disrupts either pyridoxal or NAD metabolism and functioning.