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Antibiotics - The Microbial Defense Weapons

BY: Sandhya Anand | Category: Healthcare | Submitted: 2011-02-19 08:44:34
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Article Summary: "Microorganisms are ubiquitous and their contribution to human welfare is immense.Among the most important applications of microbial fermentation in maintenance of health is the production of antibiotics..."

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There are two ways in which a microbe may serve commercially. Either the cells are used as it is or the metabolite may get used it gets used up by the microbe or the metabolites can be harnessed and used. They are now the largest sources of secondary metabolites.

These metabolites serve important role in agriculture and human medicine. Fermentation under carefully controlled optimal conditions with specific strain of microbes result in production of commercial products such as amino acids, polysaccharides, growth hormones, food preservatives, vaccines, interferon etc. Antibiotic production is one of the most important application.

Just like any other metabolic end product, antibiotics are the result of series of metabolic reactions catalyzed by different enzymes. It is defined as any chemical compound of microbial origin which in dilute concentrations is able to effectively inhibit the growth of and / or destroy other microorganisms. Antimicrobial agents serve the same purpose but they need not be of microbial origin.

The term 'Antibiotic' was first coined by Waksman in 1942. The classification of antibiotics is primarily done on the basis of mechanism of action, biological spectrum, and chemical structure or by the source microbe. Evolution is fast making microbes resistant to the known antibiotics and hence there is a need for discovery and development of these classes of drugs.

Biological spectrum of action
Antibiotics are either Broad spectrum or narrow spectrum antibiotics. Broad spectrum antibiotics are effective against quite a number of bacterial species whereas the narrow spectrum antibiotics are effective against only a few bacterial species.

Source microbe
Generally antibiotics are named after the source microbe. For example streptomycin is isolated from Streptomyces species and actinomycin is the product of actinomycetes. Antibiotics are either bacterial or fungal origin.

Mechanism of action

Antibiotic effect is mainly due to five mechanisms of action.

a. Inhibition of cell wall synthesis - Penicillins, Cephalosporins, Vancomycin, Bacitracin.
b. Inhibition of protein synthesis - Chloramphenicol, Erythromycin, Tetracyclines, Streptomycin
c. Inhibition of DNA replication and transcription- Rifampin, Quinolones
d. Injuring plasma membrane - Polymyxin B
e. Inhibiting synthesis of essential metabolites - Trimethoprim, Sulfanilamide

Chemical structure

Antibiotics can be classified into any of the following groups based on their chemical structure.

Aminoglycosides are bactericidal in nature and as the name indicates has an aminocyclitol ring linked to aminosugars by glycosidic linkage. Spectinomycin is an exception which is bacteriostatic. Their activity is mainly attributed to the irreversible binding with the ribosomes causing mistranslation. Most are broad spectrum antibiotics. Anaerobic bacteria and rickettsia are not susceptible. Spectinomycin acts on the translation process by interacting with the formation of mRNA-ribosome complex during the process of protein synthesis.

Representative examples include Streptomycin, Gentamicin, Neomycin, Kanamycin, amikacin etc.

Macrolides are having a macrocyclic lactone in their chemical structure and belong to polyketides. The action is similar to aminoglycosides that they inhibit protein synthesis by binding with ribosomes. Most are bacteriostatic with a few being bactericidal at high concentrations.

Common macrolides include erythromycin, Azithromycin, Roxithromycin, Oleandomycin and Clarithromycin etc.

Penicillins are a group of antibiotics having the β-lactam ring in their structure. They inhibit the bacterial cell wall synthesis eventually killing the organism. The only disadvantage is their susceptibility to β-lactamase or Penicillinase enzyme which break open the β-lactam ring in Penicillin to form Penicilloic acid.

They are sometimes administered along with β-lactamase inhibitors to protect the penicillin. Peniciilinase resistant penicillins have been developed. Examples include Carbapenams, a broad spectrum antibiotic and Monobactam which is effective against Gram negative. Some of them cause severe hypersensitivity reactions.

Amoxicillin, Ampicillin, Oxacillin are some of the most commonly used among them.
Tetracyclines are another group of antibiotic containing polycyclic naphthone carboxide. They are broad spectrum bacteriostatic antibiotics inhibiting protein synthesis. The common antibiotics of the group are tetracycline, oxytetracycline, doxycycline and minocycline.

Chloramphenicol is a Nitrobenzene Derivative of dichloracetic acid. It is bacteriostatic and inhibits protein synthesis by binding to ribosomal subunit.

Fluoroquinolones are broad spectrum bactericidal antibiotics which interfere with the process of DNA replication by inhibiting bacterial DNA gyrase or topoisomerase II enzyme. The most common fluoroquinolones include ciprofloxacin, ofloxacin, norfloxacin etc.

Peptide antibiotics are Peptide linked D and L amino acids. There are two groups. The first group of peptde antibiotics are non ribosomal origin like the polymixins, bacitracins, glycopeptides etc. Apart from these, there are naturally occurring peptides which are produced by natural defense mechanisms in all species.

Those of the bacterial origin are mainly classified under bacteriocins which act on post transcriptional modification. There are some which inhibit peptidoglycan synthesis and others inhibit protein synthesis. Most of them are permeable to cell membranes.
Cephalosporins are bacteriocidal and inhibit the synthesis of the bacterial cell wall. They are further classified into four generation and each generation of antibiotics is more effective against gram negative bacteria than the previous one. The fourth generation is promising with broad spectrum of activity. Examples include cefepime and cefpirome
Polyens&nonpolyenes constitute the antifungal antibiotics. Ansamacrolides are (e.g. Streptovaricins and rifamycins) Naphto and benzoquinone nuclei derivatives. Anthracyclinc antibiotics like adriamycin&duanomycin has the Anthracycline ring in their structure.

Apart from these, there are antibiotics having other unique structures like cycloserine, novobiocin and fusidic acid.

Resistance to antibiotics is perhaps the most severe problem associated with the use of antibiotics and can be minimized by judicious use of antibiotics and developing more narrow- spectrum antibiotics which are more specific against the microbe.

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