Tuesday, December 16, 2014

Exploring aquatic sources in search of future antibiotics-Fight against drug resistance in bacteria

Man cohabits with billions of other living creatures, tiny, small or big numbering trillions and trillions. Some of them are visible to the naked eyes while extremely small microorganisms cannot be seen with out the help of powerful microscopes. The living environment is full of viruses, bacteria and fungi, most of them being benign and pose not much hazard to human life. But a small fraction of them can cause infection in human body which if not treated with antibacterial or bacteriostatic drugs can be very harmful and in many cases become fatal. Antibiotics, several in number, discovered in nineteen twenty eight starting with Penicillin, are the front line of defence against pathogenic microorganisms. However over use  and misuse of these antibiotics during the lat 6 decades have created an unenviable situation where many pathogens are developing resistance against the killing power of these wonder chemicals. Why?

The major culprits are indifferent physicians who prescribe antibiotics at the "drop of a hat" to most patients coming to them whether actually needed or not and the animal feed industry which incorporates these antibiotics in small amounts in their products for better growth of cattle and poultry birds. Constant exposure through the meat products carrying the antibiotic residues and over exposure through physicians' frequent prescription created opportunities to microorganisms to evolve mechanisms to overcome the lethal effect of antibiotic drugs over a period of time. Imagine how insensitive the animal food industry in a country like America could be considering that more than 80% of available antibiotics are used by the feed industry in that country during the last few years. This malpractice is spreading to other countries also thus expanding the dangers posed by antibiotic resistant super bugs in creating havoc with human lives. How to deal with this precarious and fast emerging situation that can be a threat to humanity?

Pharmaceutical industry is lagging behind in developing newer generation antibiotics, possibly because of the huge investments required to see through the process of testing and safety clearance while government led research investments are practically non-existent. We owe to many Universities and academic institutions for the scientific strides made by scientists and scholars in discovering new approaches in dealing with air-borne, water-borne and food-borne diseases working in different parts of the world.  One such area is discovery of Antimicrobial Peptides ( AMP) which were shown to have bactericidal, virucidal and fungicidal properties that can compliment the strength of current biotics and counter act the ability of pathogens to develop resistance. AMPs are short chain peptides containing 12-50 amino acids and mostly contain 2 or more positively charged residues provided by arginine, lysine and histidine. Besides they also contain hydrophobic residues to the extent of more than 50% of the chain length.They are derived from a variety of sources including humans, insects, amphibians, fish, pigs, cattle, crabs, fruit flies etc. But how feasible it is to manufacture them economically and logistically?

From whatever is known about these unique biological molecules, it is clear that scientifically they can counter act many micro vectors efficiently without causing any resistance in the invading species. Initial contact between the host surface and the vector takes place electrostatically as bacterial surfaces are anionic in nature. AMPs target the cytoplasmic membrane besides interfering with DNA synthesis, proteins synthesis and folding and cell wall synthesis resulting in a catastrophe leading to their death. One major limitation could be presence of cholesterol in human cells which makes them less reactive with invading vectors. However ribosomally synthesised peptides, unlike their non-ribosomally made ones are least prone to create drug resistance. Examples are Gramicidin, Bacitracin, Polymyxin and Vancomycin which are increasingly becoming popular as antibiotic alternatives. How can these peptide molecules be made commercially available? 

AMPs are present in almost all higher forms of living creatures in the dermis and they form the first line of defence against invaders when infection takes place. That is why they can be extracted from almost all of them including humans. However from a practical view point for a sustained supply of any product of uniform quality a reliable source needs to be identified. Recent works by a few scientific groups have identified aquatic creatures as a good source from which highly efficient AMPs can be made in a sustainable way. Gills in most fish species have AMPs that give protection to them against water borne infections while water is filtered through these gills for breathing. Each fish species secretes AMPs with different structural features offering a vast range for selection regarding their effectiveness against different species. Some of the fish species from which AMPs have be recovered and studies include Rainbow Trout, Carp, Winter Flounder, American Halibut, Atlantic Salmon, Zebra Fish, Puffer Fish, Tilapia and a few others. Diversity of genomic sequence encoding fish AMPs has been extensively studied and they can be a sustainable source for synthetic recombinant AMP products for use by therapeutic industry eventually. 

Recently progress has been made in bonding fish derived AMPs to Silicone, Gold and Silver surfaces so that the latter can be used in designing highly effective therapeutic applications in human beings. In transplantation and organ repair surgeries such coated surfaces can preempt contamination. and post surgical complications. Heart valve replacements or stent implants can also have such coatings for which further application studies are called for. As for direct use in human beings in place of current antibiotics, delivery mode has to be worked out for the AMPs to attack the invading organisms at the affected cites. Exciting developments in fish AMPs can be expected in the coming years and there is hope that the current antibiotic resistance among pathogens can be dealt with through fish AMPs.


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