Friday, April 1, 2016

New Generation Antimicrobial Drugs for Treating Human Diseases

More than one hundred years ago Paul Ehrlich, postulated creating “magic bullets” for using chemotherapeutic agents to fight against human diseases. During those years, maximum number of human deaths was due to microbial diseases. Different kinds of synthetic drugs were discovered and used over the years, the last ones being the “sulfonamides” before the ground breaking discovery of penicillin was made by Alexander Fleming in 1928. The era of “antibiotics” continued for a long time and is going strong up to the present time even though antibiotic resistant microorganisms are fast developing. The methicillin-resistant Staphylococcus aureus has created fear in the hospital-setting causing diseases to the patients, which in many cases become fatal. The development of multi-drug resistant tuberculosis strains is another example which creates significant worries among poor nations.

The present day medical research has moved from treating microbial diseases to treating human diseases emanating from systemic bodily defects such as diabetes, arthritis, cardiovascular diseases, kidney and liver diseases, nerve related diseases such as Alzheimer’s and Parkinson’s diseases, cancer and several others. To treat all these conditions mainly the aim has been to develop technologies to produce substances that body produces for its harmony such as proteins of diverse kinds including insulin, cytokines and various other enzymes. The aim was to treat patients with “replacement therapy”, providing the materials that body requires but cannot produce within the body because of defects. The other approach was to scientifically understand the concept of “ligand-receptor interaction” with reference to bodily macrolides such as proteins, nucleic acids, carbohydrates, peptidoglycans etc. and to treat most such conditions by attempting to modulate cellular communication and inter-cellular modification of substances and also to reduce cellular inflammation. In doing so, several recombinant proteins and monoclonal antibodies started getting evolved and entering into the treatment regimen of human medical armory. At the moment more than 150 such products are in use globally. Another approach to treat bodily afflictions has been to “regenerate” the defective tissues by utilizing “stem cells” with the idea that the defective tissues would be “repaired”. This approach continues today at various laboratories and several new methods and technologies are anticipated to emerge. The present approach is mainly “autologous” in nature.

In the meantime, the disease producing microbes that were contained by use of “antibiotics” have become stronger and resistant to the known antibiotics to humankind. Resistant microbes have emerged in their intense desire to survive in environments “soaked” in antibiotics. Interestingly, the natural antibiotic molecules were isolated from some microbial sources. Even though many such natural antibiotics had been “modified” by human intervention, the essential chemical structure of those molecules was learnt by human kind by studying the natural molecules. The survival instinct by which the bacteria had evolved themselves to survive in an environment surrounded by “enemy bacteria” was “stolen” and modified by the “enemy bacteria” and thus the “enemy bacteria” recreated themselves as the resistant species. Development of antibiotic resistance in nature is therefore essentially a phenomenon of “self-readjustment” and “self-recreation” with an intense desire to survive. This natural law was understood by human kind from early 70s and efforts continued to develop more powerful antibiotics. However, this approach would be abandoned in course of time and newer methods are to be evolved. In the light of such thinking, it was discovered that a large number of viruses exist in nature that can “kill” the bacteria. The natural reserve of such a pool was enormous. It was further observed that the huge pool of viruses were continuously growing into their host-microbe and were bursting open their hosts from within. This was done by producing specific kinds of enzymes by the viruses that were capable of tearing off the peptidoglycan cell walls of the bacteria. This is a natural phenomenon. Once this concept was understood, several scientists started to investigate if such proteins could be produced in large quantities to contain the target bacteria. On pursuing this concept, recently a drug has been discovered which is known by the name CF-301 and is an enzyme that kills  Staphylococcus aureus in mouse model. The drug was discovered by M/s ContraFect Corporation, USA. It is anticipated that many such drugs would be discovered using the approach of identifying enzymes that can “dissolve” the peptideoglycan cell wall of bacteria from within. Once such enzymes are discovered and structures identified, these would certainly be produced in large quantities in fermentors using approprie genetically modified microbes such as E.coli and yeast and would be used to contain the “resistant bacteria”. The enzymes would “dissolve” the peptidoglycan cell wall of the bacteria and would kill. However, such discovery approaches would not be easy. Very sophisticated laboratories with highly talented scientists would have to work in R&D institutions to undertake basic and applied research to come up with new products for mankind. Only then the era of antibiotics will come to a close.

1 comment:

  1. Dear Sir,
    Thanks for sharing such a wonderful summarize infromation about ongoing acitivites in antimicrobial drug discovery, Effect, cause and future.