NEW APPROACH IN FIGHTING BACTERIAL PATHOGENS-

Modern antibiotic treatment for various diseases started after the discovery of Penicillin in 1928 and man has been discovering more and more antibiotics with increasing potency. However the golden age of antibiotics seems to be fading fast with the disease vectors developing capability to withstand the lethal action of most antibiotics presently available in the arsenal. The pharmaceutical industry is slowing down its research to come out with new antibiotics because of the astronomical cost involved for such efforts and the increasingly rigid standards for safety establishment by the regulatory authorities world over. It is against such a bleak canvas that the new discovery reported from the US by a group of research scientists which claims that some chemicals can disrupt the protein synthesis in the invading cells of pathogens disabling their ability to replicate. This molecular approach involving screening of thousands of chemical molecules is tedious and time consuming. Years of research seems to have been rewarded with a single chemical identified by them capable of tackling virulent E.coli, Shigella bacteria, Mycobacterium and Anthrax  without harming the host body. Here is a take on this exciting development.

To discover which small molecules might be capable of disrupting trans-translation, the team began with a process called high-throughput screening -- a method of trying out many thousands of small molecules with the hope of discovering one or more that might be effective at combating certain pathogens. "Our team tested about 663,000 different molecules against a strain of E. coli bacteria and monitored how they were affecting its trans-translation process," Keiler said. At the end of this phase of testing, Keiler and his team had found 46 different molecules that appeared to be effective in disrupting the trans-translation process. The next step was to test these molecules' performance in another genus of bacteria (Shigella) that is known to cause food poisoning. This genus is related to Salmonella and to the organism that causes anthrax (Bacillus anthracis), which sometimes can be lethal in humans and other animals. "Of the 46 molecules that were shown to affect trans-translation, one called KKL-35 jumped out as the most promising," Keiler said. "We found that the KKL-35 molecule inhibits the growth of very distantly related bacteria, and this suggests that it may have antibiotic activity against a very broad spectrum of species." As for the Shigella and Bacillus anthracis bacteria, Keiler said his team was able to show that, "in the presence of the KKL-35 molecule, these cells died specifically because the molecule halted the trans-translation process." Keiler's team also found that, compared with currently used tuberculosis drug therapies, the KKL-35 molecule was 100-times more effective at inhibiting the growth of the strain of bacteria that causes tuberculosis (Mycobacterium tuberculosis). Keiler added that one of the most exciting features of an antibiotic designed from the KKL-35 molecule is that drug resistance is not very likely to develop in mutant strains of the targeted bacteria. "In our laboratory experiments, we found no mutant strains that were resistant to KKL-35," Keiler said. "Resistant mutants probably could evolve eventually, but at least it looks like it will be very difficult. That means resistant mutants might be slow to arise and spread."

It is understandable that the successful scientists did not want to reveal the identity of the chemical as the expenditure for development might have to be recouped by patenting the discovery. What is significant is that this work has opened a new line of investigation that has potential to discover many more molecules with antibacterial potency. The claim that use of chemicals at molecular level does not allow the bacteria to develop resistance in the short term, though continuous use for years will only reveal whether such resistance is really not possible in this case. Of course the new development will take several years before becoming part of a standard treatment regime.  

V.H.POTTY
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