Friday, 9 January 2015

New Antibiotic Teixobactin Knocks Down Drug Resistant Bacteria


Antibiotic resistance has become the most insurmountable problem in recent years. The situation is particularly worse in India as antibiotics can be purchased over the counter without an authorised prescription. The issue is further aggravated due to the prevalent practice of personal medication. As a result even the most efficacious antibiotics are rendered incapable of fighting common hospital bound infections too. Disease resistant pathogens have become invincible. The fragile medical infrastructure in developing countries like India is unable to mitigate the burgeoning cases of antibiotic resistance.

According to Centre for Disease Control and Prevention nearly two million people are infected by bacteria, resistant to antibiotics and of those at least 23,000 people die. A new review on the antimicrobial review indicated that at the pace with which the resistant bacteria are multiplying, by 2050 it is estimated that 10 million people will die of otherwise curable diseases.  Several World leaders expressed anguish that antibiotic resistance might cause damage to a tune of $10 trillion for the global economy

Antibiotic resistance is a natural part of evolution. As humans discover new drugs to combat the infections, bacteria are acquiring resistance. Previously, by the time bacteria had evolved resistance man would have developed a new form of drug. Of late, due to human-influenced factors bacteria are acquiring resistance towards the existing drugs so quickly that Pharmacists are unable to create a new drug. As a result this crisis has turned out to be a man-made global threat and thousands of people are succumbing to diseases which are otherwise completely curable. To combat this problem most medical practitioners strictly warn against extensive usage of antibiotics.

In the latest break through scientists reported discovery of an antibiotic from an uncultivatable soil bacterium which shows no evidence of inducing the evolution of spontaneous resistance in its bacterial targets. The first set of the most successful antibiotics mined during early twentieth century are microbial natural products or their derivatives of soil bacteria and fungi. The golden age of antibiotics between 1940 and 1960 is marked by extensive use of these compounds for treating curable diseases.  Extensive mining of the soil bacteria resulted in obtaining compounds which are more or less chemically similar. Hence most of the antibiotics developed during that time had almost chemical configuration with minor variations. By 1980’s pharmaceutical companies turned their attention towards synthetic compounds which resulted in developing drugs for other diseases but failed to generate new set of antibiotics. Meanwhile, Actinomycetes, spore forming, soil bacteria has become favourite organism for antibiotic production as it is easily cultured in lab. Scientists have for long time ignored other rare taxa of soil bacteria which had unique chemical properties as they cannot be easily cultured. Due to the inability of culturing soil bacteria only 1% of them are studied so far for their antibiotic properties. Realising the grave folly, scientists developed new culturing techniques to cultivate rare taxa including insitu growth in natural environments.

Ling et al in their Nature paper which heralded the development of the new antibiotic, described a novel approach which revolutionised the culturing of soil bacteria which were difficult to grow in laboratory conditions. The new technique termed as iChip technology is a multichannel, miniature device used for high throughput production of rare cells directly in their source environment. Thus these species which replicate in the natural environment and fail to survive under the traditional lab methods are cultivated.

Using this technology the lab isolated 10,000 soil bacterial strains from which they prepared extracts and tested them for their ability to inhibit the growth of Staphylococcus aureus (a gram-positive bacterium that causes respiratory tract infections. The extracts of the bacterium that could kill the pathogenic bacterium are identified. The extract after the activity-guided purification is fractionated using several techniques and its antibiotic activity is again after every step. The new bacterium identified as Eleptheria terrae is the producer of the new generation antibiotic teixobactin.

Teixobactin basically inhibits cell wall synthesis by binding to the highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of teichoic acid). It is proved to be a potent chemical that can kill wide spectrum of disease-causing bacteria including Clostridium difficle (causes diarrhoea) and those which are resistant to vancomycin, pencillin and methicillin. The drug exhibited selective killing of bacteria even at very high doses and most importantly labs failed to generate Gram positive bacteria that is resistant to killing of teixobactin. Unfortunately, it is ineffective against gram negative bacteria which have developed a multi-drug resistance like Klebsiella pneumonia, pathogenic versions of E.coil, Neisseria gonorrhoeae, Pseudomonas aeruginosa.

Unlike the earlier antibiotics which targeted the bacterial enzymes involved in cell wall formation, teixobactin launches a double attack by blocking the building blocks of cell wall. Consequently the newly replicating bacteria will die. Hence bacteria evolving resistance against this drug would be unlikely or may be it might take several years. Human trials might begin two years from now. But for now teixobactin seems to offer a great promise against the Gram positive bacteria.
 
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