Prospects of managing few multi drug resistances world health organisation prioritized pathogens
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Abstract
Multidrug resistance (MDR) bacteria are considered as the most emerging problem in the
world. Various kinds of antibiotics are produced for treatment of those bacteria but being
resistance against them by various causes. The main cause is the misuse of the antibiotics by
consumers which enhance the bacteria to develop different resistance mechanisms such as:
lack of cell wall permeability, enzymatic deactivation of antibiotics, alters the target of
antibiotics as well as efflux mechanism and many more. Most of the antibiotics are
discovered by targeting the cell wall permeability and efflux pump. But antibiotics identified
are not effective to act as bactericidal and bacteriostatic which may be due to the lack of
knowledge related to the specific target of the bacteria.
Moreover, these kinds of antibiotics, have enhance in certain modification in the bacteria
causing mutations in genetic sites and converting them into extensive resistance bacteria
XDR) and multidrug resistance bacteria(MDR).Therefore, for specific identification of sites
as target and antibiotics for bacteria computational method should be used. This method is
being used as the most effective method to identify target molecule and to know
effectiveness of molecules against those bacteria without using lab equipment.
Some literature have reviewed that Streptomyces are being the most effective way to be
treated against different bacteria by developing different kinds of antibiotics. Antibiotics
produced were developed on the basis of targeting different sites of bacteria. Recently,
Streptomyces coelicolor is found be the most studied Streptomyces which is found to be
similar with Mycobacterium .So, instead of using BCG it is the most preferable one to act
against Mycobacterium tuberculosis without effecting human.
For the development of new drug ring structure is being preferable which can produce
biproduct from bacteria found in soil such as Streptomyces. In this study, target site was
identified by using the computation techniques such as the tools namely protein databank,
Discovery studio, pyrx etc. Target sites were taken as the protein TrmD, one of essential
proteins for bacteria for methylation process. S-Adenosyl methionine (SAM) or S-Adenosine
homocysteine (SAH) essential to carry out the activity of TrmD which was replaced by the
derivatives of indole such as: indole,indurubin,isatin etc and binding energy was calculated.
Higher binding energy indicates that it can replace original ligands and able to block the
methylation of the genetic material of bacteria. Furthermore, modified media was prepared
or the extraction of antibiotics in high concentration, and then AST was carried out. During
this process Candeula extract were used as comparative sample. Thus, it is presumed that
the ring structure phenolic compounds can potent for the antimicrobial activity and also act
as enhancer for other antibiotics producer bacteria.
