Drugs for bacterial infections,how can i get rid of my urine infection last,how to get rid of brown skin discoloration - PDF 2016

10.08.2015, admin
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Abstract Puffer fish, Takifugu niphobles, collected from the Hong Kong coastal waters were screened for tetrodotoxin-producing bacteria. Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Vanderbilt chemists have discovered that the process bacteria undergo when they become drug resistant can act as a powerful tool for drug discovery. Their findings – reported this week in the Online Early Edition of the Proceedings of the National Academy of Sciences – should give a major boost to natural products drug discovery – the process of finding new drugs from compounds isolated from living organisms – by substantially increasing the number of novel compounds that scientists can extract from individual microorganisms.
Bacteria have traditionally been the source of important drugs such as antibiotics and anticancer agents. While investigating how bacteria develop drug resistance, Vanderbilt biochemists Brian Bachmann and John McLean discovered that strains of antibiotic-resistant bacteria express hundreds of compounds not produced by their progenitors, many of which are potential secondary metabolites.
The original purpose of the study was to take the most detailed look yet at what happens when microbes develop drug resistance. Working with Research Assistant Dagmara Derewacz and graduate students Cody Goodwin and Ruth McNees, Bachmann and McLean started with the well-characterized soil bacterium Nocardiopsis. The chemists then cultured the survivors (six streptomycin-resistant strains and five rifampicin-resistant strains) without the antibiotic and used McLean’s instrumental methods to profile the drug-like compounds that they produced. The structure of two of the drug-like molecules discovered by triggering Nocardius' drug-resistant response. McLean’s team has developed strategies that allow them to automatically identify and compare the relative uniqueness and the relative abundance of tens of thousands of molecules from which the hundreds of novel compounds were found.


In the antibiotic-resistant Nocardiopsis strains the researchers found a total of five compounds that were both unique enough and abundant enough to isolate, determine their molecular structures and test for biological activity. Brian Bachmann will be applying the results of this study to increase the productivity of the program to search for novel drugs produced by cave-dwelling microorganisms that he started several years ago. The most similar sequence obtained from bioinformatic search against the NCBInr database was the sequence from Raoultella terrigena (CCM3568, Accession no. The numbers represent the percentage of 1000 replications (bootstrap support) for which the same branching patterns were obtained. A Gram-negative, non-acid-fast, non-sporing and rod shaped bacterial strain (designated as gutB01) was isolated from the intestine of the puffer fish and was shown to produce tetrodotoxin (TTX).
Isolation and Identification of a New Tetrodotoxin-Producing Bacterial Species, Raoultella terrigena, from Hong Kong Marine Puffer Fish Takifugu niphobles . Researchers looking for new bacterially synthesized drugs have long known that bacterial genomes contain a large number of “silent genes” that contain the instructions for making drug-like compounds. We’ve known for a long time that there were large amounts of underground natural gas that we couldn’t extract using conventional methods but now we can, using hydraulic fracturing technology. Bachmann is an expert in natural products drug discovery and McLean, an assistant professor of chemistry, is a pioneer in the development of analytical instrumentation and chemical techniques that can identify thousands of different biological compounds simultaneously, such as ion mobility-mass spectrometry.
To complicate matters further, we are looking for new drug-like molecules, so by definition we are looking for something that has not been seen before,” said McLean. They exposed the bacterium to two different antibiotics – streptomycin and rifampicin – and observed the results.
The survivors had undergone extensive mutations, not only in the genes that produce secondary metabolites but also in the housekeeping genes that alter the way they make RNA and proteins.


Based on the same, the market has been segmented into fluoroquinolones, aminoglycosides, macrolides and others. But, until now, scientists have found it is very difficult to find ways to turn on the production of these compounds, known as secondary metabolites. In a similar fashion we think we can use bacteria’s antibiotic resistance to intensively mine the bacterial genome for new drug leads,” he said.
As a result, they determined that the resistant strains produced more than 300 compounds that were not expressed by the original organism.
Fluoroquinolones market for bacterial conjunctivitis has been further studied for ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, gatifloxacin and besifloxacin. The alignment of both sequences and their differences are shown (nucleotides highlighted with dotted lines).
NCBI accession numbers of the ITS sequences used for the study are EU623235 (Raoultella terrigena), EU623088 (Raoultella planticola), EU623097 (Raoultella ornithinolytica), DQ470481 (Raoultella sp.), EU623278 (Klebsiella pneumonia subsp. The TTX production ability of the strain was confirmed by mouse bioassay, ELISA and mass spectrometry (MALDI-TOF).
Our results reiterate that the TTX found in puffer fish was likely produced by the associated bacteria and TTX are widely produced amongst a diversity of bacterial species.



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