Biologists have found used to characterize new antibiotics can screen natural products quickly for compounds capable of controlling antibiotic resistant bacteria. Antibiotic resistance is increasing at an alarming rate. The Review on Antimicrobial Resistance, a publication established to produce an analysis of the global problems of antimicrobial resistance, recently predicted that by 2050, the worldwide toll from drug resistant bacterial infections could reach 10 million deaths per year, more than cancer (8.2 million) and diabetes (1.5 million) combined.
America currently leads the world in drug research but the regulatory costs of approval, coupled with unlimited lawsuit judgments for anyone who is harmed, have made drug discovery so expensive that few companies want to research new antibiotics; politicians like Senator Bernie Sanders, who are solidly anti-science, routinely claim they will put a cap on costs for drugs, so the $150,000 per year drug that recently helped Jimmy Carter with cancer, or the $80,000 per year Hepatitis C cure, would never get made, and that means that antibiotics which everyone wants cheap are not worth pursuing.
But perhaps costs can be saved in the early stages.
One of the main problems in identifying new antibiotics and bringing them to market is a lack of understanding how the molecules work.
A new technique could permit chemists and others to understand how mixtures of potential antibiotics from microorganisms work without first purifying them. Most of the world's clinically useful antibiotics are derived from molecules referred to as natural products because they are naturally produced by microorganisms. This includes penicillin and streptomycin, the first two antibiotics widely used clinically beginning in the 1940's. As pathogens evolved resistance to penicillin and streptomycin, new natural product antibiotics were needed.
During the 1950's and 1960's, a large number of antibiotics were discovered. But after 75 years of intensively screening microbes for antibiotics, scientists appear to have harvested all of the easy to find antibiotics. Attempts to find antibiotics from natural products now often result on the repeated isolation of one of the hundreds of molecules that have been already discovered.
Traditional approaches for isolating natural product antibiotics require molecules that have killing activity to be purified before performing extensive experiments to determine how they work.
"This is a very slow, labor intensive process that typically requires many months of effort, and frequently ends with discovering that the molecule does not have a new or interesting mechanism of action," said Joe Pogliano, a professor of biology at UC San Diego and a co-author on the study. "Our method solves this problem by providing a new way to find a unique needle in a haystack of needles. Before any of the time-intensive work has been started, we can determine which samples have an activity that is new or interesting."
"It's easy to identify microbes that produce antibiotics that kill bacteria. The difficult part is determining which microbes produce a new molecule with a new activity. With our new method, we can determine which strain is producing an interesting activity and then follow that specific activity during purification to make sure we purify the right molecule. This new approach will help to open up the discovery pipeline, allowing more potential antibiotic producing strains to be rapidly screened for antibiotics that are active against multidrug resistant bacterial pathogens.
"Our initial discovery allowed us to perform the equivalent of an autopsy on bacterial cells and is changing the way industry searches for new antibiotics from collections of pure chemicals," said Pogliano. "But we didn't know if it would work for identifying antibiotics found in natural product extracts, which are very complex mixtures frequently filled with multiple types of antibiotics."
This technology is being commercialized by Linnaeus Bioscience Inc.
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