Drug resistance of microorganisms // Drug Repurposing

Drug resistance of microorganisms

Researchers at the University of Michigan (UM) have obtained the first three-dimensional snapshots of the ‘assembly line’ within microorganisms that naturally produces antibiotics and other drugs. Their research has been published in two articles in the journal Nature.

Georgios Skiniotis, David Sherman, Janet Smith and Kristina Håkansson described the structure of a central enzyme in the assembly process that creates polyketides, a broad class of diverse and bioactive chemical compounds that comprises some of the most important antibiotics, antifungal agents, cancer chemotherapeutics and immunomodulators in wide clinical use.

“Ultimately, understanding the details of polyketide creation can allow us to successfully design and engineer systems for the production of novel products with high medicinal value, ” said Skiniotis, the corresponding author on both papers.

David Sherman, Georgios Skiniotis and Janet Smith in the cryo-EM suite in the Life Sciences Institute at the University of Michigan. Image credit: Erin Grimm, Life Sciences Institute.

Nearly two-thirds of all drugs currently used are derived partially or entirely from a natural source. But the natural process used by microorganisms to create the medicines has been a “black box”, said Smith, who added, “We knew something went in and something else came out, but we didn’t know what happened inside.”

“There were lots of models proposed and lots of debate and disagreement, but very little evidence, ” noted Sherman. “Over 15 years we were able to characterise the basic biochemical features of this remarkable biochemical assembly line, but high-resolution features remained beyond our grasp - until now.”

The polyketide synthase (PKS) enzyme was derived from a type of terrestrial bacteria called Streptomyces venezuelae, which produces pikromycin, an antibiotic precursor to the widely prescribed erythromycin. The researchers describe the enzymatic steps of the fifth cycle in a six-cycle biological assembly-line process that produces pikromycin. The structure was not what they had anticipated.

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Sickle cell

by coelentrate

Sickle cell is not the best example I gave. The best examples are lactose tolerance in humans and evolution of drug resistance in microbes because these are physical changes that humans have observed with their own eyes.
sickle cell is also circumstantial evidence. we think that the sickle cell allele should have dissapeared but it dsidn't. we guess it's malaria resistance. And we guess the reason is selective pressure.

Hard to say.

by pleni

Since bacteria don't fossilize, it is hard to determine what transitions have occurred. Here is a little bit of info on it. The interesting thing about bacteria is that one generation is very short compared to human generations. That is why we can see evolution happening in "real time" in bacteria, but can't see it in humans or other animals.
"Antibacterial resistance is an example of evolution in action. Whenever an antibiotic is used, there is always the chance that some of the bacteria will survive. Compared to the bacteria that were killed off, the survivors have genes that make them more resistant to the drug

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He noted that Lt. Cabral served as the Drug Awareness Resistance Education (DARE) officer for three years without being paid after the town went through a difficult financial time.