Predict mutations

With increase in incidence of antibacterial drug resistance it has now become   difficult to control even common infections like pneumonia or urinary tract infections with standard antibiotics.

Yes, there is an urgent need for new line of antimicrobials but so is the need for ways to maximize the effective lifespan of these drugs. Hence, there is research being conducted to predict superbugs’ response to new drugs.

In a recent advancement in the field of technology carried out by the researchers from Duke University , by using a software , a constantly-evolving infectious bacterium’s countermoves to one of these new drugs can be predicted ahead of time, before the drug is even tested on patients.

“This can help in anticipating the move of the opponent thereby making the chances of winning stronger than before.”

The research team has developed a computer algorithm that stands a good chance of beating a superbug at its own game. The software is called OSPREY and it can predict the mutations that bacteria can most likely undergo in response to a new drug before the drug before it is given to the patients.

The research findings are published in the journal Proceedings of the National Academy ofSciences, where the team describes how they tested OSPREY with the superbug MRSA (methicillin-resistant Staphylococcus aureus).

The researchers programmed the algorithm in such a way so that they could identify the genetic changes that MRSA would have to undergo in order to become resistant to a promising new class of experimental drug.

After they actually exposed MRSA to these experimental new drugs, they found some of the genetic changes the software had predicted did arose.

The study author Bruce Donald, a professor of computer science and biochemistry at Duke says that

“This gives us a window into the future to see what bacteria will do to evade drugs that we design before a drug is deployed.”

The team hopes the approach they are developing will give drug designers a head start in the race against superbugs, as co-author and Duke graduate student Pablo Gainza-Cirauqui explains:

“If we can somehow predict how bacteria might respond to a particular drug ahead of time, we can change the drug, or plan for the next one, or rule out therapies that are unlikely to remain effective for long.”

The software’s like OSPREY can definitely be advancement to the current method where scientists have to look up “libraries” of previously observed resistance mutations, an approach which is not necessarily satisfactory for predicting future mutations always according to the study team.

 Prof. Donald further explains that:

“With a new drug, there is always the possibility that the organism will develop different mutationsthat had never been seen before. This is what really worries physicians.”

“OSPREY – stands for Open Source Protein REdesign for You – is based on a protein design algorithm. It identifies changes to DNA sequences in the bacteria that would enable the resulting protein to block the drug while still being able to work normally.”

The team used a new class of drugs called propargyl-linked antifolates that attack a bacterial enzyme called dihydrofolatereductase (DHFR), used for building DNA and other tasks to be tested by OSPREY .These drugs are still to be tested in humans and might prove promising as a new treatment for MRSA infections.

Prof. Donald says,

The fact that we actually found the new predicted mutations in bacteria is very excitingWe might even be able to coax a pathogen into developing mutations that enable it to evade one drug, but that then make it particularly susceptible to a second drug, like a one-two punch.”

The team is now enhancing OSPREY to predict resistance mutations to drugs designed to treat E. coli and Enterococcusinfections.

They believe OSPREY can even prove to be a useful tool for predicting drug resistance in cancer, HIV, flu and other diseases where culturing resistant strains is harder than it is with bacteria.

About Ruchira Dhoke

A qualified medical microbiologist with an avidity to read enchant a deep passion for creating a good impacting masterpiece with my words .I am very fond of good old English literature and like listening to music and paint in my free time.

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