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New Ammunition to fight antibiotic resistant bacteria

By Costa Maragos Posted: February 24, 2016 6:00 a.m.

Members of the research team (l-r), Dr. Viktor Deineko, Dr. Hiroyuki Aoki, Dr. Sandra Zilles, Ashwani Kumar (PhD graduate student), Dr. Zoran Minic and Dr. Mohan Babu.
Members of the research team (l-r), Dr. Viktor Deineko, Dr. Hiroyuki Aoki, Dr. Sandra Zilles, Ashwani Kumar (PhD graduate student), Dr. Zoran Minic and Dr. Mohan Babu. Photo by Trevor Hopkin - U of R Photography.

There’s been a step forward in the battle against antibiotic-resistant bacteria and it’s thanks to a collaborative research project that involves the University of Regina.

The research team has mapped out the DNA damage pathways in Escherichia coli, normally referred to as E.coli.

The bacteria is commonly found in the intestines of humans and animals. E.coli pathogens cause mild discomfort for most people but they can also lead to serious complications including kidney failure, diarrhea, urinary tract infections and severe anemia.

Dr. Mohan Babu, assistant professor in the Department of Biochemistry, is senior author of the research project, which has been published in the peer-reviewed journal Cell Reports – a Cell Press Journal.

The impressive team includes researchers from The University of Toronto, The Hospital for Sick Kids in Toronto and the Harvard Medical School.

“Pathogens that cause disease in human bodies tend to have resistance to many existing antibiotics. It’s a big problem and that’s why clinical people are finding it difficult to cure infectious diseases,” says Babu who is also principle investigator of the Babu Lab located at the U of R’s Research and Innovation Centre.

“We looked at the kind of DNA repair of genes in bacterial systems that are being rewired,” says Babu. “We took 500 genes and mapped them against each other. That works out to around a quarter of a million interactions. These interactions were tested where bacteria normally grow in standard and DNA damage growth conditions.”

Figuring out that complex and tangled web of bacterial gene interactions is no small feat.

Sometimes, antibiotics will infiltrate a bacteria cell, like E.coli, and cause damage but not enough to destroy the cell. Think of an army that storms the barricades but stops there.

Given a second chance, bacteria tend to re-arm or re-wire themselves and potentially cause more damage. Finding out how the DNA of the ‘repaired’ bacteria functions could be the key to finding new pathways to fight them.

As noted in the research paper, “the genetic components of the bacterial DDR (DNA damaged response) have been studied extensively in isolation, how the underlying biological pathways interact functionally remains unclear.”

The research team has uncovered many DNA damaged pathways that appeared to be ‘re-wired’ when the bacteria was exposed to the genotoxin, an agent that can damage a cell, with the mutations potentially leading to cancer.
 
“If you examine broadly how cells are dealing with genotoxic stress, then appropriate drugs can be designed,” says Babu. “We feel our results will spur a deeper investigation into the molecular biology of these genome integrity pathways.”
 
Aside from Babu, the primary author of the research was conducted by the PhD graduate student Ashwani Kumar (co-supervised by Dr. Zilles from the department of Computer Science) and many other researchers from the Babu Lab.

Babu’s research was supported by grants from the Natural Sciences and Engineering Research Council’s Strategic Network Grant and Discovery Grant as well as Canadian Institutes of Health Research.  

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