Antibiotics are commonly used around the world to cure diseases caused by bacteria. But as the World Health Organization and other international bodies have pointed out, the global increase of antibiotic resistance is a rapidly worsening problem. And since antibiotics are also an essential part of modern medicine, as prophylactic treatment during surgeries and cancer therapy, rising resistance of bacteria presents even more of a danger.
That’s why researchers are busy devising strategies to address this threat to human health – and Université de Montréal is at the forefront of the fight.
One of the ways antibiotic resistance genes spread in hospitals and in the environment is that the genes are coded on plasmids that transfer between bacteria. A plasmid is a DNA fragment found in bacteria or yeasts. It carries genes useful for bacteria, especially when these genes encode proteins that can make bacteria resistant to antibiotics.Now a team of scientists at UdeM’s Department of Biochemistry and Molecular Medicine has come up with a novel approach to block the transfer of resistance genes. The study by Bastien Casu, Tarun Arya, Benoit Bessette and Christian Baron was published in early November in Scientific Reports.
A library of molecules
The researchers screened a library of small chemical molecules for those that bind to the TraE protein, an essential component of the plasmid transfer machinery. Analysis by X-ray crystallography revealed the exact binding site of these molecules on TraE. Having precise information on the binding site enabled the researchers to design more potent binding molecules that, in the end, reduced the transfer of antibiotic-resistant, gene-carrying plasmids.
Baron hopes the strategy can be used to discover more inhibitors of the transfer of resistant genes.
“You want to be able to find the ‘soft spot’ on a protein, and target it and poke it so that the protein cannot function,” said Baron, the Faculty of Medicine’s vice-dean of research and development. “Other plasmids have similar proteins, some have different proteins, but I think the value of our study on TraE is that by knowing the molecular structure of these proteins we can devise methods to inhibit their function.”
Working with IRIC
Building on their encouraging new data, Baron and his colleagues are now working with the medicinal chemists at UdeM’s IRIC (Institut de recherche en immunologie et cancérologie) to develop the new molecules into powerful inhibitors of antibiotic resistance gene transfer. Such molecules could one day be applied in clinics in hospitals that are hotbeds of resistance, Baron hopes.
Ultimately, reducing the transfer of antibiotic-resistance plasmids could help preserve the potency of antibiotics, contributing to an overall strategy to help improve human health, he added.
“The beauty of what we are working on here is that the proteins are very similar to proteins that bacteria use to cause disease. So from what we learned about the TraE protein and about finding its ‘soft spot,’ we can actually apply this approach to other bacteria that cause diseases. One of those is Helicobacter pylori, which is a gastric pathogen that causes ulcers and stomach cancers. We’re working on that one specifically now, but there are many others.”
Four years of work
It took the UdeM team four years to arrive at the findings being published now – enough time for antibiotic resistance to grow into an ever-more worrisome global problem.
UdeM pediatric physician Joanne Liu, the international president of Doctors Without Borders, has called it “a tsunami,” and Baron believes she’s not exaggerating. “It’s a very good image to use, because we all know it’s coming. It’s not like a splash in your face every single day, but we all see the tide is rising.
“They say that by 2050, 50 million people will die from antibiotic resistant infections,” said the Toronto-born, German-raised researcher. “The day when we can’t treat infections with antibiotics is coming. Nevertheless, people should have hope. Science will bring new ideas and new solutions to this problem. There’s a big mobilization now going on in the world on this issue. I wouldn’t say I feel safe, but it’s clear we’re making progress.”
The Latest on: Antibiotic resistance
FDA Grants QIDP Designation to Acurx's Lead Antibiotic Product Candidate, ACX-362E for Clostridium Difficile Infection
on June 20, 2018 at 11:50 am
detect and diagnose antibiotic-resistant infections. Qualifying pathogens are defined by the GAIN Act to include multi-drug resistant Gram-negative bacteria, including Pseudomonas, Acinetobacter, Klebsiella, and Escherichia coli species; resistant Gram ... […]
European Parliament restricts antibiotic use in food-producing livestock
on June 20, 2018 at 11:00 am
n the latest bid to thwart antibiotic resistance, a European Parliament committee unanimously voted to adopt a deal with the European Council to limit the medicines in food-producing livestock. Under the new rules, ordinary antibiotic use for preventing ... […]
Sharing Your Illness On Social Media Helps Fight Antibiotic Resistance
on June 20, 2018 at 10:26 am
You can be sure the information you share could one day offer you the chance to avoid other infection troubles in the future. When we're sick, we tend to share our misery with others. For most of human history, we've been limited to family, friends, health ... […]
How Is Toothpaste Accelerating Antibiotic Resistance?
on June 20, 2018 at 7:33 am
An ingredient commonly found in toothpaste could be exacerbating the global problem of antibiotic resistance, according to researchers from the University of Queensland (UQ), Australia. The substance in question, triclosan, which is used in thousands of ... […]
Fragile Antibiotic Supply Chains Are Leading to Frequent Shortages, Worsening Antimicrobial Resistance
on June 20, 2018 at 4:00 am
Antibiotic supply chains are fragile and at risk of collapsing, warns a new white paper from the Amsterdam-based Access to Medicine Foundation. Shortages of specific antibiotics are causing price hikes, delayed treatment and the prescription of lower ... […]
Deep-sea marine sponges may hold key to antibiotic drug resistance
on June 19, 2018 at 1:51 pm
FAU's Harbor Branch houses more than 1,000 strains of actinobacteria, one of the most prolific microbial groups for the production of natural products. Derived from sea sponges and other macro-organisms, several strains were identified for their potent ... […]
Toothpaste and hand wash are causing antibiotic resistance
on June 19, 2018 at 11:29 am
A common ingredient in toothpaste and hand wash could be contributing to antibiotic resistance, according to new research. The study focused on triclosan, a compound used in more than 2000 personal care products. A study led by Dr Jianhua Guo from UQ's ... […]
Pizza Hut commits to antibiotic-free chicken wings by 2022
on June 19, 2018 at 5:42 am
Even so, in removing the ones that matter to current human medicine, fast-food restaurants are helping to ameliorate the problem of antibiotic resistance, which the regular consumption of chicken pumped full of antibiotics has created. It’s encouraging ... […]
Big data targets drug resistance
on June 15, 2018 at 2:02 pm
Maha Farhat, assistant professor of biomedical informatics and one of the organizers of a symposium on the topic, said antibiotic resistance has reached “epidemic proportions” but, with more data available than ever, there’s hope that medical science ... […]
A warmer planet might make deadly bacteria more resistant to antibiotics
on June 14, 2018 at 1:00 pm
Tom Patterson became ill in 2015 while vacationing in Egypt. He was felled by Acinetobacter baumannii, an often deadly bacterium resistant to every antibiotic his doctors tried. Patterson, a University of California San Diego psychiatry professor, should ... […]
via Google News and Bing News