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Research

Researchers discover new toxin that impedes bacterial growth

This article was first published on Brighter World. Read the original article.

An international research collaboration has discovered a new bacteria-killing toxin that shows promise of impacting superbug infectious diseases.

The discovery of this growth-inhibiting toxin, which bacteria inject into rival bacteria to gain a competitive advantage, was published today in the journal Nature.

The discovery is the result of teamwork by co-senior authors John Whitney, assistant professor of the Department of Biochemistry and Biomedical Sciences at McMaster University, and Mike Laub, professor of biology at the Massachusetts Institute of Technology (MIT).

Whitney and his PhD student Shehryar Ahmad at McMaster’s Michael G. DeGroote Institute for Infectious Disease Research were studying how bacteria secrete antibacterial molecules when they came across a new toxin. This toxin was an antibacterial enzyme, one the researchers had never seen before.

After determining the molecular structure of this toxin, Whitney and Ahmad realized that it resembles enzymes that synthesize a well-known bacterial signalling molecule called (p)ppGpp. This molecule normally helps bacteria survive under stressful conditions, such as exposure to antibiotics.

“The 3D structure of this toxin was at first puzzling because no known toxins look like enzymes that make (p)ppGpp, and (p)ppGpp itself is not a toxin,” said Ahmad.

Suspecting the toxin might kill bacteria by overproducing harmful quantities of (p)ppGpp, the McMaster team shared their findings with Laub, an investigator of the U.S. Howard Hughes Medical Institute.

Boyuan Wang, a postdoctoral researcher in the Laub lab who specializes in (p)ppGpp signaling, examined the activity of the newly discovered enzyme. He soon realized that rather than making (p)ppGpp, this enzyme instead produced a poorly understood but related molecule called (p)ppApp. Somehow, the production of (p)ppApp was harmful to bacteria.

The researchers determined that the rapid production of (p)ppApp by this enzyme toxin depletes cells of a molecule called ATP. ATP is often referred to as the ‘energy currency of the cell’ so when the supply of ATP is exhausted, essential cellular processes are compromised and the bacteria die.

“I find it absolutely fascinating that evolution has essentially “repurposed” an enzyme that normally helps bacteria survive antibiotic treatment and, instead, has deployed it for use as an antibacterial weapon,” said Whitney.

The research conducted at McMaster University was funded by the Canadian Institutes for Health Research and is affiliated with the CIHR Institute for Infection and Immunity (CIHR-III) hosted at McMaster University with additional funding from the David Braley Centre for Antibiotic Discovery. The research at MIT was supported by the Howard Hughes Medical Institute and the U.S. National Institutes of Health.

“This is an important discovery with potential implications for developing alternatives to antibiotics, a global priority in the fight against antimicrobial resistance. It is heartening to see that young Canadian researchers like Dr. Whitney are thriving and emerging as leaders in this area,” said Charu Kaushic, scientific director of the CIHR-III and a professor of pathology and molecular medicine at McMaster.

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Research

eHealth against antimicrobial resistance

This article was first published on Brighter World. Read the original article.

A forward-looking McMaster donor is investing $7 million in a new research centre dedicated specifically to tackle the growing global threat of antimicrobial resistance.

David Braley, whose gifts to the university include a $50-million investment in McMaster teaching, learning and health-care research and delivery, has allocated $7 million from that 2007 gift towards the new David Braley Centre for Antibiotic Discovery.

The centre will operate from the Michael G. DeGroote Institute for Infectious Disease Research, whose labs and offices are located on campus in the Michael G. DeGroote Centre for Learning and Discovery.

Researchers associated with the new David Braley Centre for Antibiotic Discovery. Photo by Georgia Kirkos.

“This is a very timely investment,” says Paul O’Byrne, dean and vice- president, Faculty of Health Sciences. “This provides fresh resources to a team of researchers who are among the world’s leaders in their field. Creating this centre gives them the chance to do their best work at a time in history when it’s needed most.”

The funding comes from a portion of Braley’s 2007 gift that had been designated for emerging health-care research priorities.

The David Braley Centre for Antibiotic Discovery will be home to McMaster’s leading researchers in the field of antimicrobial resistance, or AMR. The new resources will allow the team to concentrate more specific effort on that problem.

“Antimicrobial resistance is a slow-moving catastrophe, but make no mistake: within the next 30 years, it will kill millions, strangle our health-care systems and significantly alter life as we know it unless we develop new ways to attack the problem,” says Gerry Wright, who heads both the David Braley Centre for Antibiotic Discovery and the Institute for Infectious Disease Research.  “The opportunity to open this centre is a hopeful sign, and we are grateful for Mr. Braley’s vision and his vote of confidence. This problem must be solved, and it can be solved.”

Dr. Gerry Wright standing at a podium in a hallway in front of a black curtain at the opening of the David Braley Centre for Antibiotic Discovery
Gerry Wright, director of the Institute for Infectious Disease Research and the new David Braley Centre for Antibiotic Discovery, addresses the crowd at the opening of the new research centre. Photo by Georgia Kirkos.

The waning effectiveness of traditional antibiotics gives urgency to the search for new forms of antibiotics and other ways to boost the effectiveness of existing drugs.

Widespread use of antibiotics in agriculture and medicine has accelerated resistance to penicillin and its related medicines, as bacteria evolve to meet the threat.

Infection control and treatment without antibiotics could cast the world back to the early 1900s, when infectious diseases routinely killed people, Wright says.

Today, at least 700,000 people around the world – including 2,000 in Canada ­­– die each year as a result of drug-resistant diseases. The global total is expected to rise to 10 million deaths per year by 2050 if no new solutions are found.

The medical costs associated with AMR are predicted to reach $100 trillion within that same time frame.

Close-up of a lab coat that reads
Photo by Georgia Kirkos.

This year, the United Nations published a report projecting that without immediate global action, AMR could force up to 24 million people into extreme poverty by the year 2030.