Meducator: McMaster researchers adopts a different strategy to combat antibiotic resistance

Avrilynn Ding
The Meducator

Although antibiotic resistance has been identified as a problem since the first introduction of penicillin, it has recently emerged as a serious public health concern.

Currently, one in 12 adults in Canadian hospitals are infected with bacterial microbes that are immune to most or all available sildenafil antibiotics. A report released by the Ontario Medical Association in March recommended governments to establish regulations to combat antibiotics overuse in medicine and agriculture. Ironically, while antibiotic resistance is a growing threat, the pharmaceutical industry largely abandoned antibiotics development in favour of researching treatments for other diseases. The majority of antibiotics used today were discovered before 1960, and target limited pathways in bacteria.

To address the issue, researchers at McMaster University recently developed a novel approach to screening for new antibiotics. Dr. Eric Brown, a professor in the Department of Biochemistry and Biomedical Sciences, led the study, published in Nature Chemical Biology. Rather than searching for antibiotics under conventional nutrient-rich conditions in the laboratory, researchers targeted bacteria growth under nutrient-limited conditions that closer resemble conditions in the human body that bacteria face during infections.

“Convention says you try to kill bacteria under the richest growth condition that you can create in the laboratory,” Brown said.

“And yet we know that life is not that kind to bacteria when they are infecting the human body. They actually struggle quite a bit.”

The study focused on antibiotics against Escherichia coli, a common bacterium used in research. The researchers used a medium containing four salts, supplemented by 0.4% glucose and 20mM ammonium chloride, to create a growth environment lacking the vitamins and amino acids the bacteria require. They then screened for antibacterial compounds by shifting through a library of 30,000 synthetic molecules and testing for chemicals that can block E. coli’s ability to synthesize its own essential nutrients.

Using the method, the research team discovered and characterized three new antibacterial compounds, designated as MAC168425, MAC173979 and MAC13772. Each chemical acts on a different pathway in E. coli to disrupt its ability to create or use a particular nutrient. MAC168425 interferes with the metabolism of glycine, a major amino acid used to build many proteins. MAC173979 prevents E. coli from making vitamin B9 by decreasing the biosynthesis of an intermediary molecule, while MAC173979 prevents the biosynthesis of vitamin B7 by inhibiting a key enzyme. In addition to the three molecules, researchers also identified 68 other chemicals that showed active antibiotic properties in nutrient-limited medium.

Brown’s findings have great implications in pharmaceutics by demonstrating the possibility and feasibility of a new method for antibiotic development. Not only does it suggest an alternative process for identifying antibiotic chemicals, it also opens research to a new class of antibiotics that target the nutrient synthesis mechanisms of bacteria. Although further research is required to transform the three antibiotic compounds into antibiotics, the study’s approach to discovering antibiotic chemicals has great potential to address antibiotic resistance.