Discovery could lead to stronger antibiotics

Montreal, QC – Researchers at McGill University have made a fundamental breakthrough that could pave the way to a better class of drugs to combat the growing problem of antibiotic resistance.

By mapping the first known three-dimensional structure of a protein complex involved in bacterial iron uptake, the team has made significant strides in the understanding of a process vital to the survival of bacteria. Long considered among the world’s most pressing public health concerns in hospitals and clinics, drug-resistant infections have resulted in deadly outbreaks of diseases such as meningitis and pneumonia.

James Coulton, a professor in the Faculty of Medicine, department of microbiology and immunology, and Peter Pawelek, research associate, and their team authored the study, “Structure of TonB in Complex with FhuA, E.coli Outer-Membrane Receptor,” was published in the June 2 edition of the weekly magazine Science. The research received funds from the Canadian Institutes for Health Research, Canada Foundation for Innovation and the Natural Sciences and Engineering Research Council.

Due to widespread and improper use of antibiotics, many bacteria have developed ways to circumvent their effects. In collaboration with Marc Allaire at Brookhaven National Laboratory in Upton, New York, the McGill team produced a model that reveals the nature of the interactions between the iron receptor FhuA and its partner protein TonB as they occur in an E.coli bacterial cell. “Picture TonB as a hand, gripping the handle of the FhuA receptor,” explained Pawelek. “When the iron-containing nutrient is bound in the barrel of the receptor, TonB uses energy from the cell to pull on the handle to release a ‘trap door’ that allows the nutrient to pass through the barrel and into the cell.”

Identifying the processes by which bacteria access essential nutrients such as iron can provide researchers with new antibacterial targets, thereby facilitating the development of a new class of drugs that can kill infectious bacteria by starving them in the host.