University of Guelph microbiologist discovers a revolutionary technique in treating disease
In the effort to preserve health, medical doctors, engineers, pharmacists, and biologists battle against rapidly evolving pathogens. One such target is pathogenic bacteria. Bacteria are extremely versatile organisms; varying in shape, inhabited environment and function. Most bacteria are harmless to humans, and many can be beneficial and even essential, to human health.
It doesn’t take more than a case of food poisoning, however, to remember the dangers some of these microorganisms can cause. Escherichia coli (E. coli), Neisseria meningitides (the bacteria responsible for meningitis), and Haemophilus influenza (the cause for influenza pandemics). These are some of the more dangerous species that captured the attention of Lisa Willis, a PhD student in the Department of Molecular and Cellular Biology (MCB). With her supervisor, University of Guelph professor Chris Whitfield, plus a team of researchers from the National Research Council of Canada and the University of Alberta, Willis has discovered an important tool for the future of medicine.
A common classification of bacteria is the division between Gram-positive and Gram-negative. The difference between the two bacterium is in their external structure. Gram-positive bacteria have an exoskeleton of peptidoglycan (polymer of sugars and amino acids) coating the internal cell membrane. Gram-negative bacteria possess additional physical and chemical aspects for their external protection such as an outer membrane. The presence of the outer membrane inhibits the absorption of the Gram stain dye; a dye used to detect bacterium’s susceptibility to certain antibiotics.
The external membrane is also significant in the bacteria’s interaction with a host organism. The external membrane of Gram-negative bacteria prevents host immune cells from recognising the bacteria as an ‘enemy’ as the coating mimics the victim’s own cells. The extra layer is also an effective defence against most common antibiotics. Able to evade attacks of the infected host’s immune defence and antibiotics, Gram-negative bacteria pose a very dangerous threat.
Willis’ team targeted the cellular methods and machinery Gram-negative bacteria use to create their external membrane. With the goal of understanding the complex pathways of the membrane, the researchers analyzed the various associated molecules and enzymes. Previous research had analyzed individual components, unable to examine links within the targeted molecule. Willis’ team was able to develop a new technique to successfully analyze links to provide insight to the overall structure of the molecule in question. The molecule, though common between several species of Gram-negative bacteria, is unique to bacteria. The discovery of the precise structure of the molecule will facilitate the creation of a drug that may use the analyzed molecule as a target to segregate otherwise camouflaged bacteria from the host’s native cells. “It would be a new kind of antibiotic,” Willis stated in a press release, discussing the potential for her team’s research.
Funded through the Natural Sciences and Engineering Research Council and Canadian Institutes of Health Research, and by Dr. Whitfield’s Canada Research Chair in Molecular Microbiology, the research creates potential for breakthrough developments in drugs. “Without these enzymes, the cell can’t make these complex sugars and can’t assemble the surface coat,” said Whitfield. “If you’re able to target the initial enzyme, you turn the entire process off.” The molecular target specific to bacteria, and essential to the production of the Gram-negative coating may allow drugs to limit the creation of the external membrane and allow the host immune system to find and destroy the invading organisms. Understanding the creation of the Gram-negative membrane is a crucial step in the research and development of tools in the combat against harmful microorganisms.