Improved treatments for infections caused by often-deadly antibiotic-resistant bacteria may result from a recent discovery by University of Guelph microbiologists.
By studying how methicillin-resistant Staphylococcus aureus (MRSA) colonizes and infects human hosts, the researchers have found a potential drug target to strengthen existing treatments to overcome antimicrobial resistance (AMR).
Their paper appears online this week in the Proceedings of the National Academy of Sciences.
An urgent public health threat that has been called a “silent pandemic,” infections caused by drug-resistant pathogens including MRSA are estimated to have caused more than 1.2 million deaths worldwide in 2019, said Dr. Georgina Cox, a professor in the Department of Molecular and Cellular Biology within the College of Biological Science.
Referring to drug-resistant strains of bacteria, she said, “The more we use antibiotics, the more selective pressure there is for resistance to those drugs. It’s a major problem.”
The new paper describes the team’s finding that a compound can block the activity of a key bacterial enzyme enabling the pathogen to stick to host cells. Co-authors are scientists at U of G, Western University and the University of Victoria.
Research targets bacterial proteins that enable infection
Their research helps explain a longstanding mystery for scientists: how do a microbe’s so-called “adhesion” proteins get through the bug’s tough cell wall to end up as sticky surface attachments that latch onto host cells during infection?
The researchers showed that these proteins rely on other bacterial enzymes called autolysins to chew a path to the outside, like a snowplow clearing the way for traffic. Without these autolysins, the microbe remains “naked” and unable to cling to the host, said Cox.
Scientists already knew that microbial autolysin played a role in cell adhesion, but they didn’t know how. Besides teasing out the role of this enzyme, the U of G-led team found that an autolysin-blocking drug compound called complestatin affected early stages of infection in mice exposed to MRSA.
Cox said this finding might help treat infections caused by pathogens in two ways. Besides preventing host adhesion and invasion, drugs may also keep the microbe from “hiding” in host cells from other kinds of antibiotics and the body’s immune system.
“This could be a one-two punch,” said lead author Allison Leonard, a PhD candidate in Cox’s lab who completed her B.Sc. at U of G in 2019.
Explaining that the approach offers a new way of thinking about fighting drug-resistant infections, Leonard said, “These compounds could be combined with other antibiotics as adjuvant therapies or used alone.”
Leonard has also developed a test for identifying S. aureus genes enabling the bug to stick to different surfaces within the body.
This research was supported by funding from the Canadian Institutes of Health Research.
Dr. Georgina Cox