McMaster researcher Lori Burrows (left) and postdoc Nathan Roberge (right) have discovered the broad antibacterial effects of a phage-based protein.
Photo Credit: Courtesy of McMaster University
Scientific Frontline: Extended "At a Glance" Summary: Phage Protein Aqs1 and Bacterial Disarmament
The Core Concept: Researchers have discovered that Aqs1, a specialized protein produced by bacteriophages, can broadly disable the infectious capabilities of multiple disease-causing bacteria by shutting down their structural machinery.
Key Distinction/Mechanism: While the specific phage that produces Aqs1 naturally infects only Pseudomonas aeruginosa, the protein itself targets a conserved molecular region shared across many pathogenic species. Aqs1 jams the engine responsible for producing type IV pili, preventing the bacteria from moving, adhering to host tissues, and receiving subsequent viral infections.
Major Frameworks/Components:
- Bacteriophages: Viruses that exclusively infect and replicate within specific bacterial hosts.
- Aqs1 Protein: The viral protein expressed during infection that suppresses bacterial pili production.
- Type IV Pili: Fibrous, hair-like appendages on the bacterial surface essential for motility, adhesion, and pathogenesis.
- Pseudomonas aeruginosa: A multidrug-resistant pathogen that serves as the natural host for the Aqs1-producing phage.
Branch of Science: Microbiology, Molecular Biology, and Infectious Diseases.
Future Application: This structural mechanism lays the groundwork for developing novel, broad-spectrum antimicrobial therapeutics that mimic the Aqs1 protein to disarm, rather than directly kill, multidrug-resistant bacteria.
Why It Matters: As global antibiotic resistance accelerates, exploiting conserved structural vulnerabilities shared among diverse bacterial species offers a highly promising new strategy for treating persistent infections without traditional bactericidal agents.
Researchers at McMaster University have discovered that a protein produced by phages—viruses that infect bacteria—can disarm multiple disease-causing bacteria, which could have implications for the development of future antimicrobial therapies.
The new findings, published recently in the journal PLOS Pathogens, are a one-two punch: they not only reinforce the promise of phage-based approaches to fighting bacterial infections but also reveal a broad new vulnerability in bacteria that researchers could one day exploit with new medicine.
“This phage that we studied has effectively exposed a new weakness that is shared by several different types of bacteria,” explains Lori Burrows, professor emerita at McMaster and principal investigator on the new study. “That this protein affects such different bacteria suggests that new drugs that mimic its effects could help treat a broad spectrum of infections.”
The protein, called Aqs1, shuts down the molecular machinery that allows bacteria to build fibrous structures that are essential to their survival.
Those structures, called type IV pili, are tiny, hair-like fibers found on many bacteria, including multidrug-resistant Pseudomonas aeruginosa. Pili help Pseudomonas and other bacteria move around, stick to surfaces and host tissues, and carry out other functions that contribute to disease. But pili are also a liability for bacteria, providing an entry point through which phages can infect them.
In the case of Pseudomonas, certain phages express Aqs1 once inside the bacteria, which jams the engine behind pili production and function. In doing so, the phages effectively cut off access to the outside world, allowing them to harbor their hosts for themselves.
“Phages are selfish,” explains Burrows. “They want the bacteria all to themselves, so once they get inside, they stop them from making and using pili so that no other phages can get in.”
This process is not only beneficial to the phage but also to medicine—it weakens the bacteria’s ability to colonize hosts and cause infection, which Burrows says is indicative of the overall promise of using phages as therapeutics.
While Aqs1 was previously known to interfere with pili production in Pseudomonas, Burrows’s team hypothesized that it might also affect related systems that are widely found in other pathogenic bacteria, including some of critical concern.
To test their theory, the research team, led by postdoctoral fellow Nathan Roberge at the Michael G. DeGroote Institute for Infectious Disease Research, introduced the protein to other pili-producing bacteria.
Although these specific phages don’t naturally infect anything outside of Pseudomonas—phages are highly specialized and typically recognize only very specific bacterial hosts—the researchers wanted to know if Aqs1 was targeting something unique to Pseudomonas or if it was exploiting a feature shared across different bacteria.
“What we found was that the phage protein targeted a specific region of related proteins found in many different pili-producing bacteria,” says Roberge, who first-authored the new study. “So, even though the phage that produces Aqs1 is specific to Pseudomonas, the protein itself is still able to recognize similar machinery in other bacteria.”
Roberge says the findings lay the groundwork for the development of new antimicrobial strategies that borrow Aqs1’s approach, targeting pili function across multiple disease-causing bacteria.
Reference material: What Is: Bacteriophages
Funding: This study was supported in part by funding from the Canadian Institutes of Health Research and the National Institutes of Health.
Published in journal: PLOS Pathogens
Title: A broad-spectrum phage-encoded mechanism to disarm bacterial type IV filaments
Authors: Nathan A. Roberge, Paankhi Dave, Véronique Taylor, Taylor J. Ellison, Callum Myers, Courtney K. Ellison, Karen L. Maxwell, and Lori L. Burrows
Source/Credit: McMaster University | Blake Dillon
Edited by: Scientific Frontline
Reference Number: mcb080426_01