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Bacteria versus viruses

As antibiotic resistance challenges scientists to find new ways to treat bacterial infections, researchers at Michigan State University have discovered a new way for bacteria to defend themselves against viral infection, known as phage, which could lead to better treatments in the future. The research was recently published in the journal Nature Microbiology.

Chris Waters, MSU professor of microbiology.
Chris Waters, MSU professor of microbiology, and his team have discovered a new way for bacteria to defend themselves against viral infection, known as phage, which could lead to better treatments in the future. Credit: Derrick Turner

When bacteria are resistant to antibiotics, phage therapy has become an effective way to treat bacterial infections. Phage therapy uses a bacterial phage to infect and kill the bacteria.

While studying the evolution of the cholera-causing bacteria Vibrio cholerae, MSU microbiologist Chris Waters, along with graduate student Brian Hsueh and Geoff Severin (now a postdoctoral fellow at the University of Michigan), discovered that bacteria have developed a new defense mechanism against phage infection they named AvcD.

“This bacterial defense system is analogous to the viral defense system present in humans to inhibit viruses like HIV,” said Waters, a professor in the Department of Microbiology and Molecular Genetics (MMG) in the colleges of Natural Science and Osteopathic Medicine. “By understanding how bacteria prevent phage infection, we can predict and counteract the mechanisms that will allow bacteria to resist emerging phage therapy approaches to treat antibiotic-resistant infections.”

When the enzyme AvcD is turned “on,” it depletes nucleotides, which are the building blocks of DNA, in the cell. This prevents the cell from growing and replicating more phage that normally would kill the host bacteria. It also reduces the number of phage that can burst from the cell to infect its neighbors, saving the entire population of bacteria.

The micrographs above show that activation of AvcD causes normal bacterial cells (left) to form long filaments (right) due to depletion of nucleotides.
The micrographs above show that activation of AvcD causes normal bacterial cells (left) to form long filaments (right) due to depletion of nucleotides. Credit: Chris Waters lab

“If this enzyme was activated in the cell all the time, it would be toxic,” Waters said. “To save neighboring cells, the bacteria make an RNA (called AvcI) which binds to AvcD and prevents it from depleting all the nucleotides in the cell.”

The researchers showed that once bacteria are infected with a phage, the AvcI in the cell breaks down, which activates the AvcD gene to inhibit phage production.

Additional MSU collaborators on the project are J.K. Billman, Jr., M.D. Endowed Research Professor Kristin Parent (Biochemistry and Molecular Biology) and Assistant Professor Janani Ravi (MMG). 

 

Banner image: Vibrio cholerae (pictured above) is a species of Gram-negative, facultative anaerobe and comma-shaped bacteria. Some strains of V. cholerae are pathogenic to humans and cause a deadly disease cholera, which can be derived from the consumption of undercooked or raw marine life species. Credit: CDC Public Health