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       Study underscores new strategies to fight drug-resistant bacteria
        
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       Several billion years ago, a genetic arms race began between bacteria
       and their viral killers. This seemingly eternal struggle continues
       today, with implications for diseases killing tens of thousands of
       people around the world each year.
        
       A recent study published in Science reveals key insights into how
       bacteria killers called bacteriophages or phages impact the severity
       of the waterborne diarrheal disease cholera. Cholera kills between
       21,000 and 143,000 people annually worldwide. It is a disease of
       poverty, striking regions lacking clean drinking water and sanitation.
        
       The team, including McGill Microbiology and Immunology Professor Jesse
       Shapiro, conducted what it believes to be one of the largest genetic
       studies to analyze the dynamic relationship between cholera bacteria,
       their bacteriophages and antibiotics.
        
       The study underscores the possibility of creating new strategies to
       use bacteriophages to kill drug-resistant bacteria in cholera and
       other diseases that have plagued civilization for centuries. It
       revealed a pathway to new diagnostics and antibiotic resistance
       mitigation.
        
       "Cholera is a devastating waterborne infection that causes millions of
       cases and thousands of deaths each year, with risk expected to
       increase with climate change. Antibiotic resistance is also an
       increasing concern and alternative anti-infection treatments are
       needed," said Shapiro.
        
       ## Effective predation
        
       A key finding involves a concept called "effective predation." The
       researchers found a higher ratio of phage predators to their bacterial
       prey was associated with milder cholera cases. The team said it is the
       first to show the genetic underpinnings of this ratio.
        
       This ratio can be used as a marker of disease severity, informing a
       physician's decisions on treatment. It might also predict disease
       progression.
        
       The researchers used advanced genomic techniques to analyze the
       interaction of bacteria and the bacteriophages in 2,574 stool samples
       from cholera patients in Bangladesh, a nation with one of the world's
       highest cholera rates — about 100,000 cases yearly. Samples were
       collected in 2018 and 2019.
        
       Shapiro conducted a genetic analysis of samples with the study's lead
       author, Naïma Madi, Ph.D., a postdoctoral researcher at McGill.
        
       Documenting the genetic arms race between the bacterium and its phages
       complicates the study of cholera and phage ecology. Each evolves to
       thwart the other's defenses. One adapts, the other responds. If the
       phages have the upper hand, the genetic diversity of the bacteria
       increases. Then, the population of phages falls. The virus responds
       with genetic adaptations, eventually thriving again.
        
       Shapiro said more studies, including a clinical trial, are needed
       before effective phage therapies are developed. The study, among
       several other sources, received support from the National Institutes
       of Health and the Canadian Institutes for Health Research Project.
        
       ## About the study
        
       Phage predation, disease severity, and pathogen genetic diversity in
       cholera patients by Naïma Madi, Jesse Shapiro et al., was published in
       _Science._
        
        
        
        
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