Recent research conducted by researchers from Yale University is published in Applied and Environmental Microbiology, suggesting that natural bacteriophage, or phage, can kill dysentery-causing bacteria and reduce virulence in surviving bacteria. It's a piece of inspiring news as treating dysentery has become a challenge with the rising antibiotic resistance.
Background
Shigella flexneri, the culprit causing contagious infection marked by inflammatory diarrhea and dysentery in sub-Saharan Africa and southern Asia, kills about 160,000 people globally every year. The World Health Organization (WHO) takes priority to this pathogen in terms of increasing cases, antimicrobial resistance, and limited treatment options.
S. flexneri is active primarily in low-income countries, like southern Asia and sub-Saharan Africa. In these places, dirty drinking water is a concern causing dysentery, while antibiotics are expensive and unavailable, not to mention the condition that the bacteria have already developed resistance to conventional antibiotics.
Research
Scientists at Yale University collected water in Cuatro Cienegas, Mexico, a region renowned for its extreme microbial biodiversity. They have successfully isolated a novel lytic phage that uses the OmpA porin of S.flexneri as a receptor. This is a natural bacteriophage named A1-1, and it can infect and break down the resistant and mutant Shigella bacteria. This study using phenotypic assays and genome sequencing has shown that this naturally occurring phage can kill Shigella flexneri and select phage-resistant mutants, including OmpA-deficient mutants and LPS-deficient mutants with reduced virulence. It demonstrates the potential benefits of phage-based therapy to fight human bacterial infections.
Researchers at Yale comment it as "a biomedically useful evolutionary tradeoff that improves upon standard phage therapy approaches" and hold that the A1-1 phage might even be useful for treating water sources, by selecting for avirulent S. flexneri."
Phage Therapy
Phages are viruses that infect bacteria, so they are gradually discovered as natural enemies of bacteria. The property of only attacking specific bacteria and being harmless to people, animals, and plants makes phages promising treatment, especially in the case of rising resistance to antibiotics.
Approaches of phage therapies include:
l Monophage therapy using a single phage type as a therapeutic agent, which is based on a precise matching between the pathogen and the phage.
l Polyphage therapy using combined phages as therapeutic agents, which can target multiple strains of a single bacterial species or multiple species.
l Bio-engineered phage therapy using genetically engineered phages, which can be used to deliver therapeutic agents into target bacterial cells.
Unmodified Bacteriophages
Naturally occurring phages are unmodified or non-engineered bacteriophages. Besides applications in treating infectious diseases, they have been widely used as powerful label-free bacterial sensors for pathogen detection. Combined with innovative detector platforms showing interactions between phages and host bacteria, unmodified phages can be used to identify the natural infection cycle of phages, such as attachment to the host cell, penetration to inject nucleic acid, biosynthesis of proteins and nucleic acids, virion assembly to form the phage progeny, and host cell lysis, and the release of phage progeny.
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