Phages are viruses that infect micro organism and can be used to deal with human infections. However, as with antibiotics, micro organism can readily evolve resistance to phage assault, highlighting a key limitation to using phages as therapeutics. Now, researchers from Yale University have proven that the naturally occurring phage A1-1 kills Shigella flexneri, a significant explanation for dysentery in sub-Saharan Africa and southern Asia and selects for phage-resistant mutants with lowered virulence. The analysis is revealed in Applied and Environmental Microbiology.
That serendipitous discovering outcomes from the truth that the phage‘s use of a specific floor receptor on the bacterium referred to as OmpA, as a portal to enter and kill S. flexneri, implies that micro organism that escape the phage’s assault will both lack OmpA receptors, or that any remaining receptors can have mutated in ways in which scale back virulence.
“We sought to discover a phage that was naturally capable of binding to outer membrane proteins of S. flexneri responsible for virulent cell to cell spread of this pathogen in the human intestine, hypothesizing that evolution of phage resistance should alter, or eliminate, this virulence factor protein,” stated Kaitlyn E. Kortright, a postdoctoral scientist at Yale.
This, stated Kortright, is “a biomedically useful evolutionary tradeoff that improves upon standard phage therapy approaches.”
The researchers pursued phage remedy towards S. flexneri as a result of that bacterium was already resistant to traditional antibiotics. Additionally, this pathogen is lively primarily in low-income international locations, the place antibiotics are costly and sometimes unavailable, and clear ingesting water is scarce. Phages, she defined, “might even be useful for treating water sources, by selecting for avirulent S. flexneri.”
The investigators started this challenge not figuring out whether or not or not a phage existed that may kill S. flexneri. They assumed “that such viruses had naturally evolved, and could be isolated from environmental samples,” stated Paul E. Turner, the Rachel Carson Professor of Ecology and Evolutionary Biology at Yale. To enhance the chances, “we chose to search in a geographic region renowned for its extreme microbial biodiversity: Cuatro Cienegas, Mexico. Clearly a longshot, but apparently a reasonable idea, because this effort was successful.”
Kaitlyn E. Kortright et al, Selection for phage resistance reduces virulence of Shigella flexneri, Applied and Environmental Microbiology (2021). DOI: 10.1128/AEM.01514-21
American Society for Microbiology
Phages kill dystentery-causing micro organism and scale back virulence in surviving micro organism (2021, November 19)
retrieved 19 November 2021
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