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Phages encode lysins to break down the bacterial cell wall

Phages use lysins every day to kill bacteria

 

Phages are the most abundant biological entity on earth. Approximately 10³¹ populate our planet and they outnumber bacteria 10:1. Phages hunt, infect and kill bacteria and are extremely precise – typically only capable of infecting a small number of bacterial strains.

 

Phages are bactericidal by nature as they need to escape their host at the end of the replication cycle. To cleave open the bacterial cell wall, they encode proteins called lysins. These are cell-wall cleaving enzymes that break chemical bonds in the bacterial cell wall. Once the cell wall is breached, the bacteria irreversibly dies.

 

But lysins can also cleave the cell wall from the outside. This makes them a novel class of anti-bacterials with the potential to revolutionize the treatment of bacterial infections. They also retain the precision of the phage that originally encoded them, meaning that the lysins only kill selective groups of bacteria. This makes them ideal drug candidates for microbiome interventions as well as to develop a new class of precision anti-bacterials.

See below for a schematic representation of how phages use lysins in nature to kill bacteria.

Lysins are expressed in the final step of the phage replication cycle

Phage infection

Phages hunt for a specific bacteria to infect

Phage assembly

Phages hijack the bacteria to produce new phage particles

Lysin assembly

Phages force the bacteria to assemble cell wall lysins

Cell destruction

Lysins cleave the cell wall, the new phage particles escape

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Lysins as pharmaceuticals

The potential of lysins as novel anti-bacterials have been well recognized over the past decades. However natural lysins have faced a number of challenges:

  • Limited availability: for many target pathogens, phages their natural lysins are not known

  • Limited potency: lysins in nature are not optimized for perfect potency

  • Limited drug properties: natural lysins are not optimized for specific drug settings

 

PhagoMed discovers, optimizes and develops synthetic lysins. These synthetic lysins are predicted in-silico and are possible for any pathogen as well as vastly superior to natural lysins.

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TED Talk on phages

    For further background on phages, watch PhagoMed CEO Alexander Belcredi talk about the history of phages, their biology and why phages can be a solution for the antibiotics crisis.