The CD27L and CTP1L Endolysins Targeting Contain a Built-in Trigger and Release Factor

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Clostridium difficile infection is a common cause of hospital-acquired diarrhea, following broad-spectrum antibiotic treatment particularly in elderly patients. Bacteriophage therapy could provide an alternative treatment, but a better understanding of the viral components that lyse the bacterial cell is necessary. Here, we report on the activation of two endolysins from bacteriophages that lyse Clostridia. The structures of autoproteolytic fragments of two endolysins were determined by X-ray crystallography. Based on the structures, we introduced mutations that affect the autolytic cleavage of the enzymatic portion of the endolysins, and we show that two oligomeric states have an effect on the cleavage mechanism. Moreover, the lysis activity is affected when autocleavage is inhibited for one endolysin. We propose that the cleavage and oligomerization are linked, and they provide the endolysin with a trigger and release mechanism that leads to activation. The identification of a trigger and release factor may not only be relevant to Clostridia endolysins, but could be an important factor in the triggering of many bacteriophage endolysins. A fuller understanding of this activation mechanism will help in the design of recombinant endolysins or bacteriophages with a more efficient therapeutic potential.

Vyšlo v časopise: The CD27L and CTP1L Endolysins Targeting Contain a Built-in Trigger and Release Factor. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004228
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004228

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