Decoding the Molecular Properties of Mycobacteriophage D29 Holin Provides Insights into Holin Engineering
Varun Rakeshbhai Bavda, Aditi Yadav, Vikas Jain
Abstract
Holins are bacteriophage-encoded small membrane perforators that play an important role in determining the timing of host cell lysis towards the end of the phage infection cycle. Holin's ability to precisely time the hole formation in the cell membrane ensuing cell lysis is both interesting and intriguing. Here, we examined the molecular properties of the mycobacteriophage D29 Holin C-terminal region that harbours several polar charged residues and a coiled-coil domain. Our data allowed us to engineer Holin with an ability to rapidly kill bacteria and show higher toxicity than the wild-type protein. Due to their ability to kill host bacteria by membrane disruption, it becomes important to explore the molecular properties of Holins that allow them to function in a timely and efficient manner. Understanding these details can help us modulate Holin activity and engineer bacteriophages with superior lytic properties to kill pathogenic bacteria, curtail infections, and combat antimicrobial resistance.