Characterizing a Chimera: Comparative Analysis of Pal Endolysin and its Homologs

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Once a virus infects a cell and produces more virus particles (virions), it must find a way to release those virions so they can infect more cells. Bacteriophage, or viruses that infect bacteria, accomplish this goal by producing endolysins, proteins that cause bacterial cells to lyse by breaking down their cell walls. Many endolysins have a modular structure consisting of an enzymatically active domain (EAD), which catalytically breaks bonds in peptidoglycan, the main component of bacterial cell walls, and a cell wall binding domain (CBD), which attaches the endolysin to the cell wall and determines host specificity. By combining EADs and CBDs from different endolysins, researchers can produce new “chimeric” endolysins in order to kill disease-causing bacteria in a targeted fashion, which can be more effective than the original enzymes. Chimeric endolysins can also form naturally. Bacteriophage Dp-1, which infects Streptococcus pneumoniae bacteria, produces a chimeric endolysin called Pal. Pal’s CBD has the ability to bind to choline and is very similar to a portion of the LytA enzyme produced by S. pneumoniae. Pal’s EAD breaks down amide bonds in peptidoglycan and is very similar to a portion of the endolysin produced by a Bacteriophage BK5-T, which infects Lactococcus lactis bacteria. In our research, we used bioinformatics techniques to find other proteins that share homology with Pal and to investigate the evolutionary relationships between these proteins. We hope that a better understanding of this natural chimeric endolysin could be useful to researchers attempting to engineer new ones.