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Title: Engineered lysins with customized lytic activities against enterococci and staphylococci
Authors: Hana Sakina Muhammad Jai
Dam, Linh Chi
Tay, Lowella Servito
Koh, Jodi Jia Wei
Loo, Hooi Linn
Kline, Kimberly A.
Goh, Boon Chong
Keywords: Science::Biological sciences
Issue Date: 2020
Source: Hana Sakina Muhammad Jai, Dam, L. C., Tay, L. S., Koh, J. J. W., Loo, H. L., Kline, K. A., & Goh, B. C. (2020). Engineered lysins with customized lytic activities against enterococci and staphylococci. Frontiers in Microbiology, 11, 574739-. doi:10.3389/fmicb.2020.574739
Journal: Frontiers in Microbiology 
Abstract: The emergence of multidrug-resistant bacteria has made minor bacterial infections incurable with many existing antibiotics. Lysins are phage-encoded peptidoglycan hydrolases that have demonstrated therapeutic potential as a novel class of antimicrobials. The modular architecture of lysins enables the functional domains – catalytic domain (CD) and cell wall binding domain (CBD) – to be shuffled to create novel lysins. The CD is classically thought to be only involved in peptidoglycan hydrolysis whereas the CBD dictates the lytic spectrum of a lysin. While there are many studies that extended the lytic spectrum of a lysin by domain swapping, few have managed to introduce species specificity in a chimeric lysin. In this work, we constructed two chimeric lysins by swapping the CBDs of two parent lysins with different lytic spectra against enterococci and staphylococci. We showed that these chimeric lysins exhibited customized lytic spectra distinct from the parent lysins. Notably, the chimeric lysin P10N-V12C, which comprises a narrow-spectrum CD fused with a broad-spectrum CBD, displayed species specificity not lysing Enterococcus faecium while targeting Enterococcus faecalis and staphylococci. Such species specificity can be attributed to the narrow-spectrum CD of the chimeric lysin. Using flow cytometry and confocal microscopy, we found that the E. faecium cells that were treated with P10N-V12C are less viable with compromised membranes yet remained morphologically intact. Our results suggest that while the CBD is a major determinant of the lytic spectrum of a lysin, the CD is also responsible in the composition of the final lytic spectrum, especially when it pertains to species-specificity.
ISSN: 1664-302X
DOI: 10.3389/fmicb.2020.574739
Rights: © 2020 Binte Muhammad Jai, Dam, Tay, Koh, Loo, Kline and Goh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SCELSE Journal Articles

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