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Varming et al. Microbiome Res Rep 2024;3:15 Microbiome Research
DOI: 10.20517/mrr.2023.50
Reports

Original Article Open Access

CI:Mor interactions in the lysogeny switches of
Lactococcus lactis TP901-1 and Staphylococcus

aureus φ13 bacteriophages

1
Anders K. Varming 1 , Zhiyu Huang 1 , Ghofran M. Hamad , Kim K. Rasmussen 1 , Hanne Ingmer 2 ,
Mogens Kilstrup 3 , Leila Lo Leggio 1

1
Department of Chemistry, University of Copenhagen, Copenhagen DK-2100, Denmark.
2
Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg DK-1870, Denmark.
3
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby DK-2800, Denmark.
Correspondence to: Prof. Leila Lo Leggio, Department of Chemistry, University of Copenhagen, Universitetsparken 5,
Copenhagen DK-2100, Denmark. E-mail: leila@chem.ku.dk
How to cite this article: Varming AK, Huang Z, Hamad GM, Rasmussen KK, Ingmer H, Kilstrup M, Lo Leggio L. CI:Mor
interactions in the lysogeny switches of Lactococcus lactis TP901-1 and Staphylococcus aureus φ13 bacteriophages. Microbiome Res
Rep 2024;3:15. https://dx.doi.org/10.20517/mrr.2023.50

Received: 28 Aug 2023 First Decision: 6 Nov 2023 Revised: 29 Dec 2023 Accepted: 9 Jan 2024 Published: 19 Jan 2024
Academic Editor: Douwe van Sinderen Copy Editor: Dong-Li Li Production Editor: Dong-Li Li

Abstract
Aim: To structurally characterize in detail the interactions between the phage repressor (CI) and the antirepressor
(Mor) in the lysis-lysogeny switches of two Gram-positive bacteriophages, the lactococcal TP901-1 and
staphylococcal φ13.

Methods: We use crystallographic structure determination, computational structural modeling, and analysis, as
well as biochemical methods, to elucidate similarities and differences in the CI:Mor interactions for the two genetic
switches.

Results: By comparing a newly determined and other available crystal structures for the N-terminal domain of CI
(CI-NTD), we show that the CI interface involved in Mor binding undergoes structural changes upon binding in
TP901-1. Most importantly, we show experimentally for the first time the direct interaction between CI and Mor for
φ13, and model computationally the interaction interface. The computational modeling supports similar side chain
rearrangements in TP901-1 and φ13.

Conclusion: This study ascertains experimentally that, like in the TP901-1 lysogeny switch, staphylococcal φ13 CI

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0
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