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Page 14 of 16               Varming et al. Microbiome Res Rep 2024;3:15  https://dx.doi.org/10.20517/mrr.2023.50

               infections. Furthermore, similar lysogeny switches as in φ13 have been detected in several streptococcal and
                                [21]
               enterococcal species , where prophages are also increasingly linked to pathogenesis [38,39] ; thus, a molecular
               understanding of such Mor-containing switches has even wider implications.

               DECLARATIONS
               Acknowledgments
               Thanks to Yusuf Theibich, Mohannad Aloula, and Sanchari Banerjee (University of Copenhagen) for help
               running the isoelectric focusing electrophoresis, the crystallization robot and synchrotron data collection,
               respectively. The authors acknowledge the European Synchrotron Radiation Facility for the provision of
               beam time on ID23-2 and they would like to thank local contact Basu Shibom for assistance in remote data
               collection at the beamline. Huang Z and Lo Leggio L are members of ISBUC, Integrative Structural Biology
               at the University of Copenhagen (www.isbuc.ku.dk).

               Authors’ contributions
               Made substantial contributions to the conception and design of the study: Varming AK, Rasmussen KK,
               Kilstrup M, Ingmer H, Lo Leggio L
               Carried out protein purification: Varming AK, Rasmussen KK
               Carried out all biochemical work on φ13 CI and Mor and made the related figures: Varming AK
               Carried out crystallization: Hamad GM
               Determined, refined, and deposited the crystal structure of CI-NTD: Huang Z
               Carried out all computational modeling and structural analysis: Lo Leggio L
               Made structural figures: Huang Z, Lo Leggio L
               Wrote the manuscript draft: Varming AK, Lo Leggio L, Huang Z
               Comments and additions to the manuscript draft: Kilstrup M, Ingmer H, Rasmussen KK

               Availability of data and materials
               The TP901-1 and CI-NTD crystal structure and related data were deposited at the Protein Data Bank with
               code 8QAO. The computational model for φ13 CI-NTD:Mor complex is available in Supplementary
               Materials.


               Financial support and sponsorship
               This work was supported by a Lundbeck Foundation PhD scholarship to AKV (R249-2017-977) and an
               Independent Research Fund Denmark project grant “Molecular mechanisms and structural dynamics in the
               TP901-1 genetic switch and related pathogen systems” (DFF - 4002-00107). The structure of CI-NTD was
               elucidated during the development of a course on Integrative Structural Biology at University of
               Copenhagen, funded by an educational initiative of the Novo Nordisk Foundation (grant NNF22SA0076513
               to Kresten Lindorff-Larsen). We thank the Danish Agency for Science, Technology, and Innovation for
               funding the instrument center DanScatt.

               Conflicts of interest
               All authors declared that there are no conflicts of interest.

               Ethical approval and consent to participate
               Not applicable.

               Consent for publication
               Not applicable.
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