Nucleus-forming jumbophage PhiKZ therapeutically outcompetes non-nucleus-forming jumbophage Callisto

Ampapan Naknaen; Thanadon Samernate; Panida Saeju; Poochit Nonejuie; Vorrapon Chaikeeratisak

doi:10.1016/j.isci.2024.109790

Nucleus-forming jumbophage PhiKZ therapeutically outcompetes non-nucleus-forming jumbophage Callisto

iScience. 2024 Apr 18;27(5):109790. doi: 10.1016/j.isci.2024.109790. eCollection 2024 May 17.

Authors

Ampapan Naknaen¹, Thanadon Samernate², Panida Saeju¹, Poochit Nonejuie², Vorrapon Chaikeeratisak¹

Affiliations

¹ Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
² Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.

Abstract

With the recent resurgence of phage therapy in modern medicine, jumbophages are currently under the spotlight due to their numerous advantages as anti-infective agents. However, most significant discoveries to date have primarily focused on nucleus-forming jumbophages, not their non-nucleus-forming counterparts. In this study, we compare the biological characteristics exhibited by two genetically diverse jumbophages: 1) the well-studied nucleus-forming jumbophage, PhiKZ; and 2) the newly discovered non-nucleus-forming jumbophage, Callisto. Single-cell infection studies further show that Callisto possesses different replication machinery, resulting in a delay in phage maturation compared to that of PhiKZ. The therapeutic potency of both phages was examined in vitro and in vivo, demonstrating that PhiKZ holds certain superior characteristics over Callisto. This research sheds light on the importance of the subcellular infection machinery and the organized progeny maturation process, which could potentially provide valuable insight in the future development of jumbophage-based therapeutics.

Keywords: Biological sciences; Immunology.