Project Details
Projekt
The role of phage Thanatos ADP-ribosyl-transferases Alt1 and Alt2 in disarming and preparing the host
Applicant
Professor Dr. Kai Thormann
Subject Area
Metabolism, Biochemistry and Genetics of Microorganisms
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 464874573
Bacteria and their viruses, known as phages, have coexisted in an ongoing battle for billions of years. Bacteria develop phage defense systems to fend off phage attacks, while phages evolve corresponding anti-defense strategies to successfully infect their host. Recent research has identified a multitude of novel phage defense systems to which phages have had to respond. ADP-ribosyltransferases (ADPRTs) are enzymes with various functions widespread in prokaryotes, eukaryotes, and viruses. Recent genome analyses reveal that many phages possess genes encoding ADPRTs. However, to date, only a few functions of ADPRTs (ModA, ModB, and Alt) from a single phage, the well-known Escherichia phage T4, are known. These enzymes NADylate or RNAylate host proteins involved in transcription and translation, thus participating in the reprogramming of the host cell. T4 Alt is located in the phage head and is injected into the target cell with or before the DNA, making ADPRTs powerful instruments to influence the host cell immediately after infection. Nevertheless, apart from T4, nothing is known about the ATP-ribosyltransferases of phages. Our model phage, Thanatos, which infects Shewanella oneidensis, possesses two Alt-like ADPRTs, Alt1 and Alt2. We have demonstrated that both proteins are present in the phage and actively modify target proteins immediately after phage infection. We have identified some potential target proteins that differ among Alt proteins and T4 Alt. These include proteins of cthe entral metabolism and also several potential phage defense systems, such as toxin-antitoxin systems or dNTPases. We postulate that Alt1 and Alt2 represent the phage's first line of attack to disarm the host and prepare it for the infection. Genetic modification of the alt genes in Phage Thanatos shows that both proteins are not essential for phage proliferation, but significantly enhance it. This work aims to further investigate the roles of the two ADPRTs, Alt1 and Alt2, of Phage Thanatos. The genetic accessibility of both phage and host provides an excellent platform outside of the known phage models. We expect to gain fundamentally new insights into the understanding of the role of phage ADPRTs in general and in the neutralization of phage defense systems in particular.
DFG Programme
Priority Programmes
