Towards phage therapy against Staphylococcus aureus: investigating anti-defense strategies of Kayvirus phages

Staphylococcus aureus is a human pathogen responsible for numerous infections, including nosocomial infections. It is one of the leading causes of deaths linked to antibiotic resistance. The World Health Organization has classified it as a high-priority pathogen for which alternatives to antibiotics should be developed urgently. In this context, phage therapy has emerged as a promising approach to tackle this major global health concern.

Two young researchers, Dr. Audrey Leprince and Luka Mairet, have recently joined the team of Prof. Gipsi Lima Mendez at UNamur (URBM) to launch a research project focusing on phages from the Kayvirus genus, which are ideal for phage therapy in the context of S. aureus infections. These phages are of particular interest due to their broad host range, enabling them to infect a wide variety of S. aureus strains. This versatility is largely explained by their ability to recognize conserved structures on the bacterial cell wall, which facilitates attachment to multiple strains. However, successful infection involves more than just attachment. Once phage DNA has been injected into the host cytoplasm, S. aureus can activate intracellular defense systems that hinder the phage replication cycle. However, the strategies evolved by Kayvirus phages to bypass bacterial immune responses and ensure efficient infection have not been investigated in detail.

The aim of this project is to uncover how Kayvirus phages overcome the intracellular defenses of S. aureus. The research focuses in particular on identifying viral proteins that trigger host defense activation, as well as anti-defense proteins that inhibit these systems.

Dr. Audrey Leprince brings strong expertise in bacteriophage biology. She earned her PhD from the UCLouvain, where she studied adsorption and lysis processes of bacteriophages infecting members of the Bacillus cereus group in Prof. Jacques Mahillon's lab. She then completed a postdoctoral fellowship at University Laval in Canada, working on Streptococcus thermophilus defense systems against phage infections in the dairy industry, under the supervision of Prof. Sylvain Moineau. Audrey has now joined UNamur thanks to an FNRS postdoctoral grant to pursue this new project.

She is joined by Luka Mairet, who has a master’s degree in Molecular and Cellular Biology, with a specialization in virology, from Université Paul Sabatier Toulouse III in France, and who has recently started a doctoral thesis at UNamur.

Ultimately, their research will deepen our understanding of phage–bacteria interactions, paving the way for the development of innovative phage-based therapeutic solutions.

From left to rigth: Luka Mairet, Gipsi Lima Mendez and Audrey Leprince