Rafal Mostowy
Jagiellonian University in Krakow
Malopolska Centre of Biotechnology
Rafal Mostowy is Associate Professor at the Jagiellonian University in Krakow and head of the Microbial Genomics Group at the Malopolska Centre of Biotechnology. His research focuses on the evolution of bacteriophages, with a particular emphasis on receptor-binding proteins (RBPs) and the molecular mechanisms driving phage adaptation and host specificity. By combining computational genomics, structural biology and evolutionary theory, his group investigates how genetic recombination shapes viral innovation, and what are the implications of this for bacteria-phage coevolution as well as the therapeutic use of phages. He is an EMBO Installation Grantee and a leader in the emerging field of phage bioinformatics.
Affiliations: (1). Malopolska Centre of Biotechnology, Jagiellonian University, Kraków (Poland) (2). Department of Pathogen Biology and Immunology, University of Wrocław, Wrocław (Poland) (3). Department of Infection Biology, London School of Hygiene & Tropical Medicine, London (UK) (4). Department of Life Sciences, Manchester Metropolitan University, Manchester (UK) (5). The Milner Centre for Evolution, Department of Life Sciences, University of Bath, Bath (UK) (6). Institut Pasteur, Université Paris Cité, CNRS, UMR(3525), Microbial Evolutionary Genomics, Paris (France)
Understanding the molecular basis of host range in Klebsiella pneumoniae phages is key to elucidating phage–bacteria co-evolution and guiding both ecological and therapeutic applications. Here, I present two complementary approaches focused on receptor-binding proteins (RBPs), each rooted in a distinct phage lifestyle. First, leveraging the lysogenic cycle, we conducted a genome-wide association study (GWAS) across an ecologically representative dataset of 2,527 Klebsiella genomes to identify prophage-encoded RBPs associated with capsule type. While classical beta-helix depolymerases were confirmed for a number of K-types, many GWAS hits belonged to enzymatically distinct families, notably SGNH hydrolases, suggesting capsule modification—not only degradation—may underlie infection. Second, we analyzed 192 lytic phage genomes sequenced during host range experiments. Here, via structural modelling, we found that depolymerases are mosaics in sequence and structure, enabling diverse enzymes to target the same capsule, and single enzymes to recognise multiple capsules. Furthermore, while most viruses carried expected depolymerases, 19% of them (n=36) lacked classical depolymerase folds, instead encoding SGNH hydrolyses or previously uncharacterized RBP structures. Altogether, these results point to a broader, underappreciated complexity in RBP–capsule interactions, underscoring the need for integrative approaches to predict and engineer phage host range.