The most intense co-evolution on our globe takes place between bacteria and their viruses, called
bacteriophages. Bacteriophages kill their bacterial host with a very high specificity. Every phage
infection is initiated by the recognition of a specific structure on the bacterial surface by a receptorbinding
protein (RBP). Some phages having a single RBP, infect only one specific bacterial serotype,
while others can attack different bacterial hosts, recognized by different RBPs. Jumbo phages are
very large in size and equipped with multiple RBPs assembled in a flower-like structure.
Consequently, they can infect multiple bacteria, rendering these phages very interesting for therapy.
Phage therapy is a long known concept, but only recently regaining high interest. Phages are then
used to treat multidrug-resistant bacterial infections. Most jumbo phages have been discovered only
recently and many features of their functionality remains unknown. One of the important aspects is
how their complex flower-like RBP structure is organized, functions, and evolves, and how the
bacterial host responds to jumbo phages with such complex host recognition apparatus, compared to
their response to simple phages. We will elaborate these topics on two Klebsiella specific jumbo
phages on three levels: the protein level, the phage level and the bacterium-phage interaction level,
using advanced molecular microbiology, synthetic biology, and structural methods.