Glycocode-guided bacteriophage-host interaction in the evolution of the genus Staphylococcus

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The various Staphylococcus species encounter a huge variety of phages in their natural habitats, the human nasal cavity and skin. Being susceptible to specific phages has its ‘pros and cons’ – it governs the vulnerability to phage killing but also the access to a common genetic pool of a species because phages are the major vehicle of horizontal gene transfer in staphylococci. Indeed, the ongoing evolution of new antibiotic resistance, virulence, and fitness traits of the genus is governed by transducing phages. We found that Staphylococcus aureus and Staphylococcus epidermidis alter the species- and strain-specific structure of wall teichoic acid (WTA) glycopolymers at the bacterial surface to shape the susceptibility to specific phages. WTA glycosylation by different hexoses turned out to be particular crucial for binding of specific phage groups and staphylococcal genomes differed in sets of WTA glycosyl transferases. We also characterized WTA-binding proteins at phage base plates to elucidate structure-function relationships. We propose to systematically identify and characterize WTA glycosyl transferases of different Staphylococcus species, elucidate their impact on intra- and interspecies horizontal gene transfer, and correlate glycosylation patterns with the structure of corresponding phage binding proteins. These tools will allow us to identify new transducing phages, which can connect the genetic pools of S. aureus and coagulase-negative staphylococci such as S. epidermidis. Such phages could be responsible for the continuous import of resistance and virulence genes into S. aureus thereby driving the evolution of this major human pathogen. Molecular investigations on the interaction of phage proteins that bind species-specific, glycosylated WTA will yield a comprehensive map of the glycocodes of Staphylococcus-phage interaction with important implications for the ongoing processes of pathogen evolution.