Project Details
Projekt
Glycocode-guided bacteriophage-host interaction in the evolution of the genus Staphylococcus
Applicant
Professor Dr. Andreas Peschel
Subject Area
Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
Microbial Ecology and Applied Microbiology
Microbial Ecology and Applied Microbiology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 465126486
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 the facultative pathogens Staphylococcus aureus and Staphylococcus epidermidis can alter the species- and strain-specific structure of wall teichoic acid (WTA) glycopolymers, the major staphylococcal phage binding structures at the bacterial surface, to shape the susceptibility to specific phages. The pathway of WTA glycosylation in the coagulase-negative Staphylococcus (CoNS) species S. epidermidis was unraveled, yielding important insights into the receptor preferences of phages specific for S. epidermidis and other CoNS species. WTA glycosylation by different hexoses turned out to be particularly crucial for binding of specific phage groups and staphylococcal genomes differed in sets of WTA glycosyl transferases. We also analyzed the receptor-binding proteins (RBPs) of major Staphylococcus phage groups and developed an RBP-based typing method that helps to predict the phage specificities of opportunistic CoNS pathogens. We found that S. epidermidis and potentially other CoNS use at least two glycosylation pathways for WTA modification with different sugars. We will identify alternative glycosylation pathways and their regulation to achieve a comprehensive understanding of CoNS phage susceptibilities under different environmental conditions including invasive infections. Our computational phage analysis tool PhARIS will be expanded to predict phage receptor specificities in a wider range of staphylococcal opportunistic pathogens. Currently unknown phages with the capacity to transduce resistance genes from CoNS to S. aureus will be identified. 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. Our project will also be of relevance for future phage therapy approaches and for the individual design of phage cocktails adjusted to specific pathogen clones.
DFG Programme
Priority Programmes
