Characterization of phage-mediated horizontal gene transfer in the human nose

• Applicant: Dr. David Gerlach
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 548397935

Staphylococcus aureus is a major human pathogen which causes a wide variety of infections. Phage-mediated horizontal gene transfer (HGT) is crucial for its adaptation to changing environments. Important lysogenic phages often encode virulence determinants providing fitness advantages to their staphylococcal host. The molecular details of staphylococcal phage biology, especially the interaction of staphylococcal phages with their host receptor, are increasingly understood. It has been shown that S. aureus can exchange genetic information not only with closely related staphylococci but also more distantly related bacteria via phage-mediated HGT. S. aureus is member of a complex microbiome, among them many other staphylococcal species, colonizing the human nares. Human-associated microbiomes such as the lung or gut have been repeatedly described as sides of phage-mediated HGT. However, it remains elusive how and to what degree the nasal microbiome is influencing the phage-mediated HGT of S. aureus. To address this question, we assembled a comprehensive collection of nasal bacterial isolates (comprising more than 30 Species and 300 isolates from 11 different human donors). Furthermore we determined their genetic composition via whole genome sequencing. When we probed the prophage content of 40 different nasal staphylococci, we observed that staphylococci harbour a sizable set of diverse prophages. Furthermore, prophages residing in the same ecological niche share significantly more similar prophages than staphylococci from different human donors. This is strong evidence that the human nares serve as location for phage-mediated HGT with strong implications for staphylococcal evolution and virulence. Given these results we propose to study the extent and influence of the nasal microbiome on phage-mediated HGT in all its aspects, phage induction, phage-host interaction and, eventually gene transfer by using a comprehensive set of computational and molecular biology approaches.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2330: New concepts in prokaryotic virus-host interactions - from single cells to microbial communities
• Co-Investigator: Professor Dr. Simon Heilbronner