Project Details
Projekt
Molecular cross-talk between Sa3int phages and their Stapylococcus aureus host
Applicant
Professorin Dr. Christiane Wolz
Subject Area
Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
Metabolism, Biochemistry and Genetics of Microorganisms
Metabolism, Biochemistry and Genetics of Microorganisms
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 464612409
As a major opportunistic pathogen of human and animals Staphylococcus aureus asymptomatically colonizes the nasal cavity, but is also a leading cause of life-threatening acute and chronic infections. Evolution of the species as a result of short- and long-term adaptation to diverse hosts is tightly linked to phage-mediated transfer of extra-chromosomal mobile elements as well as chromosomal markers. S. aureus strains can carry up to four temperate phages, many of which possess accessory genes coding for staphylococcal virulence factors. More than 90% of the human nasal isolates of S. aureus were found to carry Sa3int phages, which integrate as prophages into the bacterial hlb gene thus disrupting the expression of the sphingomyelinase Hlb, an important virulence factor under certain infection conditions. Among the virulence factors-encoding genes carried by the ϕSa3-phages are staphylokinase, enterotoxins, chemotaxis-inhibitory proteins, and/or staphylococcal complement inhibitors, all of which are highly human-specific and probably essential for bacterial survival in the human host. Thus, both insertion of the prophages into and excision from the bacterial genome have the potential to confer a fitness advantage to S. aureus. There is now also growing evidence that Sa3int phages might perform “active lysogeny”, a process during which a prophage is temporally excised from the chromosome without forming intact phage particles. However, how the S. aureus host modulates the life cycle of its temperate phages remains largely unknown. Our data suggest that the bacterial factors supposedly involved in the interaction of the bacterial host with its phages are likely to be strain specific, with certain S. aureus strains being more prone than others to support either a lysogenic or a lytic life cycle. We aim to decipher the molecular mechanisms regulating the transition of Sa3int phages from a lysogenic to “active lysogenic” or to the lytic phase. Bioinformatic analyses will give insights into the diversity of Sa3int phages and their linkage to certain S. aureus linages. Phage and bacterial factors involved in the lysogenic-“active lysogenic”-lytic switch will be elucidated and their putative interactions assessed. Lysogeny, “active lysogeny” and lytic phage cycles will be monitored over time on the single cell level using microfluidic devices. This will help us understand how these peculiar phages have evolved together with their bacterial host S. aureus.
DFG Programme
Priority Programmes
