Détails de l'offre
- Type de poste: PhD/Doctorat
- Secteur : Public
- Localité : International
- Limite de candidature : 15/06/2022
- Profil de poste:
Recherche et innovation - Domaine(s) :
Microbiologie et Immunologie, Autre
Description
Offer description
Staphylococcus aureus is among the leading causes of nosocomial and community acquired infections due to the fast acquisition of antibiotic resistance. In nature, main factors contributing to the S. aureus population control are bacteriophages. Those, that are obligatorily lytic, can kill infected S. aureus cells. They are considered to be alternatives to antibiotics in the treatment of infections by antibiotic-resistant S. aureus strains.
The majority of therapeutic staphylococcal phages belong to the Kayvirus genus of Twortvirinae subfamily of Caudovirales. They have large genomes (127- 149 kb), can encode about 200 proteins, are able to lyse the majority of strains in clinical S. aureus strain collections and can destruct staphylococcal biofilms.
Despite the great interest in these phages the functions of only less than half of their genes are known. It is also unclear what are the mechanisms underlying differences in strain specificity of particular kayviruses including the ability to overcome the restriction-modification systems of certain hosts.
Elucidation of these mechanisms is crucial for the progress in the construction of genetically modified kayviruses of desired host specificity and for the development of anti-staphylococcal phage therapies. Results of initial studies suggest that differences in the strain specificity of particular kayviruses may be correlated with the presence/absence of certain accessory genes in their genomes.
The aim of this project is to functionally analyse accessory and potential antirestriction genes of an especially wide strain-range kayvirus using the reverse genetic approach.
Genes for studies have been selected based on comparative analysis of various kayviruses genomes and specificity, and on in silico preliminary analysis of predicted kayviral proteins.
Their functions will be studied by the phenotypic analysis of phage mutants depleted of these genes and constructed in the project as well as by the phenotypic analysis of S. aureus cells carrying the selected genes cloned in a plasmid.
The contribution of particular genes to the kayvirus strain specificity determination and to the kayvirus therapeutic efficacy will be studied with the use of diversified S. aureus strain collection.
Comparative genomic analysis of pairs of related S. aureus strains representing isolates sensitive and resistant to particular kayviruses will be used to identify S. aureus determinants of susceptibility to these phages. Methodology will include basic microbiological and molecular biology techniques, gene cloning and expression, genomic, transcriptomic and proteomic analysis, site-directed mutagenesis, CRISPR-Cas-mediated selection of desired mutants, comparative genomic studies.
The studies will be financed from the National Science Centre OPUS project entitled “Functional genomic analysis of Staphylococcus aureus Kayvirus genus phages in a search for molecular basis of wide host-range and the strategies of survival with a host population”. A part of studies will be implemented in collaboration with foreign laboratories.