Bishnu Joshi

På grunn av koronautbruddet er auditoriet stengt for publikum. The auditorium will be closed to the public because of the corona outbreak. Prøveforelesning over oppgitt emne holdes kl. 10.15, samme sted: "The diagnostic and therapeutic use of extracellular vesicles” Prøveforelesningen vil også bli strømmet/the trail lecture will also be streamed . Avhandlingen er tilgjengelig her! The doctoral thesis! Disputasen vil i bli strømmet her. Opptak av disputasen vil være tilgjengelig i en måned. The defense will be streamed here. The recording will be available for one month.

De som ønsker å opponere ex auditorio kan sende e-post til leder av disputasen.
Opponents ex auditorio should sign up to leader of defense by e-mail to: ingebrigt.sylte@uit.no

Populærvitenskapelig sammendrag av avhandlingen:
Staphylococcus aureus and Enterococcus faecium are opportunistic pathogens that may cause diseases ranging from minor skin infection to severe blood stream infections.
The emergence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcal strains severely limits treatment options.
Bacteria release extracellular vesicles (EVs), defined as “particles naturally released from the cell that are delimited by a lipid bilayer and cannot replicate”. They are packaged with an array of virulence factors, resistant determinants, and nucleic acids and participate in host-microbe and microbe-microbe interactions.
EVs might be used for therapeutic applications e.g., carriers for drug delivery, vaccine, and diagnostic biomarkers. The characterization of EV cargo is limited in Gram-positive bacteria. Given the importance of EVs, this thesis aimed to examine proteome and transcriptome of these nanoparticles upon bacterial exposure to various growth conditions.
Using a label-free proteomic approach, E. faecium EVs proteome was profiled for the first time. We found that growth phase and growth conditions (e.g., media, sub-MIC dosage of vancomycin) influenced the proteome content. The EVs contained a wide range of different proteins including vaccine candidates, antimicrobial resistance determinants and virulence factors.
The sub-inhibitory dosage of vancomycin also influenced the proteome profile of MRSA and revealed relatively increased expression of EV- associated proteins that might be involved in bacterial colonization and antibiotic resistance (e.g., multiple antibiotic resistance regulators, amino acyltransferases, and penicillin binding proteins).
Intriguingly, we also demonstrated that EVs attenuated the susceptibility of MRSA to vancomycin, which is commonly used as first-line therapy in clinical practices. Transcriptomic analysis of RNA isolated from S. aureus-derived EVs revealed presence of various RNA biotypes including mRNA, rRNA, tRNA, and small RNA. In summary, the thesis demonstrate that several virulence factors, immunogenic proteins, and/or small RNAs were associated with the EVs isolated from E. faecium and S. aureus.

Hovedveileder
Professor Mona Johannessen, Institutt for medisinsk biologi, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet

 
Biveiledere
Professor II Kristin Hegstad, Institutt for medisinsk biologi, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet

Forsker Ph.D Fatemeh Askarian, Institutt for medisinsk biologi, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet

Bedømmelseskomité
Professor, Bart Devreese, University of Ghent– 1. opponent

Professor Hanne Winther-Larsen, Universitetet i Oslo-  2.opponent

Førsteamanuensis Jorunn Pauline Cavanagh, Institutt for klinisk medisin, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet – leder av komité

Disputasleder
Professor Ingebrigt Sylte, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet