Disputas - Martin Owczarek Korsner Christiansen

Avhandlingen

Auditoriet er åpent for publikum, men disputasen vil likevel bli strømmet her

Opptak av disputasen vil være tilgjengelig i et døgn

The auditorium is open to the public, but the defense will also be streamed here

A recording of the defense will be available for 24 hours

Prøveforelesning over oppgitt emne holdes kl. 10:15, samme sted:

“Coagulase-negative staphylococcus genomics – from commensals to pathogens”

Prøveforelesningen vil også bli strømmet/the trial lecture will also be streamed

Populærvitenskapelig sammendrag av avhandlingen

Over the past decades, major advances in medicine have dramatically improved survival rates for both premature infants and children with cancer. However, the intensive treatments required to save these patients often leave them with weakened immune systems for prolonged periods. Many also depend on central venous catheters and repeated courses of antibiotics, increasing their risk of developing serious infections caused by antibiotic-resistant bacteria.

Among the bacterial groups that have become increasingly important in hospital settings are coagulase-negative staphylococci (CoNS). Although these bacteria are a normal part of the healthy skin microbiota, they can cause severe bloodstream infections when they gain access to the circulation, particularly in immunocompromised patients. They readily adhere to catheters and other medical devices where they form biofilms, a protective layer that shields the bacteria from both the immune system and antibiotic treatment.

The main virulence factors in CoNs are biofilm formation, a key virulence trait that enable bacteria to evade host immune defenses and survive antibiotic therapy. In addition, bacterial capsules have been described as a virulence factor also shielding the bacteria from recognition from the immune defense. The bacterial capsule has not been thoroughly described for S.haemolyticus.

In this thesis, we explored whether combinations of established antibiotics, including cefazolin and gentamicin, could improve treatment of resistant CoNS isolates.

Further we compared the role of the serine-rich repeat surface protein SraP and different capsule types in adhesion, biofilm formation and adhesion. To investigate how SraP and the capsule affect the interplay with the immune system, we used an ex vivo human whole-blood model that allowed us to measure key aspects of the immune response, including cytokine release and complement activation.

Building on the identification of novel capsule types previously discovered by our research group, we showed that isolates with different capsule types varied markedly in their ability to form biofilms, with some capsule types producing substantially more biofilm than others, whereas the capsule appeared to play a smaller role than expected in protecting S. haemolyticus against the host immune response. We further demonstrated that SraP contributes to the bacterium's ability to adhere to host cells. Together, these findings provide new insights into the characteristics that distinguish disease-causing strains from harmless skin bacteria and improve our understanding of how S. haemolyticus causes infection.

In the longer term, this knowledge may contribute to the development of more targeted therapeutic strategies and novel alternatives to conventional antibiotics. Such advances are particularly important at a time when antimicrobial resistance represents one of the greatest challenges facing modern medicine, and when the most vulnerable patient populations require treatments that are both more effective and less harmful.

Hovedveileder

Professor Jorunn Pauline Cavanagh, IKM, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet

Biveileder

Førsteamanuensis Hildegunn Norbakken Granslo, IKM
Forsker Hermoine Jean Venter, IFA
Professor Claus Andreas Klingenberg, IKM
Fatemeh Askarian, University of California San Diego

Bedømmelseskomité

Professor Linus Sandegren, Uppsala University– 1. opponent

Senior Scientist Malcolm Horsburgh, University of Liverpool- 2. opponent

Professor Johanna U Ericson, Institutt for medisinsk biologi, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet – leder av komité

Disputasleder

Professor Inigo Zubiavrre Martinez, Institutt for klinisk medisin, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet