Vis enkel innførsel

dc.contributor.advisorHanssen, Anne-Merethe
dc.contributor.authorBastakoti Belbase, Srijana
dc.date.accessioned2024-06-04T09:12:16Z
dc.date.available2024-06-04T09:12:16Z
dc.date.embargoEndDate2026-06-14
dc.date.issued2024-06-14
dc.description.abstractIndividuals colonized by <i>S. aureus</i>, face a higher risk of <i>S. aureus</i> infections compared to non-carriers, and some throat carriers are prone to recurrent colonization even after antibiotic treatment. While <i>S. aureus</i> nasal colonization is well-studied, there is limited information about throat colonization. Our research aims to address this knowledge gap by exploring <i>S. aureus</i> factors crucial for throat colonization. We mimicked colonization by using a tonsillar cell model and mimicked an infection setting by using macrophage and other host factors. We employed transcriptome analysis (RNA-sequencing) and differentially expressed genes (DEGs) to identify specific <i>S. aureus</i> virulence factors under different conditions and time durations. We demonstrated distinct gene expression patterns associated with <i>S. aureus</i> colonization of tonsillar cells alone and in co-culture with <i>S. anginosus</i>, as well as during adaptation to macrophages and other host factors. Functional enrichment analysis revealed that these genes are mainly involved in essential biological processes such as adhesion, iron-regulation, defense response, and amino acid biosynthesis and transport, crucial for <i>S. aureus</i> adherence and survival. Our results highlight significant differences in gene expression between <i>S. aureus</i> exposed to professional phagocytes and those exposed to host factors, allowing us to identify key virulence factors and metabolic changes in extracellular and intracellular <i>S. aureus</i>. Understanding the roles of specific bacterial factors is essential for improving treatment options beyond antibiotics. This study sheds light on the transcriptome of <i>S. aureus</i> during colonization and infection scenarios, thereby advancing our understanding of <i>S. aureus</i> adaptive strategies. Further investigation into the roles of the identified genes in the host immune response within the context of a throat commensal landscape could provide valuable insights for future research and therapeutic development.en_US
dc.description.abstractIndivider kolonisert med <i>S. aureus</i> har en høyere risiko for <i>S. aureus</i>-infeksjoner sammenlignet med ikke-bærere, og noen halsbærere er utsatt for gjentatt kolonisering selv etter antibiotikabehandling. Mens <i>S. aureus</i> nesekolonisering er godt studert, er det begrenset informasjon om halskolonisering. Vår forskning vil addressere denne kunnskapsmangelen ved å utforske <i>S. aureus</i>-faktorer som er viktig i halskolonisering. Vi har etterliknet kolonisering ved å bruke en tonsillær cellemodell, og etterliknet infeksjon, ved å bruke makrofager og andre vertsfaktorer. Vi brukte transkriptomanalyse (RNA-sekvensar) for å identifisere spesifikke <i>S. aureus</i>-virulensfaktorer under forskjellige forhold og varighet. Vi fant spesifikke genekspresjonsmønster assosiert med <i>S. aureus</i>-kolonisering av tonsillære celler alene og i vekst sammen med <i>S. anginosus</i>, samt under tilpasning til makrofager og andre vertsfaktorer. Funksjonell enrichment analyse viste at disse genene hovedsakelig er involvert i essensielle biologiske prosesser som adhesjon, jernregulering, forsvarsrespons og aminosyrebiosyntese og transport, som er viktig for <i>S. aureus</i> adherens og overlevelse. Videre viste vår dataanalyse betydelige forskjeller i genuttrykk mellom <i>S. aureus</i> utsatt for profesjonelle fagocytter og de som er eksponert for vertsfaktorer, noe som lar oss identifisere nøkkelfaktorer og metabolske endringer i ekstracellulære og intracellulære <i>S. aureus</i>. Dette er viktig for å kunne forståspesifikke bakterielle faktorers rolle for å forbedre behandlingsalternativer utover antibiotika. Denne studien viser transkriptomet til <i>S. aureus</i> under koloniserings- og infeksjonsscenarier, og hjelper oss i å forstå dens adaptive strategier. Ytterligere undersøkelser av de identifiserte genene i møte med vertens immunrespons i et halsmikrobiom landskap kan gi verdifull innsikt for fremtidig forskning og terapeutisk utvikling.en_US
dc.description.doctoraltypeph.d.en_US
dc.description.popularabstractTrillions of bacteria inhabit our bodies, usually friendly but sometimes can turn against us and cause serious diseases. Staphylococcus aureus is one such bacterium, commonly present in the nose and throat but also able to cause infections like pneumonia and bloodstream infections. This study has shed light on the possible identification of tools (genes) used by S. aureus both for living in the human throat and during infection. This was mimicked in a laboratory setting, where we took a closer look at how S. aureus behaves at a genetic level when it meets and mingles with human cells and other bacteria living in the throat. We used an advanced technique revealing the bacterial gene signature. In this way, we have spotted S. aureus’ genes which are necessary for entering cells and for survival. By understanding the role of these genes, we might be able to find new ways to tackle S. aureus colonization and infections.en_US
dc.description.sponsorshipUiT the Arctic University of Norway (Recruitment position 3453) Odd Berg Group - Medical Research Fund Northern Norway Regional Health Authority Medical Research Programme project number HNF 1597-21 and HNF 1475-19 CANS grant to Einar Holsbøen_US
dc.identifier.urihttps://hdl.handle.net/10037/33710
dc.language.isoengen_US
dc.publisherUiT The Arctic University of Norwayen_US
dc.publisherUiT Norges arktiske universiteten_US
dc.relation.haspart<p>Paper I: Bastakoti, S., Ajayi, C., Julin, K., Johannessen, M. & Hanssen, A.M. (2023). Exploring differentially expressed genes of <i>Staphylococcus aureus</i> exposed to human tonsillar cells using RNA sequencing. <i>BMC Microbiology, 23</i>, 185. Also available in Munin at <a href=https://hdl.handle.net/10037/29754>https://hdl.handle.net/10037/29754</a>. <p>Paper II: Bastakoti, S., Pesonen, M., Ajayi, C., Julin, K., Corander, J., Johannessen, M. & Hanssen, A.M. (2024). Co-culturing with <i>Streptococcus anginosus</i> alters <i>Staphylococcus aureus</i> transcriptome when exposed to tonsillar cells. <i>Frontiers in Cellular and Infection Microbiology, 14</i>, 1326730. Also available in Munin at <a href=https://hdl.handle.net/10037/33709>https://hdl.handle.net/10037/33709</a>. <p>Paper III: Bastakoti, S., Ajayit, C., Ahatort, S.D., Johannessen, M., Lentz, C.S. & Hanssen, A.M. Transcriptomic responses of <i>Staphylococcus aureus</i> USA300 LAC during exposure to human Thpl macrophages and host factors. (Manuscript).en_US
dc.rights.accessRightsembargoedAccessen_US
dc.rights.holderCopyright 2024 The Author(s)
dc.subject.courseIDDOKTOR-003
dc.subjectStaphylococcus aureusen_US
dc.subjectCo-cultureen_US
dc.subjectTranscriptomicsen_US
dc.subjectColonizationen_US
dc.subjectInfectionen_US
dc.subjectAdaptationen_US
dc.subjectRNA-sequencingen_US
dc.subjectHosten_US
dc.titleExploring Staphylococcus aureus Adaptation in In vitro Colonization and Infection Models: A Transcriptomics Approachen_US
dc.typeDoctoral thesisen_US
dc.typeDoktorgradsavhandlingen_US


Tilhørende fil(er)

Thumbnail
Thumbnail
Thumbnail

Denne innførselen finnes i følgende samling(er)

Vis enkel innførsel