Investigating the regulation of virulence by Sae in Staphylococcus aureus

dc.contributor.advisorChairperson, Graduate Committee: Jovanka Voyich-Kaneen
dc.contributor.authorCollins, Madison Paige Martinen
dc.contributor.otherRanjan K. Behera, Kyler B. Pallister, Tyler J. Evans, Owen Burroughs, Caralyn Flack, Fermin E. Guerra, Willis Pullman, Brock Cone, Jennifer G. Dankoff, Tyler K. Nygaard, Shaun R. Brinsmade and Jovanka M. Voyich were co-authors of the article, 'The accessory gene saeP of the saeR/S two-component gene regulatory system impacts Staphylococcus aureus virulence during neutrophil interaction' in the journal 'Frontiers in microbiology' which is contained within this dissertation.en
dc.contributor.otherKyler Pallister and Jovanka M. Voyich were co-authors of the article, 'Differential analysis of host/pathogen RNA expression via next generation sequencing reveals Staphylococcus aureus utilizes saeR/S-mediated factors to inhibit human neutrophil functions following phagocytosis' which is contained within this dissertation.en
dc.date.accessioned2022-05-13T16:31:53Z
dc.date.available2022-05-13T16:31:53Z
dc.date.issued2020en
dc.description.abstractStaphylococcus aureus (S. aureus) is a common commensal bacterium known to colonize, at minimum, 30% of the human population. It is also capable of causing a range of diseases that span from minor skin- and soft-tissue infections to life-threatening diseases. The diversity of S. aureus infections is due to the ability of the bacteria to sense and respond to environmental change. Virulence regulation in S. aureus can be attributed to the use of two-component gene regulatory systems (TCS). TCS can sense a variety of encounters including: antibiotics, heat stress, or immune cell encounter. Neutrophils are a key leukocyte involved in bacterial clearance in the human host. It follows that S. aureus has evolved mechanisms to sense and respond to neutrophils. The Sae TCS, is immediately up-regulated after neutrophil phagocytosis and has been demonstrated to be critical in the success of S. aureus both in vitro and in vivo. SaeS, the histidine kinase, and the respective response regulator, SaeR, are established components of the Sae TCS and their importance during neutrophil evasion and pathogenesis is well established. However, little is known about two accessory genes, saeP and saeQ. Results described herein using human neutrophil and murine models of infection provide evidence that SaeP modulates the Sae-mediated response of S. aureus against human neutrophils and suggest that saeQ and saeP together impact pathogenesis in vivo. To identify additional host and pathogen factors important during neutrophil interaction, we used differential analysis of host/pathogen RNA expression via Next Generation Sequencing to define the influence of SaeR/S on the host-pathogen transcriptome following neutrophil phagocytosis. Results determined that in the early stages of S. aureus infection, SaeR/S-dependent factors significantly modulate neutrophil processes involved in several pathways including autophagy, TNF-alpha signaling, and NF-kappaB signaling. These results suggest S. aureus uses SaeR/S-regulated virulence factors to hijack human neutrophil function at the transcriptional level to inhibit proper killing by neutrophils and allow for S. aureus persistence within the host.en
dc.identifier.urihttps://scholarworks.montana.edu/handle/1/16733en
dc.language.isoenen
dc.publisherMontana State University - Bozeman, College of Agricultureen
dc.rights.holderCopyright 2020 by Madison Paige Martin Collinsen
dc.subject.lcshStaphylococcus aureusen
dc.subject.lcshGenetic regulationen
dc.subject.lcshNeutrophilsen
dc.subject.lcshRNAen
dc.subject.lcshMicrobial geneticsen
dc.subject.lcshHost-parasite relationshipsen
dc.titleInvestigating the regulation of virulence by Sae in Staphylococcus aureusen
dc.typeDissertationen
mus.data.thumbpage101en
thesis.degree.committeemembersMembers, Graduate Committee: Diane Bimczok; Mark T. Quinn; Michelle Flennikenen
thesis.degree.departmentMicrobiology & Cell Biology.en
thesis.degree.genreDissertationen
thesis.degree.namePhDen
thesis.format.extentfirstpage1en
thesis.format.extentlastpage130en

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