Defining the Role of Host Mitochondrial Dynamics in Rickettsial Pathogenicity

Abstract/Description/Artist Statement

Rickettsia is a genus of obligate intracellular bacteria, relying on establishing an intracellular niche within its host. Several species cause tick-borne diseases in humans, including spotted fever group rickettsioses such as Rocky Mountain spotted fever, which can range from mild febrile illness to severe, life-threatening systemic disease. Recent studies by our group and others have shown that pathogenic Rickettsia can use human THP-1 macrophages as a niche, likely avoiding host immune responses while simultaneously successfully replicating in these phagocytic cells. The degree of pathogenicity for each rickettsial species plays an important role in the ability of maintaining an intracellular niche in THP-1 macrophages, with mildly pathogenic species like Rickettsia parkeri and R. massiliae having greater success than non-pathogenic species like R. montanensis, which are eliminated by the host. The exact mechanisms by which pathogenic Rickettsia establish and maintain this intracellular niche in THP-1 macrophages are unknown, with modification of the host mitochondria presenting itself as a promising avenue to explore. This study aims to assess how the pathogenicity of Rickettsia impacts host mitochondrial dynamics. Using R. parkeri, R. massiliae, and R. montanensis, the degree of pathogenicity can be compared to the level of host mitochondrial manipulation, assessed by immunofluorescence and analysis of mitochondrial fusion and fission proteins  (MFN1/MFN2, DRP1, OPA-1). Results from this study will inform if manipulation of host mitochondria is important to Rickettsia pathogenicity, if not necessary for proliferation within THP-1 macrophages.

Presenting Author Name/s

Mark Ciardiello, Isaura Simoes

Faculty Advisor/Mentor

Isaura Simoes

Faculty Advisor/Mentor Email

isimes@odu.edu

Faculty Advisor/Mentor Department

Biological Sciences

College/School Affiliation

College of Sciences

Student Level Group

Graduate/Professional

Presentation Type

Poster

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Defining the Role of Host Mitochondrial Dynamics in Rickettsial Pathogenicity

Rickettsia is a genus of obligate intracellular bacteria, relying on establishing an intracellular niche within its host. Several species cause tick-borne diseases in humans, including spotted fever group rickettsioses such as Rocky Mountain spotted fever, which can range from mild febrile illness to severe, life-threatening systemic disease. Recent studies by our group and others have shown that pathogenic Rickettsia can use human THP-1 macrophages as a niche, likely avoiding host immune responses while simultaneously successfully replicating in these phagocytic cells. The degree of pathogenicity for each rickettsial species plays an important role in the ability of maintaining an intracellular niche in THP-1 macrophages, with mildly pathogenic species like Rickettsia parkeri and R. massiliae having greater success than non-pathogenic species like R. montanensis, which are eliminated by the host. The exact mechanisms by which pathogenic Rickettsia establish and maintain this intracellular niche in THP-1 macrophages are unknown, with modification of the host mitochondria presenting itself as a promising avenue to explore. This study aims to assess how the pathogenicity of Rickettsia impacts host mitochondrial dynamics. Using R. parkeri, R. massiliae, and R. montanensis, the degree of pathogenicity can be compared to the level of host mitochondrial manipulation, assessed by immunofluorescence and analysis of mitochondrial fusion and fission proteins  (MFN1/MFN2, DRP1, OPA-1). Results from this study will inform if manipulation of host mitochondria is important to Rickettsia pathogenicity, if not necessary for proliferation within THP-1 macrophages.