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Functional Characterization of the Shigella spp. Effector OspB
Functional Characterization of the Shigella spp. Effector OspB
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202105145
- ISBN
- 9798265410016
- DDC
- 576
- 서명/저자
- Functional Characterization of the Shigella spp. Effector OspB
- 발행사항
- [Sl] : Harvard University, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 247 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-05, Section: B.
- 주기사항
- Advisor: Goldberg, Marcia B.
- 학위논문주기
- Thesis (Ph.D.)--Harvard University, 2025.
- 초록/해제
- 요약Shigella flexneri is an intracellular bacterial pathogen that uses a Type 3 Secretion System (T3SS) to deliver effector proteins into host epithelial cells, enabling invasion, replication, and intercellular spread. Among these effectors, OspB is a conserved but poorly understood protein previously linked to host cell proliferation. In this work, we sought to fill this gap, defining OspB as a cysteine protease, characterizing its substrate recognition motif, and investigating its function during infection.Transcriptomic profiling reveals that OspB alters host gene expression during infection, but not during ectopic expression, suggesting that its activity is dependent on infection-specific conditions. We found that during S. flexneri infection, OspB upregulates pathways related to vesicle trafficking, chromatin remodeling, and cell proliferation, highlighting its potential to reshape the host cellular environment. Using a combination of motif prediction and N-terminomics mass spectrometry, we identify CHMP2B, a core component of the ESCRT-III membrane repair complex, as a substrate of OspB. We show using functional assays that OspB cleaves CHMP2B in transfected cells and enhances membrane repair during infection. Moreover, ESCRT-III components, including CHMP2B and VPS4, localize to actin tails at sites of Shigella cell-to-cell spread, suggesting that this machinery plays an active role in resolving membrane stress during bacterial dissemination.Taken together, this work establishes host membrane repair - specifically ESCRT-mediated repair - as an important and previously unappreciated target of Shigella manipulation during epithelial cell infection. OspB enhances this process through its protease activity, revealing a novel consequence of OspB during Shigella infection.
- 일반주제명
- Microbiology
- 일반주제명
- Public health
- 일반주제명
- Cellular biology
- 일반주제명
- Pathology
- 키워드
- Epithelial cell
- 기타저자
- Harvard University Biological Sciences in Public Health
- 기본자료저록
- Dissertations Abstracts International. 87-05B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■006m o d
■007cr#unu||||||||
■020 ▼a9798265410016
■035 ▼a(MiAaPQ)AAI32241067
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a576
■1001 ▼aWestervelt, Kathleen Amanda.
■24510▼aFunctional Characterization of the Shigella spp. Effector OspB
■260 ▼a[Sl]▼bHarvard University▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a247 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-05, Section: B.
■500 ▼aAdvisor: Goldberg, Marcia B.
■5021 ▼aThesis (Ph.D.)--Harvard University, 2025.
■520 ▼aShigella flexneri is an intracellular bacterial pathogen that uses a Type 3 Secretion System (T3SS) to deliver effector proteins into host epithelial cells, enabling invasion, replication, and intercellular spread. Among these effectors, OspB is a conserved but poorly understood protein previously linked to host cell proliferation. In this work, we sought to fill this gap, defining OspB as a cysteine protease, characterizing its substrate recognition motif, and investigating its function during infection.Transcriptomic profiling reveals that OspB alters host gene expression during infection, but not during ectopic expression, suggesting that its activity is dependent on infection-specific conditions. We found that during S. flexneri infection, OspB upregulates pathways related to vesicle trafficking, chromatin remodeling, and cell proliferation, highlighting its potential to reshape the host cellular environment. Using a combination of motif prediction and N-terminomics mass spectrometry, we identify CHMP2B, a core component of the ESCRT-III membrane repair complex, as a substrate of OspB. We show using functional assays that OspB cleaves CHMP2B in transfected cells and enhances membrane repair during infection. Moreover, ESCRT-III components, including CHMP2B and VPS4, localize to actin tails at sites of Shigella cell-to-cell spread, suggesting that this machinery plays an active role in resolving membrane stress during bacterial dissemination.Taken together, this work establishes host membrane repair - specifically ESCRT-mediated repair - as an important and previously unappreciated target of Shigella manipulation during epithelial cell infection. OspB enhances this process through its protease activity, revealing a novel consequence of OspB during Shigella infection.
■590 ▼aSchool code: 0084.
■650 4▼aMicrobiology
■650 4▼aPublic health
■650 4▼aCellular biology
■650 4▼aPathology
■653 ▼aShigella flexneri
■653 ▼aType 3 Secretion System
■653 ▼aEpithelial cell
■653 ▼aEffector proteins
■690 ▼a0410
■690 ▼a0379
■690 ▼a0573
■690 ▼a0571
■71020▼aHarvard University▼bBiological Sciences in Public Health.
■7730 ▼tDissertations Abstracts International▼g87-05B.
■790 ▼a0084
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17359602▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
