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Genetic and Functional Insights Into the Mechanism That Controls Colony Morphology, Virulence, and Antibiotic Resistance in Mycobacterium avium.
Genetic and Functional Insights Into the Mechanism That Controls Colony Morphology, Virulence, and Antibiotic Resistance in Mycobacterium avium.
상세정보
- 자료유형
- 학위논문(국외)
- 기본표목-개인명
- 표제와 책임표시사항
- Genetic and Functional Insights Into the Mechanism That Controls Colony Morphology, Virulence, and Antibiotic Resistance in Mycobacterium avium.
- 발행, 배포, 간사 사항
- 발행, 배포, 간사 사항
- 형태사항
- 81 p.
- 일반주기
- Source: Dissertations Abstracts International, Volume: 87-04, Section: B.
- 일반주기
- Advisor: Cox, Jeffery S.;Stanley, Sarah A.
- 학위논문주기
- Thesis (Ph.D.)--University of California, Berkeley, 2025.
- 요약 등 주기
- 요약Nontuberculous mycobacteria (NTMs) represent over 170 different species of bacteria that are both genetically and phenotypically diverse. Although NTMs predominantly exist within the environment, the rates at which NTMs can serve as opportunistic pathogens within humans and animals is on the rise. The most prevalent NTM that causes disease in humans is Mycobacterium avium subspecies hominissuis (Mah). Mah is commonly found in premise plumbing sources like showerheads, and it is hypothesized that susceptible humans acquire Mah after inhalation of contaminated water droplets from these environmental reservoirs. Once Mah establishes infection within a susceptible host, it is extremely difficult to treat with antibiotics, with treatment failure and relapse occurring often. To date, few bacterial factors have been directly correlated with virulence within a host, and little is known about the mechanisms of inherent antibiotic resistance of Mah. As such, Mah is an emerging pathogen and research into its biology is essential to the development of more effective treatments.Mah switches reversibly between two distinct colony morphologies, smooth transparent (SmT) and smooth opaque (SmO). SmT cells are virulent and have high resistance to antibiotics while SmO cells are avirulent, antibiotic-sensitive and grow faster than SmT cells in culture. What causes colony morphology switching is an open question in the field, and understanding the mechanism of switching will enable identification of bacterial factors that are required for pathogenesis. Here we discover that a reversible transposition event governs the switch between the SmT and the SmO morphology by regulating expression of a periplasmic lipoprotein, Erp (extracellular repetitive protein). We also identified a mutation in a periplasmic protease, MarP, that locks Mah in the SmO state and blocks erp-mediated switching to SmT. Loss of function of either erp or marP decreases virulence and sensitizes Mah to a variety of different antibiotics. Our results indicate that Erp and MarP control colony morphology and their related phenotypic states by functioning in a signal transduction pathway that regulates a broad transcriptional response to periplasmic stress. Moreover, identification of components that control Mah colony morphology switching has revealed a potential new strategy for combating the inherent antibiotic resistance of M. avium infections.
- 주제명부출표목-일반주제명
- 주제명부출표목-일반주제명
- 주제명부출표목-일반주제명
- 주제명부출표목-일반주제명
- 주제명부출표목-일반주제명
- 비통제 색인어
- 비통제 색인어
- 비통제 색인어
- 비통제 색인어
- 부출표목-단체명
- 기본자료저록
- Dissertations Abstracts International. 87-04B.
- 전자적 위치 및 접속
- 원문정보보기
MARC
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■1001 ▼aNilsson, Hannah Joy.
■24510▼aGenetic and Functional Insights Into the Mechanism That Controls Colony Morphology, Virulence, and Antibiotic Resistance in Mycobacterium avium.
■260 ▼a[S.l.]▼bUniversity of California, Berkeley. ▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a81 p.
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-04, Section: B.
■500 ▼aAdvisor: Cox, Jeffery S.;Stanley, Sarah A.
■5021 ▼aThesis (Ph.D.)--University of California, Berkeley, 2025.
■520 ▼aNontuberculous mycobacteria (NTMs) represent over 170 different species of bacteria that are both genetically and phenotypically diverse. Although NTMs predominantly exist within the environment, the rates at which NTMs can serve as opportunistic pathogens within humans and animals is on the rise. The most prevalent NTM that causes disease in humans is Mycobacterium avium subspecies hominissuis (Mah). Mah is commonly found in premise plumbing sources like showerheads, and it is hypothesized that susceptible humans acquire Mah after inhalation of contaminated water droplets from these environmental reservoirs. Once Mah establishes infection within a susceptible host, it is extremely difficult to treat with antibiotics, with treatment failure and relapse occurring often. To date, few bacterial factors have been directly correlated with virulence within a host, and little is known about the mechanisms of inherent antibiotic resistance of Mah. As such, Mah is an emerging pathogen and research into its biology is essential to the development of more effective treatments.Mah switches reversibly between two distinct colony morphologies, smooth transparent (SmT) and smooth opaque (SmO). SmT cells are virulent and have high resistance to antibiotics while SmO cells are avirulent, antibiotic-sensitive and grow faster than SmT cells in culture. What causes colony morphology switching is an open question in the field, and understanding the mechanism of switching will enable identification of bacterial factors that are required for pathogenesis. Here we discover that a reversible transposition event governs the switch between the SmT and the SmO morphology by regulating expression of a periplasmic lipoprotein, Erp (extracellular repetitive protein). We also identified a mutation in a periplasmic protease, MarP, that locks Mah in the SmO state and blocks erp-mediated switching to SmT. Loss of function of either erp or marP decreases virulence and sensitizes Mah to a variety of different antibiotics. Our results indicate that Erp and MarP control colony morphology and their related phenotypic states by functioning in a signal transduction pathway that regulates a broad transcriptional response to periplasmic stress. Moreover, identification of components that control Mah colony morphology switching has revealed a potential new strategy for combating the inherent antibiotic resistance of M. avium infections.
■590 ▼aSchool code: 0028.
■650 4▼aMolecular biology.
■650 4▼aMicrobiology.
■650 4▼aGenetics.
■650 4▼aCellular biology.
■650 4▼aPathology.
■653 ▼aNontuberculous mycobacteria
■653 ▼aMycobacterium avium
■653 ▼aPathogens
■653 ▼aPeriplasmic stress
■690 ▼a0307
■690 ▼a0410
■690 ▼a0369
■690 ▼a0379
■690 ▼a0571
■71020▼aUniversity of California, Berkeley▼bMolecular & Cell Biology.
■7730 ▼tDissertations Abstracts International▼g87-04B.
■790 ▼a0028
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17359320▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
