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Identifying and Characterizing Genetic Determinants of Antibiotic Sensitivity in Mycobacterium abscessus- [electronic resource]
Identifying and Characterizing Genetic Determinants of Antibiotic Sensitivity in Mycobacterium abscessus- [electronic resource]
상세정보
- 자료유형
- 학위논문(국외)
- 자관 청구기호
- 기본표목-개인명
- 표제와 책임표시사항
- Identifying and Characterizing Genetic Determinants of Antibiotic Sensitivity in Mycobacterium abscessus - [electronic resource] / Ronald Rodriguez
- 발행, 배포, 간사 사항
- 발행, 배포, 간사 사항
- 형태사항
- 1 online resource(p.92 )
- 일반주기
- Source: Dissertations Abstracts International, Volume: 85-04, Section: B.
- 일반주기
- Advisor: Stanley, Sarah.
- 학위논문주기
- Thesis (Ph.D.)--University of California, Berkeley, 2022.
- 이용제한주기
- This item must not be sold to any third party vendors.
- 요약 등 주기
- 요약The work presented here focuses on identifying and characterizing genetic determinants of antibiotic sensitivity in Mycobacterium abscessus (Mabs), a non-tuberculosis mycobacterial pathogen responsible for various human infections that are notoriously difficult to treat with standard antibacterial therapy in clinical settings. Using bacterial genetics and high-throughput DNA sequencing methods, we have identified genes important for growth on amikacin and clarithromycin, two clinically relevant antibiotics used to treat Mabs, and ethionamide (ETH), a second-line drug currently used for treating multidrug-resistant tuberculosis infections. In chapters 1 and 2, I discuss the types of infections caused by Mabs, notable risk factors associated with Mabs infections, its epidemiology and transmission, and treatment options currently available. In chapter 3, I specifically focus on antibiotic treatment of Mabs infections and provide an overview on various antibiotic resistance mechanisms that are associated with treatment failure. In chapter 4, I present data that examines the antibacterial activity of ETH alone and in combination with clinically relevant antibiotics in vitro and in vivo. Furthermore, we present sequencing data on MAB_2648c, which encodes for a transcriptional repressor that confers ETH resistance. We demonstrate that Mab_2648c-dependent ETH resistance requires the activity of MmpSL5, a putative membrane transporter whose function remains unknown. In chapter 5, we attempt to identify the function of MmpSL5 and its potential substrates. In conclusion, we show that ETH is slightly bactericidal against Mabs in vitro and potentially in vivo, does not antagonize with clinically relevant antibiotics used to treat Mabs infections, and identified a biological mechanism that confers ETH resistance in Mabs. Future work should further examine the repurposing potential of ETH against Mabs and identify compounds that may reverse ETH resistance in vitro and in vivo.
- 주제명부출표목-일반주제명
- 주제명부출표목-일반주제명
- 주제명부출표목-일반주제명
- 주제명부출표목-일반주제명
- 주제명부출표목-일반주제명
- 비통제 색인어
- 비통제 색인어
- 비통제 색인어
- 비통제 색인어
- 비통제 색인어
- 부출표목-단체명
- 기본자료저록
- Dissertations Abstracts International. 85-04B.
- 기본자료저록
- Dissertation Abstract International
- 전자적 위치 및 접속
- 원문정보보기
- 소장사항
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202402 2024
MARC
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■006m o d
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■035 ▼a(MiAaPQ)AAI30244277
■040 ▼aMiAaPQ▼cMiAaPQ
■08204▼a576
■090 ▼a전자도서(박사논문)
■1001 ▼aRodriguez, Ronald.
■24510▼aIdentifying and Characterizing Genetic Determinants of Antibiotic Sensitivity in Mycobacterium abscessus▼h[electronic resource]▼cRonald Rodriguez
■260 ▼a[S.l.]▼bUniversity of California, Berkeley. ▼c2022
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2022
■300 ▼a1 online resource(p.92 )
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-04, Section: B.
■500 ▼aAdvisor: Stanley, Sarah.
■5021 ▼aThesis (Ph.D.)--University of California, Berkeley, 2022.
■506 ▼aThis item must not be sold to any third party vendors.
■520 ▼aThe work presented here focuses on identifying and characterizing genetic determinants of antibiotic sensitivity in Mycobacterium abscessus (Mabs), a non-tuberculosis mycobacterial pathogen responsible for various human infections that are notoriously difficult to treat with standard antibacterial therapy in clinical settings. Using bacterial genetics and high-throughput DNA sequencing methods, we have identified genes important for growth on amikacin and clarithromycin, two clinically relevant antibiotics used to treat Mabs, and ethionamide (ETH), a second-line drug currently used for treating multidrug-resistant tuberculosis infections. In chapters 1 and 2, I discuss the types of infections caused by Mabs, notable risk factors associated with Mabs infections, its epidemiology and transmission, and treatment options currently available. In chapter 3, I specifically focus on antibiotic treatment of Mabs infections and provide an overview on various antibiotic resistance mechanisms that are associated with treatment failure. In chapter 4, I present data that examines the antibacterial activity of ETH alone and in combination with clinically relevant antibiotics in vitro and in vivo. Furthermore, we present sequencing data on MAB_2648c, which encodes for a transcriptional repressor that confers ETH resistance. We demonstrate that Mab_2648c-dependent ETH resistance requires the activity of MmpSL5, a putative membrane transporter whose function remains unknown. In chapter 5, we attempt to identify the function of MmpSL5 and its potential substrates. In conclusion, we show that ETH is slightly bactericidal against Mabs in vitro and potentially in vivo, does not antagonize with clinically relevant antibiotics used to treat Mabs infections, and identified a biological mechanism that confers ETH resistance in Mabs. Future work should further examine the repurposing potential of ETH against Mabs and identify compounds that may reverse ETH resistance in vitro and in vivo.
■590 ▼aSchool code: 0028.
■650 4▼aMicrobiology.
■650 4▼aPublic health.
■650 4▼aPharmacology.
■650 4▼aEpidemiology.
■650 4▼aGenetics.
■653 ▼aMycobacterium abscessus
■653 ▼aMycobacterial pathogen
■653 ▼aTranscriptional repressor
■653 ▼aAntibiotics
■653 ▼aAntibiotic treatment
■690 ▼a0410
■690 ▼a0369
■690 ▼a0766
■690 ▼a0419
■690 ▼a0573
■71020▼aUniversity of California, Berkeley▼bMicrobiology.
■7730 ▼tDissertations Abstracts International▼g85-04B.
■773 ▼tDissertation Abstract International
■790 ▼a0028
■791 ▼aPh.D.
■792 ▼a2022
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T16931270▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
■980 ▼a202402▼f2024
