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Investigations of Bacteroides thetaiotaomicron Population Dynamics
Investigations of Bacteroides thetaiotaomicron Population Dynamics
Investigations of Bacteroides thetaiotaomicron Population Dynamics

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20250211151029
ISBN  
9798383421208
DDC  
576
저자명  
Zagieboylo, Anna P.
서명/저자  
Investigations of Bacteroides thetaiotaomicron Population Dynamics
발행사항  
[Sl] : Yale University, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
108 p
주기사항  
Source: Dissertations Abstracts International, Volume: 86-02, Section: B.
주기사항  
Advisor: Goodman, Andrew L.
학위논문주기  
Thesis (Ph.D.)--Yale University, 2024.
초록/해제  
요약The human intestine contains a large, complex, and dynamic community of microbes termed the microbiota, which is made up of hundreds of individual species populations. Certain community compositions are linked to health or disease in the human host, and substantial effort has been directed towards identifying methods of modulating the microbiota composition for therapeutic purposes. While many studies assess which species are present or fluctuate within the community, little is known about fluctuations within individual isogenic populations over time. These types of high-resolution changes could reasonably be expected to have profound impacts on a commensal's ability to colonize the gut and promote health in the host. In this dissertation we show that, indeed, isogenic populations of the prominent gut commensal Bacteroides thetaiotaomicron undergo differentiation - through induced phenotypic heterogeneity or via evolution that leads to meaningful genetic diversity - and this variation within the population is important for survival in the gut. First, B. thetaiotaomicron secretes two proteins, together designated BSAP-5, that are upregulated specifically in response to host signals and result in phenotypic heterogeneity within the population. Although BSAP-5 lacks antimicrobial activity in vitro and in simple colonization models, it is important for intraspecies competition in physiologically relevant host conditions, including cocolonization with related Bacteroides species and gut inflammation. Second, we show that isogenic populations of B. thetaiotaomicron evolve rapidly and that selective pressures in vitro and in vivo lead to the expansion of subpopulations carrying beneficial mutations. Together, these results reveal insights on how symbiotic microbes persist in a shifting microbiota and demonstrate the importance of investigating changes within isogenic commensal populations.
일반주제명  
Microbiology
키워드  
Microbes
키워드  
Microbiota
키워드  
Human intestines
기타저자  
Yale University Microbiology
기본자료저록  
Dissertations Abstracts International. 86-02B.
전자적 위치 및 접속  
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MARC

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■035    ▼a(MiAaPQ)AAI30997128
■040    ▼aMiAaPQ▼cMiAaPQ
■0820  ▼a576
■1001  ▼aZagieboylo,  Anna  P.
■24510▼aInvestigations  of  Bacteroides  thetaiotaomicron  Population  Dynamics
■260    ▼a[Sl]▼bYale  University▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a108  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  86-02,  Section:  B.
■500    ▼aAdvisor:  Goodman,  Andrew  L.
■5021  ▼aThesis  (Ph.D.)--Yale  University,  2024.
■520    ▼aThe  human  intestine  contains  a  large,  complex,  and  dynamic  community  of  microbes  termed  the  microbiota,  which  is  made  up  of  hundreds  of  individual  species  populations.  Certain  community  compositions  are  linked  to  health  or  disease  in  the  human  host,  and  substantial  effort  has  been  directed  towards  identifying  methods  of  modulating  the  microbiota  composition  for  therapeutic  purposes.  While  many  studies  assess  which  species  are  present  or  fluctuate  within  the  community,  little  is  known  about  fluctuations  within  individual  isogenic  populations  over  time.  These  types  of  high-resolution  changes  could  reasonably  be  expected  to  have  profound  impacts  on  a  commensal's  ability  to  colonize  the  gut  and  promote  health  in  the  host.  In  this  dissertation  we  show  that,  indeed,  isogenic  populations  of  the  prominent  gut  commensal  Bacteroides  thetaiotaomicron  undergo  differentiation  -  through  induced  phenotypic  heterogeneity  or  via  evolution  that  leads  to  meaningful  genetic  diversity  -  and  this  variation  within  the  population  is  important  for  survival  in  the  gut.  First,  B.  thetaiotaomicron  secretes  two  proteins,  together  designated  BSAP-5,  that  are  upregulated  specifically  in  response  to  host  signals  and  result  in  phenotypic  heterogeneity  within  the  population.  Although  BSAP-5  lacks  antimicrobial  activity  in  vitro  and  in  simple  colonization  models,  it  is  important  for  intraspecies  competition  in  physiologically  relevant  host  conditions,  including  cocolonization  with  related  Bacteroides  species  and  gut  inflammation.  Second,  we  show  that  isogenic  populations  of  B.  thetaiotaomicron  evolve  rapidly  and  that  selective  pressures  in  vitro  and  in  vivo  lead  to  the  expansion  of  subpopulations  carrying  beneficial  mutations.  Together,  these  results  reveal  insights  on  how  symbiotic  microbes  persist  in  a  shifting  microbiota  and  demonstrate  the  importance  of  investigating  changes  within  isogenic  commensal  populations.
■590    ▼aSchool  code:  0265.
■650  4▼aMicrobiology
■653    ▼aMicrobes
■653    ▼aMicrobiota
■653    ▼aHuman  intestines
■690    ▼a0410
■71020▼aYale  University▼bMicrobiology.
■7730  ▼tDissertations  Abstracts  International▼g86-02B.
■790    ▼a0265
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160493▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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