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Identification and Functional Characterization of a Polyketide Synthase Gene Cluster in Lactobacillus reuteri R2lc
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Identification and Functional Characterization of a Polyketide Synthase Gene Cluster in Lactobacillus reuteri R2lc. |
| 개인저자 | Ozcam, Mustafa. |
| 단체저자명 | The University of Wisconsin - Madison. Food Science. |
| 발행사항 | [S.l.]: The University of Wisconsin - Madison., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 198 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-04B. Dissertation Abstract International |
| ISBN | 9781687973191 |
| 학위논문주기 | Thesis (Ph.D.)--The University of Wisconsin - Madison, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Advisor: van Pijkeren, Jan Peter. |
| 이용제한사항 | This item must not be sold to any third party vendors.This item must not be added to any third party search indexes. |
| 요약 | The bacterial gut symbiont species Lactobacillus reuteri inhabits the gastrointestinal tracts of many vertebrates including human, rat, mouse, pig and chicken, and numerous studies have showed that L. reuteri strains including R2lc modulate the host immune system. However, molecular mechanisms that contribute to the ability of some L. reuteri strains to thrive in the gut and modulate the host immune system are mostly unknown. Previously, it was shown that L. reuteri activates the aryl-hydrocarbon receptor (AhR)-a ligand-activated transcription factor that plays an important role in the mucosal immune system-by production of tryptophan catabolites. In this dissertation, we identified a novel pathway by which L. reuteri activates AhR, which is independent of tryptophan metabolism. We screened a library of 36 L. reuteri strains, and determined that R2lc and 2010, strains with a pigmented phenotype, are potent AhR activators. By whole genome sequencing and comparative genomics, we identified genes unique to R2lc and 2010. Our analyses demonstrated that R2lc harbors two genetically distinct polyketide synthase (PKS) clusters, pksR2lc01 and pksR2lc02, each encoded by a multi-copy plasmid. We found that the pksR2lc02 is responsible for R2lc-mediated AhR activation and immune modulation. L. reuteri 2010 has a gene cluster homologous to pksR2lc02 with an identical gene organization, which is also responsible for AhR activation.Since some microbial secondary metabolites including polyketides have antimicrobial activity, we assessed the role of R2lc-PKS clusters in suppressing other gut symbionts. In previous germ-free mice, R2lc outcompeted L. reuteri 100-23 in a PKS dependent manner. Moreover, R2lc suppressed 80.4% (41 out of 51) of gut-symbiont L. reuteri strains and inhibited in vitro biofilm formation through PKS-mediated bactericidal effect. By comparative genome analyses, we identified that L. reuteri PKS-resistant strains encode a homologous acyltransferase gene that provides resistance to R2lc-PKS in previous germ-free mice. Peptidoglycan analyses by HPLC and in vivo experiments revealed a role for cell wall acetylation in microbial fitness and competition. Our data provide evidence that a secondary metabolite gene cluster in L. reuteri provides in vivo competitive advantage and can modulate the host immune system through AhR activation. |
| 일반주제명 | Food science. Microbiology. |
| 언어 | 영어 |
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