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Metabolic Cross-Feeding Supports Growth of Candida albicans and Enterococcus faecalis in the Gut Microbiome
Metabolic Cross-Feeding Supports Growth of Candida albicans and Enterococcus faecalis in the Gut Microbiome
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211153030
- ISBN
- 9798346876977
- DDC
- 576
- 저자명
- Gause, Haley.
- 서명/저자
- Metabolic Cross-Feeding Supports Growth of Candida albicans and Enterococcus faecalis in the Gut Microbiome
- 발행사항
- [Sl] : University of California, San Francisco, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 83 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-06, Section: B.
- 주기사항
- Advisor: Gross, Carol.
- 학위논문주기
- Thesis (Ph.D.)--University of California, San Francisco, 2024.
- 초록/해제
- 요약The adult gut microbiome is a diverse community of thousands of microorganisms spanning all three kingdoms of life. In contrast, the infant gut microbiome is relatively simple, offering a powerful, biologically relevant system to study foundational microbial community interactions. The fungal species Candida albicans and the bacterium Enterococcus faecalis are both common members of the infant gut microbiome, with co-occurrence of these two species widely reported across various dysbiotic gut environments. While previous studies suggest that C. albicans and E. faecalis interact in the gut, the mechanisms behind these interactions remain unclear. To more deeply probe the interaction between C. albicans and E. faecalis in the gut, we used dual RNA-sequencing to profile the transcriptional responses of both organisms during co-culture and compared them to individual growth under two conditions: (1) an in vitro condition designed to mimic certain aspects of the gut environment and (2) the germ-free mouse gut. Gene expression analysis of revealed that both species strongly upregulate citrate-related genes in each other's presence: C. albicans upregulates CIT1 (citrate synthase) which produces citrate, while E. faecalis upregulates the entire cit operon, responsible for citrate metabolism. In in vitro co-cultures, we show that citrate is produced and secreted from C. albicans and consumed by E. faecalis, revealing a cross-feeding interaction. We further show that this citrate cross-feeding supports increased growth of E. faecalis, which depends on both C. albicans' expression of CIT1 and E. faecalis' expression of the cit operon. Formate, a Short Chain Fatty Acid (SCFA) known to be toxic to fungi, is a byproduct of citrate metabolism in E. faecalis. Indeed, we observed higher formate secretion from E. faecalis strains capable of metabolizing citrate. Our RNA profiling revealed that C. albicans strongly upregulates three formate dehydrogenases (FDHs) when co- cultured with E. faecalis. These FDHs detoxify formate and we show that their expression provides C. albicans with a growth advantage in the presence of formate. These findings reveal a metabolically driven interaction between C. albicans and E. faecalis in the gut, where cross-feeding of citrate and detoxification of formate facilitates the growth of both species when they are cultured together. Using a simplified fungal-bacterial co-culture system, our studies begin to reveal the mechanistic complexities of metabolic sharing between a eukaryote and a bacterium.
- 일반주제명
- Microbiology
- 일반주제명
- Molecular biology
- 일반주제명
- Biochemistry
- 키워드
- Microbiome
- 키워드
- Candida albicans
- 키워드
- Microorganism
- 기타저자
- University of California, San Francisco Biochemistry and Molecular Biology
- 기본자료저록
- Dissertations Abstracts International. 86-06B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798346876977
■035 ▼a(MiAaPQ)AAI31635454
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a576
■1001 ▼aGause, Haley.▼0(orcid)0000-0001-9738-6808
■24510▼aMetabolic Cross-Feeding Supports Growth of Candida albicans and Enterococcus faecalis in the Gut Microbiome
■260 ▼a[Sl]▼bUniversity of California, San Francisco▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a83 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-06, Section: B.
■500 ▼aAdvisor: Gross, Carol.
■5021 ▼aThesis (Ph.D.)--University of California, San Francisco, 2024.
■520 ▼aThe adult gut microbiome is a diverse community of thousands of microorganisms spanning all three kingdoms of life. In contrast, the infant gut microbiome is relatively simple, offering a powerful, biologically relevant system to study foundational microbial community interactions. The fungal species Candida albicans and the bacterium Enterococcus faecalis are both common members of the infant gut microbiome, with co-occurrence of these two species widely reported across various dysbiotic gut environments. While previous studies suggest that C. albicans and E. faecalis interact in the gut, the mechanisms behind these interactions remain unclear. To more deeply probe the interaction between C. albicans and E. faecalis in the gut, we used dual RNA-sequencing to profile the transcriptional responses of both organisms during co-culture and compared them to individual growth under two conditions: (1) an in vitro condition designed to mimic certain aspects of the gut environment and (2) the germ-free mouse gut. Gene expression analysis of revealed that both species strongly upregulate citrate-related genes in each other's presence: C. albicans upregulates CIT1 (citrate synthase) which produces citrate, while E. faecalis upregulates the entire cit operon, responsible for citrate metabolism. In in vitro co-cultures, we show that citrate is produced and secreted from C. albicans and consumed by E. faecalis, revealing a cross-feeding interaction. We further show that this citrate cross-feeding supports increased growth of E. faecalis, which depends on both C. albicans' expression of CIT1 and E. faecalis' expression of the cit operon. Formate, a Short Chain Fatty Acid (SCFA) known to be toxic to fungi, is a byproduct of citrate metabolism in E. faecalis. Indeed, we observed higher formate secretion from E. faecalis strains capable of metabolizing citrate. Our RNA profiling revealed that C. albicans strongly upregulates three formate dehydrogenases (FDHs) when co- cultured with E. faecalis. These FDHs detoxify formate and we show that their expression provides C. albicans with a growth advantage in the presence of formate. These findings reveal a metabolically driven interaction between C. albicans and E. faecalis in the gut, where cross-feeding of citrate and detoxification of formate facilitates the growth of both species when they are cultured together. Using a simplified fungal-bacterial co-culture system, our studies begin to reveal the mechanistic complexities of metabolic sharing between a eukaryote and a bacterium.
■590 ▼aSchool code: 0034.
■650 4▼aMicrobiology
■650 4▼aMolecular biology
■650 4▼aBiochemistry
■653 ▼aInterspecies interactions
■653 ▼aMicrobiome
■653 ▼aEnterococcus faecalis
■653 ▼aCandida albicans
■653 ▼aMicroorganism
■690 ▼a0410
■690 ▼a0307
■690 ▼a0487
■71020▼aUniversity of California, San Francisco▼bBiochemistry and Molecular Biology.
■7730 ▼tDissertations Abstracts International▼g86-06B.
■790 ▼a0034
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17164674▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
