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The Bacterial Protein Targeted by the Class IIb Bacteriocin Plantaricin EF and the Potential of Plantaricin EF to Improve Metabolic Health
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | The Bacterial Protein Targeted by the Class IIb Bacteriocin Plantaricin EF and the Potential of Plantaricin EF to Improve Metabolic Health. |
| 개인저자 | Heeney, Dustin. |
| 단체저자명 | University of California, Davis. Microbiology. |
| 발행사항 | [S.l.]: University of California, Davis., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 172 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-06B. Dissertation Abstract International |
| ISBN | 9781392581049 |
| 학위논문주기 | Thesis (Ph.D.)--University of California, Davis, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-06, Section: B.
Advisor: Marco, Maria L. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | Consumption of high fat high sugar diets (HFD) results in obesity, a serious metabolic disorder with multiple pathological co-morbidities including diabetes, specific cancers, and non-alcoholic fatty liver disease. The gut microbiota are now known to contribute to the etiology and progression of this disease. Breakdown in the intestinal barrier results in increases in the systemic release of microbial-derived molecules (e.g. LPS) from the lumen into adipose tissue and other organs results in chronic inflammation and metabolic dysfunction. Conversely, certain members of the gut microbiota and probiotic bacteria, including members of the genus Lactobacillus, can be useful to counteract the effects of obesogenic diets and related pathologies (Chapter I, Heeney et al., 2018 Current Opinion in Biotechnology). In particular, Lactobacillus plantarum has repeatedly been associated with increased tight junction protein production in intestinal tissue and reductions in adipose and liver tissue inflammation in humans, even in the presence of diet-induced obesity (DIO). The precise molecular mechanisms by which L. plantarum and other bacteria alter intestinal and systemic physiology to promote barrier function have yet to be established. We hypothesized that Plantaricin EF (PlnEF), a two peptide bacteriocin produced exclusively by strains of L. plantarum, may act as an anti-obesogenic molecule through direct actions on the intestinal barrier. This hypothesis was explored by conducting a DIO prevention study (Chapter II, Heeney et al., 2018, Gut Microbes), where C57BL/6J mice were subjected to a HFD (43% kcal from fat) with or without oral administration of 109 cells of wildtype Lactobacillus plantarum NCIMB8826 (LP) or a mutant of LP with a deletion in the plnEFI operon (MU). Mice given LP, but not the MU strain, gained significantly less weight and ate less food than the HFD fed controls. These improved metabolic outcomes were strongly associated with decreased adipose tissue inflammation and increases in ileal tight junction protein ZO-1, an indication of improved barrier function. The potential for PlnEF to prevent barrier damage to human colon epithelial cells was shown using synthetic PlnEF peptides in a Caco-2 cell model challenged with inflammatory cytokines. To further investigate the mechanism by which PlnEF acts on host cells, the PlnEF receptor on sensitive bacterial cells was identified (Chapter III, Heeney et al., 2019, MicrobiologyOpen). With the application of a forward genetics approach using spontaneous resistant mutants of a PlnEF-sensitive strain (L. plantarum strain 965) CorC, a putative magnesium/cobalt efflux protein, was identified as the receptor for PlnEF. The necessity of CorC in conferring sensitivity to PlnEF was confirmed by expressing native and mutant LP965 CorC proteins in a PlnEF-resistant host and tests of metal sensitivity and ATP release. In the final chapter (IV), I attempted to identify direct benefits of PlnEF consumption by DIO mice with a novel microencapsulation method of the peptides. C57BL/6J mice were fed an obesogenic HFD (45% kcal from fat) with or without oral administration of calcium-ligated-alginate-microcapsule (CLAMs) or CLAMs with added PlnEF for twelve weeks. Feeding of encapsulated PlnEF was not associated with reduced weight gain or food intake compared to HF sham-fed mice or CLAMs-fed controls. However, the mice were unusual compared to other studies and exhibited rapid and excessive levels of weight gain and also exhibited significant intra-group variation. Although all CLAMs and L. plantarum fed mice showed improved oral glucose tolerance within nine weeks of feeding, no direct benefits of either L. plantarum or PlnEF on weight gain or food intake were found. Consistent with prior studies, feeding of wild-type L. plantarum increased ileal production of ZO-1 protein compared to feeding mice a PlnEF mutant. Therefore, this dissertation shows evidence for a role for bacteriocins in human and animal intestinal health and informs the search for possible direct signaling mechanisms between probiotic bacteria and the host intestine. |
| 일반주제명 | Microbiology. |
| 언어 | 영어 |
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