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微生物群衍生的短链脂肪酸调节共生和毒力所需决定因素的表达。

Microbiota-Derived Short-Chain Fatty Acids Modulate Expression of Determinants Required for Commensalism and Virulence.

作者信息

Luethy Paul M, Huynh Steven, Ribardo Deborah A, Winter Sebastian E, Parker Craig T, Hendrixson David R

机构信息

Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Produce Safety and Microbiology, USDA Agricultural Research Service, Albany, California, USA.

出版信息

mBio. 2017 May 9;8(3):e00407-17. doi: 10.1128/mBio.00407-17.

DOI:10.1128/mBio.00407-17
PMID:28487428
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5424204/
Abstract

promotes commensalism in the intestinal tracts of avian hosts and diarrheal disease in humans, yet components of intestinal environments recognized as spatial cues specific for different intestinal regions by the bacterium to initiate interactions in either host are mostly unknown. By analyzing a acetogenesis mutant defective in converting acetyl coenzyme A (Ac-CoA) to acetate and commensal colonization of young chicks, we discovered evidence for microbiota-derived short-chain fatty acids (SCFAs) and organic acids as cues recognized by that modulate expression of determinants required for commensalism. We identified a set of genes encoding catabolic enzymes and transport systems for amino acids required for growth whose expression was modulated by SCFAs. Transcription of these genes was reduced in the acetogenesis mutant but was restored upon supplementation with physiological concentrations of the SCFAs acetate and butyrate present in the lower intestinal tracts of avian and human hosts. Conversely, the organic acid lactate, which is abundant in the upper intestinal tract where colonizes less efficiently, reduced expression of these genes. We propose that microbiota-generated SCFAs and lactate are cues for to discriminate between different intestinal regions. Spatial gradients of these metabolites likely allow to locate preferred niches in the lower intestinal tract and induce expression of factors required for intestinal growth and commensal colonization. Our findings provide insights into the types of cues monitors in the avian host for commensalism and likely in humans to promote diarrheal disease. is a commensal of the intestinal tracts of avian species and other animals and a leading cause of diarrheal disease in humans. The types of cues sensed by to influence responses to promote commensalism or infection are largely lacking. By analyzing a acetogenesis mutant, we discovered a set of genes whose expression is modulated by lactate and short-chain fatty acids produced by the microbiota in the intestinal tract. These genes include those encoding catabolic enzymes and transport systems for amino acids that are required by for growth and intestinal colonization. We propose that gradients of these microbiota-generated metabolites are cues for spatial discrimination between areas of the intestines so that the bacterium can locate niches in the lower intestinal tract for optimal growth for commensalism in avian species and possibly infection of human hosts leading to diarrheal disease.

摘要

它促进禽类宿主肠道中的共生关系,并导致人类腹泻疾病,但该细菌识别为不同肠道区域特异性空间线索以在任一宿主中启动相互作用的肠道环境成分大多未知。通过分析一个在将乙酰辅酶A(Ac-CoA)转化为乙酸盐以及雏鸡共生定殖方面存在缺陷的产乙酸突变体,我们发现了微生物群衍生的短链脂肪酸(SCFAs)和有机酸作为被该细菌识别的线索的证据,这些线索调节共生所需决定因素的表达。我们鉴定出一组编码该细菌生长所需氨基酸分解代谢酶和转运系统的基因,其表达受SCFAs调节。这些基因的转录在产乙酸突变体中降低,但在用禽类和人类宿主下肠道中存在的生理浓度的SCFAs乙酸盐和丁酸盐补充后恢复。相反,在上肠道中大量存在且该细菌定殖效率较低的有机酸乳酸,降低了这些基因的表达。我们提出微生物群产生的SCFAs和乳酸是该细菌区分不同肠道区域的线索。这些代谢物的空间梯度可能使该细菌能够在下肠道中定位偏好的生态位,并诱导肠道生长和共生定殖所需因子的表达。我们的发现为该细菌在禽类宿主中监测共生关系以及可能在人类中促进腹泻疾病的线索类型提供了见解。该细菌是禽类和其他动物肠道的共生菌,也是人类腹泻疾病的主要原因。目前很大程度上缺乏该细菌感知以影响促进共生或感染反应的线索类型。通过分析一个产乙酸突变体,我们发现了一组基因,其表达受肠道微生物群产生的乳酸和短链脂肪酸调节。这些基因包括那些编码该细菌生长和肠道定殖所需氨基酸分解代谢酶和转运系统的基因。我们提出这些微生物群产生的代谢物梯度是肠道区域之间空间区分的线索,以便该细菌能够在禽类物种的下肠道中定位生态位以实现共生的最佳生长,并可能感染人类宿主导致腹泻疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f2c/5424204/5dd737894d09/mbo0021733000010.jpg
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