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Vibrio cholerae colonization of the fly rectum and activation of natural competen

霍乱弧菌在果蝇直肠的定植及天然活性物质的激活

基本信息

批准号：
8906731
负责人：
PAULA I WATNICK
金额：
$ 22.1万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-07 至 2017-01-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Vibrio cholerae is an environmental Gram-negative bacterium and an epidemic and pandemic human diarrheal pathogen. Rapid evolution of the V. cholerae genome in the environment has resulted in exchange of immunity determinants and acquisition of antibiotic resistance traits. These changes have periodically expanded the pool of susceptible individuals or complicated treatment of disease. Natural competence is the ability of bacteria to take up environmental DNA, and the acquisition of new genes through this process is known as horizontal gene transfer. Recently, investigators have found that V. cholerae becomes naturally competent and is able to incorporate new DNA into its genome when cultured under conditions in which quorum sensing is activated and chitin is present. Because V. cholerae abundance in estuaries sometimes correlates with the presence of zooplankton, and these organisms are a rich source of chitin, their exoskeletons are hypothesized to be the environmental surface on which natural competence is activated and the V. cholerae genome evolves. However, chitin, one of the most abundant polymers found on earth, is a surface component of many organisms including algae, fungi, and insects. We propose that, if a host's microbiota transfers particularly advantageous genetic elements to a colonizing pathogen, even a less abundant or less frequently encountered environmental host may have a great impact on a pathogen's success. Multiple publications have reported isolation of V. cholerae, other enteric pathogens, and human commensal bacteria from house flies. In the vicinity of hospitals and farms, the bacteria recovered from flies are often resistant to multiple antibiotics. Therefore, we hypothesized that the fly might provide a rich environment for acquisition of genes encoding virulence traits and antibiotic resistance. Using the fruit fly Drosophila melanogaster as a model, we recently discovered that V. cholerae forms a dense biofilm on the chitinous lining of an intestinal compartment known as the rectum. Preliminary results suggest that quorum and chitin sensing are operative in this compartment, leading to activation of the genes required for natural competence. Here we propose to examine the structures, signals, and regulatory systems that contribute to V. cholerae colonization of the house fly rectum, to study regulation of natural competence genes in the fly rectum, and then to assess horizontal gene transfer in the fly. These studies may impart relevance to the hundreds of studies of V. cholerae biofilm formation in LB broth, may reveal an environmental niche in which V. cholerae natural competence is activated, and may suggest fly control as a simple method to limit the transfer of new virulence and antibiotic resistance traits to pathogenic V. cholerae.

描述（由申请人提供）：霍乱弧菌是一种环境革兰氏阴性菌，是一种流行和大流行的人类腹泻病原体。霍乱弧菌基因组在环境中的快速进化导致了免疫决定因素的交换和抗生素耐药性状的获得。这些变化周期性地扩大了易感个体的数量或使疾病的治疗复杂化。自然能力是细菌吸收环境DNA的能力，通过这一过程获得新基因被称为水平基因转移。最近，研究人员发现，霍乱弧菌在群体感应被激活和几丁质存在的条件下培养时，变得自然胜任，能够将新的DNA整合到其基因组中。由于霍乱弧菌在河口的丰度有时与浮游动物的存在有关，而这些生物是几丁质的丰富来源，因此它们的外骨骼被假设为自然能力被激活和霍乱弧菌基因组进化的环境表面。然而，几丁质是地球上发现的最丰富的聚合物之一，是许多生物的表面成分，包括藻类、真菌和昆虫。我们认为，如果宿主的微生物群将特别有利的遗传元素转移给定殖病原体，那么即使是不那么丰富或不太频繁遇到的环境宿主也可能对病原体的成功产生重大影响。多篇出版物报道了从家蝇中分离出霍乱弧菌、其他肠道病原体和人类共生细菌。在医院和农场附近，从苍蝇身上发现的细菌通常对多种抗生素具有耐药性。因此,我们