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）：弧菌霍乱是一种环境革兰氏阴性细菌，是一种流行病和大流行的人腹泻病原体。环境中霍乱基因组的快速演变导致了免疫决定因素和抗生素耐药性状的获取。这些变化已定期扩大了易感人群或对疾病的复杂治疗。自然能力是细菌吸收环境DNA的能力，并且通过此过程获得新基因的能力被称为水平基因转移。最近，研究人员发现，霍乱葡萄球菌具有自然能力，并且能够在激活法规传感并存在几丁质的条件下培养时将新的DNA纳入其基因组中。由于河口中的霍乱丰度有时与浮游动物的存在相关，而这些生物体是千元丰富的来源，因此它们的外骨骼被认为是激活自然能力的环境表面，并且V. cholerae Genome Genome Evolves。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。我们建议，如果宿主的微生物群将特别有利的遗传因素转移到定植病原体中，那么即使是较少或频繁遇到的环境宿主也可能对病原体的成功产生很大的影响。多个出版物报道了霍乱弧菌，其他肠道病原体和人类共生细菌的隔离。在医院和农场附近，从苍蝇中回收的细菌通常对多种抗生素有抵抗力。因此，我们假设苍蝇可能为获得编码毒力性状和抗生素耐药性的基因提供丰富的环境。将果蝇果蝇Melanogaster作为模型，我们最近发现，霍乱葡萄球菌在一个称为直肠的肠室的几架衬里上形成了致密的生物膜。初步结果表明，法定人数和几丁质感应在此隔室中是可行的，从而激活了自然能力所需的基因。在这里，我们建议检查有助于霍尔氏菌蝇直肠的霍乱菌定植的结构，信号和调节系统，以研究蝇直肠中自然能力基因的调节，然后评估果蝇中的水平基因转移。这些研究可能与LB肉汤中V.霍乱生物膜形成的数百项研究相关，可能会揭示一个环境细分市场，在该裂市场中，将V.霍乱的自然能力被激活，并可能建议将蝇蝇控制作为限制新的病毒性和抗生素耐药性特征转移到致病性V. Cholerae的简单方法。