Pathogenomic inference of virulence-associated genes in Leptospira interrogans.
Pathogenomic inference of virulence-associated genes in Leptospira interrogans.
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DOI：
10.1371/journal.pntd.0002468
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发表时间：
2013
影响因子：
3.8
通讯作者：
Matthias MA
中科院分区：
文献类型：
--
作者：
Lehmann JS;Fouts DE;Haft DH;Cannella AP;Ricaldi JN;Brinkac L;Harkins D;Durkin S;Sanka R;Sutton G;Moreno A;Vinetz JM;Matthias MA
钩端螺旋体病是由钩端螺旋体属的螺旋体引起的一种全球性的重要的、被忽视的人畜共患传染病。由于致病性钩端螺旋体的遗传转化在技术上仍然是有限的，系统生物学病原体组学方法被用来推断钩端螺旋体毒力基因的全基因组比较培养减毒钩端螺旋体赖血清型与它的毒力，同基因的父母。在发现非同义突变的11个病原体特异性蛋白质编码基因中，鉴定了一种具有宿主细胞cAMP升高活性的推定可溶性腺苷酸环化酶和两个先前未研究的功能未知的15个成员旁系同源基因家族的成员。这个基因家族也是唯一发现的α-变形菌Bartonella bacilliformis和Bartonella australis地理上仅限于安第斯山脉和澳大利亚，分别。致病性钩端螺旋体和这两种巴尔通体如何共享这个扩展的基因家族仍然是一个进化之谜。体内表达分析表明，在减毒筛选中鉴定的10/11个钩端螺旋体基因上调，以及旁系同源基因家族成员在体内的组织特异性上调，表明在毒力和宿主-病原体相互作用中的直接作用。这里的病原体组学实验设计作为研究细菌致病性和毒力的功能系统生物学方法是可推广的，并应鼓励其他病原体的类似实验研究。钩端螺旋体病是世界范围内最常见的动物传播疾病之一。它很重要，因为它在热带和亚热带地区与卫生条件差和农业有关，通常会导致致命的发热性疾病。钩端螺旋体病可能是流行病，与自然灾害和洪水有关，或在热带地区流行。目前尚不清楚钩端螺旋体是如何引起疾病的，以及为什么不同的菌株会导致不同的疾病严重程度。在这项研究中，我们减毒（削弱）一个高致病力的菌株L。通过在体外培养几个月的时间，在减毒过程之前和之后的全基因组序列的比较揭示了一小部分基因发生了突变，因此与毒力相关。我们发现了一个假定的可溶性腺苷酸环化酶与宿主细胞cAMP升高活性，与免疫逃避和一个新的基因家族，在体内急性仓鼠感染过程中上调的影响。有趣的是，杆状巴尔通体和澳大利亚巴尔通体也具有我们在致病性钩端螺旋体中描述的这个独特的基因家族。这些信息有助于我们了解钩端螺旋体的演变和发病机制。
Leptospirosis is a globally important, neglected zoonotic infection caused by spirochetes of the genus Leptospira. Since genetic transformation remains technically limited for pathogenic Leptospira, a systems biology pathogenomic approach was used to infer leptospiral virulence genes by whole genome comparison of culture-attenuated Leptospira interrogans serovar Lai with its virulent, isogenic parent. Among the 11 pathogen-specific protein-coding genes in which non-synonymous mutations were found, a putative soluble adenylate cyclase with host cell cAMP-elevating activity, and two members of a previously unstudied ∼15 member paralogous gene family of unknown function were identified. This gene family was also uniquely found in the alpha-proteobacteria Bartonella bacilliformis and Bartonella australis that are geographically restricted to the Andes and Australia, respectively. How the pathogenic Leptospira and these two Bartonella species came to share this expanded gene family remains an evolutionary mystery. In vivo expression analyses demonstrated up-regulation of 10/11 Leptospira genes identified in the attenuation screen, and profound in vivo, tissue-specific up-regulation by members of the paralogous gene family, suggesting a direct role in virulence and host-pathogen interactions. The pathogenomic experimental design here is generalizable as a functional systems biology approach to studying bacterial pathogenesis and virulence and should encourage similar experimental studies of other pathogens. Leptospirosis is one of the most common diseases transmitted by animals worldwide. It is important because it causes an often lethal febrile illnesses in tropical and subtropical areas associated with poor sanitation and agriculture. Leptospirosis may be epidemic, associated with natural disasters and flooding, or endemic in tropical regions. It is unknown how Leptospira cause disease and why different strains cause different severity of illness. In this study we attenuated (weakened) a highly virulent strain of L. interrogans by culturing it in vitro over several months. Comparison of the whole genome sequence before and after the attenuation process revealed a small set of genes that were mutated, and therefore associated with virulence. We discovered a putative soluble adenylate cyclase with host cell cAMP elevating activity, with implications for immune evasion and a new gene family that is upregulated in vivo during acute hamster infection. Interestingly, both Bartonella bacilliformis and Bartonella australis also have this unique gene family we describe in pathogenic Leptospira. This information aids in our understanding of Leptospira evolution and pathogenesis.
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影响因子：
4.5
作者：
Guy L;Nystedt B;Toft C;Zaremba-Niedzwiedzka K;Berglund EC;Granberg F;Näslund K;Eriksson AS;Andersson SG
通讯作者：
Andersson SG
DOI：
10.1073/pnas.79.10.3162
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
LEPPLA, SH
通讯作者：
LEPPLA, SH
DOI：
10.4269/ajtmh.2010.09-0778
发表时间：
2010-06-01
影响因子：
3.3
作者：
Kosoy, Michael;Bai, Ying;Peruski, Leonard F.
通讯作者：
Peruski, Leonard F.
影响因子：
4.2
作者：
Liao S;Sun A;Ojcius DM;Wu S;Zhao J;Yan J
通讯作者：
Yan J
影响因子：
3.1
作者：
Bensing, BA;Siboo, IR;Sullam, PM
通讯作者：
Sullam, PM