Characterization of the Invasive, Multidrug Resistant Non-typhoidal Salmonella Strain D23580 in a Murine Model of Infection.
Characterization of the Invasive, Multidrug Resistant Non-typhoidal Salmonella Strain D23580 in a Murine Model of Infection.
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DOI：
10.1371/journal.pntd.0003839
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发表时间：
2015-06
影响因子：
3.8
通讯作者：
Nickerson CA
中科院分区：
文献类型：
--
作者：
Yang J;Barrila J;Roland KL;Kilbourne J;Ott CM;Forsyth RJ;Nickerson CA
肠沙门氏菌鼠伤寒血清型的一个独特致病型ST313在撒哈拉以南非洲已成为幼儿和感染艾滋病毒的成年人致命菌血症的主要病因。D23580是ST313的一株多药耐药临床分离株，先前已表明其基因组以一种类似于更具人类特异性的病原体肠沙门氏菌伤寒血清型的方式发生了缩减。此后通过组织分布研究表明，D23580能够在鸡体内建立侵袭性感染。然而，尚不清楚ST313在自然感染过程后是否能在非人类宿主中引起致命疾病。在此我们报告，D23580在经口感染的小鼠模型中引起致命的侵袭性疾病。D23580在雌性BALB/c小鼠中的半数致死量（LD50）为4.7×10⁵菌落形成单位（CFU）。感染后3天和5天进行的组织分布研究证实，与特征明确的鼠伤寒沙门氏菌菌株SL1344相比，D23580能够更迅速地在小鼠的脾脏、肠系膜淋巴结和胆囊中定植。与SL1344相比，D23580对酸胁迫表现出更强的抗性，这可能有助于提高其在胃肠道以及细胞内生命周期中的存活能力。有趣的是，与SL1344、伤寒沙门氏菌菌株Ty2和ST313菌株A130相比，D23580还表现出更强的游动性。生化测试显示，D23580与SL1344有许多相似的代谢特征，但在Voges - Proskauer试验和过氧化氢酶试验以及蜜二糖和肌醇利用方面存在一些显著差异。这些结果代表了首次对ST313菌株在整个疾病自然进展过程中进行的全程感染研究，并为正在进行的和未来对D23580致病性的研究提供了一个基准。
一种致命的非伤寒型沙门氏菌已成为撒哈拉以南非洲侵袭性疾病的主要病因。对这种新型沙门氏菌序列型ST313的初步基因组分析表明，尽管从技术上它被归类为鼠伤寒沙门氏菌（一种具有广泛宿主范围的血清型），但它可能正在朝着更具人类特异性的“类伤寒”病原体进化。然而，最近已证明ST313菌株确实能够在鸡体内建立侵袭性和破坏性感染。尽管有这些重要发现，但由于尚未有研究追踪疾病进展的整个自然过程，所以尚不清楚ST313是否能在非人类宿主中引起致命疾病。因此，没有关于任何ST313菌株的半数致死量（LD50）的数据。这是一个重要的指标，因为LD50值将作为旨在理解毒力与ST313感染相关的表型和分子遗传特性之间关系的机制研究的一个基准。在此我们报告D23580在BALB/c小鼠中引起致命疾病，并确定了经口感染后的LD50。表型特征显示D23580与“经典”鼠伤寒菌株SL1344在组织分布、抗酸胁迫和生化利用方面存在明显差异。
A distinct pathovar of Salmonella enterica serovar Typhimurium, ST313, has emerged in sub-Saharan Africa as a major cause of fatal bacteremia in young children and HIV-infected adults. D23580, a multidrug resistant clinical isolate of ST313, was previously shown to have undergone genome reduction in a manner that resembles that of the more human-restricted pathogen, Salmonella enterica serovar Typhi. It has since been shown through tissue distribution studies that D23580 is able to establish an invasive infection in chickens. However, it remains unclear whether ST313 can cause lethal disease in a non-human host following a natural course of infection. Herein we report that D23580 causes lethal and invasive disease in a murine model of infection following peroral challenge. The LD50 of D23580 in female BALB/c mice was 4.7 x 105 CFU. Tissue distribution studies performed 3 and 5 days post-infection confirmed that D23580 was able to more rapidly colonize the spleen, mesenteric lymph nodes and gall bladder in mice when compared to the well-characterized S. Typhimurium strain SL1344. D23580 exhibited enhanced resistance to acid stress relative to SL1344, which may lend towards increased capability to survive passage through the gastrointestinal tract as well as during its intracellular lifecycle. Interestingly, D23580 also displayed higher swimming motility relative to SL1344, S. Typhi strain Ty2, and the ST313 strain A130. Biochemical tests revealed that D23580 shares many similar metabolic features with SL1344, with several notable differences in the Voges-Proskauer and catalase tests, as well alterations in melibiose, and inositol utilization. These results represent the first full duration infection study using an ST313 strain following the entire natural course of disease progression, and serve as a benchmark for ongoing and future studies into the pathogenesis of D23580. A deadly form of non-typhoidal Salmonella has emerged as a major cause of invasive disease in sub-Saharan Africa. Initial genomic profiling of this novel Salmonella sequence type, ST313, indicated that although it is technically classified as S. Typhimurium (a serovar characterized by a broad host range), it may be evolving towards becoming a more human-specific, ‘typhoid-like’ pathogen. However, it was recently demonstrated that ST313 strains were indeed able to establish an invasive and damaging infection in chickens. Despite these important findings, it remains unclear whether ST313 is able to cause lethal disease in a non-human host, since no study has yet followed the entire natural course of disease progression. As such, there are no data available concerning the median lethal dose (LD50) of any ST313 strain. This is an important metric, as the LD50 value will serve as a benchmark for mechanistic studies focused on understanding the relationship between virulence and the phenotypic and molecular genetic attributes associated with ST313 infections. Here we report that D23580 causes lethal disease in BALB/c mice and determined the LD50 following peroral challenge. Phenotypic characterization revealed distinct differences in tissue distribution, acid stress resistance, and biochemical utilization between D23580 and the ‘classic’ Typhimurium strain SL1344.
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影响因子：
168.9
作者：
Feasey, Nicholas A.;Dougan, Gordon;Kingsley, Robert A.;Heyderman, Robert S.;Gordon, Melita A.
通讯作者：
Gordon, Melita A.
DOI：
10.1111/j.1574-695x.2000.tb01498.x
发表时间：
2000-09-01
影响因子：
--
作者：
Kariuki, S;Oundo, JO;Hart, CA
通讯作者：
Hart, CA
影响因子：
3.2
作者：
FOSTER, JW;HALL, HK
通讯作者：
HALL, HK
影响因子：
2.2
作者：
Goh, Yun Shan;MacLennan, Calman A.
通讯作者：
MacLennan, Calman A.
影响因子：
4.2
作者：
Kalai Chelvam K;Chai LC;Thong KL
通讯作者：
Thong KL