Invasive non-typhoidal Salmonella typhimurium ST313 are not host-restricted and have an invasive phenotype in experimentally infected chickens.
Invasive non-typhoidal Salmonella typhimurium ST313 are not host-restricted and have an invasive phenotype in experimentally infected chickens.
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DOI：
10.1371/journal.pntd.0002487
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发表时间：
2013
影响因子：
3.8
通讯作者：
Wigley P
中科院分区：
文献类型：
--
作者：
Parsons BN;Humphrey S;Salisbury AM;Mikoleit J;Hinton JC;Gordon MA;Wigley P
肠道沙门氏菌血清型鼠伤寒序列型（ST）313是撒哈拉以南非洲侵袭性非伤寒沙门氏菌病的主要原因。目前还没有发现动物宿主，有人认为ST 313适合人类，可能通过人与人之间的传播发生传播。在这里，我们表明ST 313在鸡和人类中引起严重的侵入性感染。用ST 313分离株D23580和Q456经口感染鸡导致脾脏和肝脏的快速感染，在感染后3天，所有在这些部位感染的鸡都被感染。相比之下，定义明确的ST 19 S.鼠伤寒杆菌分离株F98和4/74引起侵袭性疾病的速度较慢。ST 19和ST 313均引起肝脾肿大，这在ST 313感染的动物中最为明显。在感染后3天和7天，与ST 19相比，ST 313分离株感染的禽类胃肠道定植较低。组织学检查和回肠中CXCL趋化因子的表达表明，D23580（ST 313）和4/74（ST 19）菌株在感染后3天均引起CXCL表达增加，并且D23580的回肠中CXCL表达显着高于4/74感染鸟类。在感染后7天，D23580的回肠中出现趋化因子表达减少，但4/74感染的鸟中没有。组织学分析显示，D23580感染导致快速炎症和病理学，包括感染后3天的绒毛变平和融合，以及随后7天的消退。相比之下，4/74在感染后3天诱导较少的炎症和病理。所呈现的数据证明ST 313能够在非人类宿主中引起侵袭性疾病。鸡感染的快速侵袭性，加上下消化道定植，支持ST 313是S.鼠伤寒沙门氏菌已进化成为一种系统性病原体，可在几种宿主中引起疾病。 鼠伤寒沙门氏菌通常引起人类食源性腹泻感染。最近S.鼠伤寒在非洲出现，与侵袭性和往往致命的疾病有关，特别是在感染艾滋病毒的成年人和患有疟疾或营养不良的儿童中。对这些序列型（ST）313分离株的分析发现，与通常导致人类腹泻的ST 19基因型相比，基因组发生了显著降解。其特征是在人类适应的伤寒沙门氏菌中观察到的假基因和缺失。这导致了ST 313已经特别适应人类的假设。在这里，我们表明ST 313也会导致鸡的侵袭性疾病，这是人类沙门氏菌感染的常见来源。与人类一样，ST 313菌株比ST 19 S更具侵袭性。鼠伤寒沙门氏菌，也导致较少的肠道定植。然而，与沙门氏菌血清型与鸡的侵袭性疾病相关不同，ST 313引起肠道炎症和损伤。这些发现表明，ST 313对人类没有宿主限制，并且可能已经进化到在一系列宿主中引起更具侵袭性的疾病。我们强调，包括鸡在内的动物仍然可能是ST 313的来源，需要对非洲ST 313的潜在动物宿主进行进一步的流行病学研究。
Salmonella enterica serovar Typhimurium Sequence Type (ST) 313 is a major cause of invasive non-Typhoidal salmonellosis in sub-Saharan Africa. No animal reservoir has been identified, and it has been suggested that ST313 is adapted to humans and transmission may occur via person-to-person spread. Here, we show that ST313 cause severe invasive infection in chickens as well as humans. Oral infection of chickens with ST313 isolates D23580 and Q456 resulted in rapid infection of spleen and liver with all birds infected at these sites by 3 days post-infection. In contrast, the well-defined ST19 S. Typhimurium isolates F98 and 4/74 were slower to cause invasive disease. Both ST19 and ST313 caused hepatosplenomegaly, and this was most pronounced in the ST313-infected animals. At 3 and 7 days post-infection, colonization of the gastrointestinal tract was lower in birds infected with the ST313 isolates compared with ST19. Histological examination and expression of CXCL chemokines in the ileum showed that both D23580 (ST313) and 4/74 (ST19) strains caused increased CXCL expression at 3 days post-infection, and this was significantly higher in the ileum of D23580 vs 4/74 infected birds. At 7 days post-infection, reduced chemokine expression occurred in the ileum of the D23580 but not 4/74-infected birds. Histological analysis showed that D23580 infection resulted in rapid inflammation and pathology including villous flattening and fusion at 3 days post-infection, and subsequent resolution by 7 days. In contrast, 4/74 induced less inflammation and pathology at 3 days post-infection. The data presented demonstrate that ST313 is capable of causing invasive disease in a non-human host. The rapid invasive nature of infection in the chicken, coupled with lower gastrointestinal colonization, supports the hypothesis that ST313 is a distinct pathovariant of S. Typhimurium that has evolved to become a systemic pathogen that can cause disease in several hosts. Salmonella enterica serovar Typhimurium usually causes foodborne diarrheal infections in humans. Recently variants of S. Typhimurium have emerged in Africa associated with invasive and often fatal disease, especially in adults infected by HIV and children with malaria or malnutrition. Analysis of these Sequence Type (ST) 313 isolates has identified significant genome degradation, compared with the ST19 genotype that typically causes diarrhea in humans. This is characterised by pseudogenes and deletions observed in the human-adapted S.Typhi. This has led to the hypothesis that the ST313 has become specifically adapted to humans. Here, we show ST313 also cause invasive disease in chickens, a common source of human Salmonella infection. As in humans, ST313 strains are more invasive than ST19 S. Typhimurium, and also cause less intestinal colonization. However, unlike Salmonella serotypes associated with invasive disease in the chicken, ST313 causes inflammation and damage to the intestine. These findings suggest that ST313 is not host-restricted to humans, and may have evolved to cause a more invasive disease in a range of hosts. We highlight the fact that animals, including chickens, could still be a source of ST313 and that further epidemiological research is needed into potential animal reservoirs of ST313 in Africa.
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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.
影响因子：
3.1
作者：
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影响因子：
1.8
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7
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Parkhill, Julian
影响因子：
5.8
作者：
Wigley, P;Hulme, SD;Barrow, PA
通讯作者：
Barrow, PA