Intraspecies variation in the emergence of hyperinfectious bacterial strains in nature.
Intraspecies variation in the emergence of hyperinfectious bacterial strains in nature.
复制标题
自然界中过度感染细菌菌株出现的种内变化。
DOI：
10.1371/journal.ppat.1002647
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发表时间：
2012
期刊：
影响因子：
6.7
通讯作者：
Mahan MJ
中科院分区：
文献类型：
--
作者：
Heithoff DM;Shimp WR;House JK;Xie Y;Weimer BC;Sinsheimer RL;Mahan MJ
沙门氏菌是一个主要的健康问题，因为它在食品和水供应中流行，多重耐药菌株的发病率上升，以及与疾病严重程度增加相关的新菌株的出现。对病原体出现的深入了解来自动物传代研究，其中毒力在感染过程中通常会增加。然而，这些研究并没有解决选定的菌株子集在感染过程中毒力显着增加的前景——这一前景对人类和动物健康具有重大影响。我们的研究结果表明，某些肠沙门氏菌菌株变得高毒力（LD50 降低 100 倍）的能力比其他菌株更为明显。超传染性沙门氏菌是该物种中毒性最强的。仅限于某些血清型；并且更有能力杀死接种疫苗的动物。这些菌株表现出快速（且快速可逆）转变为毒性较低的状态，并伴随着更具竞争性的离体生长，这可能有助于在自然界中的维持。高毒力表型与微生物致病性增加（定植、细胞毒素产生、杀细胞活性）相关，同时还与受感染细胞内先天免疫细胞因子反应的改变（IFN-β；IL-1β；IL-6；IL-10）相关。基因表达分析显示，高度感染性菌株的 PhoP/PhoQ、PhoR/PhoB 和 ArgR 调节子内的基因转录发生改变，导致经典毒力功能（例如 SPI-1；SPI-2 效应器）和细胞生理/代谢（营养/酸应激）相关功能的表达发生变化。由于高度传染性菌株对人类和动物健康构成潜在风险，减轻这些潜在食源性污染物的努力可能会避免负面的公共卫生影响和与行业相关的损失。沙门氏菌病继续危害人类健康、动物福利和现代农业。制定全面的控制计划需要了解病原体如何出现并表达导致疾病发病率和严重程度增加的特征。众所周知，动物传代通常会导致毒力增加。然而，我们的研究结果表明，在某些沙门氏菌分离株中，传代后毒力显着增加的能力比其他沙门氏菌分离株更为普遍。由此产生的超级传染性菌株属于已报道的毒性最强的沙门氏菌菌株。仅限于某些血清型；并能够超越接种疫苗的动物所赋予的免疫力。高毒力的诱导是对环境条件的微妙变化作出反应，并且可能在其他沙门氏菌血清型中通过某些宿主和/或暴露于某些环境变量后发生；这种反应可能在微生物领域很常见。因此，畜牧生产固有的管理实践和环境条件有可能无意中引发高毒力（例如饮食、畜群规模、接触牲畜废物和/或抗菌药物）。从农场管理的角度来看，必须仔细考虑风险管理策略，以减少这些潜在食源性污染物的出现/持续存在，以保障公众健康并减少与行业相关的损失。
Salmonella is a principal health concern because of its endemic prevalence in food and water supplies, the rise in incidence of multi-drug resistant strains, and the emergence of new strains associated with increased disease severity. Insights into pathogen emergence have come from animal-passage studies wherein virulence is often increased during infection. However, these studies did not address the prospect that a select subset of strains undergo a pronounced increase in virulence during the infective process- a prospect that has significant implications for human and animal health. Our findings indicate that the capacity to become hypervirulent (100-fold decreased LD50) was much more evident in certain S. enterica strains than others. Hyperinfectious salmonellae were among the most virulent of this species; restricted to certain serotypes; and more capable of killing vaccinated animals. Such strains exhibited rapid (and rapidly reversible) switching to a less-virulent state accompanied by more competitive growth ex vivo that may contribute to maintenance in nature. The hypervirulent phenotype was associated with increased microbial pathogenicity (colonization; cytotoxin production; cytocidal activity), coupled with an altered innate immune cytokine response within infected cells (IFN-β; IL-1β; IL-6; IL-10). Gene expression analysis revealed that hyperinfectious strains display altered transcription of genes within the PhoP/PhoQ, PhoR/PhoB and ArgR regulons, conferring changes in the expression of classical virulence functions (e.g., SPI-1; SPI-2 effectors) and those involved in cellular physiology/metabolism (nutrient/acid stress). As hyperinfectious strains pose a potential risk to human and animal health, efforts toward mitigation of these potential food-borne contaminants may avert negative public health impacts and industry-associated losses. Salmonellosis continues to compromise human health, animal welfare, and modern agriculture. Developing a comprehensive control plan requires an understanding of how pathogens emerge and express traits that confer increased incidence and severity of disease. It is well-established that animal passage often results in increased virulence; however, our findings indicate that the capacity to undergo a pronounced increase in virulence after passage was much more prevalent in certain Salmonella isolates than in others. The resultant hyperinfectious strains are among the most virulent salmonellae reported; were restricted to certain serotypes; and were able to override the immunity conferred in vaccinated animals. The induction of hypervirulence was responsive to subtle changes in environmental conditions and, potentially, may occur in other salmonellae serotypes after passage through certain hosts and/or exposure to certain environmental variables; a response that may be common across the microbial realm. Thus, management practices and environmental conditions inherent to livestock production have the potential to inadvertently trigger hypervirulence (e.g., diet; herd size; exposure to livestock waste and/or antimicrobials). From a farm management perspective, careful consideration must be given to risk-management strategies that reduce emergence/persistence of these potential food-borne contaminants to safeguard public health and reduce industry-associated losses.
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影响因子：
8.7
作者：
Broz P;Monack DM
通讯作者：
Monack DM
影响因子：
3.7
作者：
Aziz RK;Kansal R;Aronow BJ;Taylor WL;Rowe SL;Kubal M;Chhatwal GS;Walker MJ;Kotb M
通讯作者：
Kotb M
影响因子：
4.2
作者：
Besser, TE;Richards, BL;Hancock, DD
通讯作者：
Hancock, DD
DOI：
10.1007/978-0-387-78885-2_10
发表时间：
2008-01-01
期刊：
BACTERIAL SIGNAL TRANSDUCTION: NETWORKS AND DRUG TARGETS
影响因子：
--
作者：
Beier, Dagmar;Gross, Roy
通讯作者：
Gross, Roy
影响因子：
3.1
作者：
Bower, Jean M.;Gordon-Raagas, Hannah B.;Mulvey, Matthew A.
通讯作者：
Mulvey, Matthew A.