Recombinant production of a diffusible signal factor inhibits Salmonella invasion and animal carriage.
Recombinant production of a diffusible signal factor inhibits Salmonella invasion and animal carriage.
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DOI：
10.1080/19490976.2023.2208498
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发表时间：
2023-01
期刊：
影响因子：
12.2
通讯作者：
中科院分区：
文献类型：
--
作者：
肠道复杂的化学环境很大程度上是由常驻微生物群的代谢产物决定的。肠道病原体经过优雅的进化，在肠道中茁壮成长，它们利用这些化学产品作为信号来识别特定的生态位并促进其生存和毒力。我们之前的工作表明，在肠道内发现的一类特定的群体感应分子，称为扩散信号因子（DSF），可以发出抑制沙门氏菌组织侵袭的信号，从而定义了该病原体识别其位置并调节毒力以优化其生存的方法。在这里，我们确定了 DSF 的重组生产是否可以降低体外和体内沙门氏菌的毒力。我们发现，通过添加编码脂肪酸烯酰辅酶A脱水酶/硫酯酶的单个外源基因，可以在大肠杆菌中重组产生沙门氏菌入侵最有效的抑制物顺式2-十六碳烯酸（c2-HDA），并且重组菌株与沙门氏菌共培养通过抑制沙门氏菌这种基本毒力功能所需的基因，有效抑制组织入侵。使用经过充分表征的大肠杆菌 Nissle 1917 菌株和鸡感染模型，我们发现重组 DSF 生产菌株可以在大肠中稳定维持。此外，挑战研究表明，这种重组生物体可以显着减少沙门氏菌在盲肠（该动物物种的携带部位）的定植。因此，这些发现描述了一种可能的方式，通过对定植和毒力所必需的功能进行原位化学操作，可以影响沙门氏菌在动物中的毒力。尽管我们尽了最大努力，农业动物沙门氏菌感染仍然持续存在，对食品安全构成威胁。事实证明，很少有措施（如果有的话）可以有效减少食品动物体内沙门氏菌的携带，而食品动物是这种病原体的主要来源。抗生素无法有效减少感染，只会加剧全球抗菌素耐药性危机。另一种选择是寻求新的方法，通过防止沙门氏菌在牲畜和家禽中定殖来减少沙门氏菌疾病和携带。在这里，我们描述了一种针对入侵的方法，入侵是沙门氏菌携带和动物疾病所必需的功能。我们证明，能够稳定定植于动物肠道的重组大肠杆菌菌株可以产生一种有效的化学入侵抑制剂，即可扩散信号因子顺式2十六碳烯酸，从而提供了一种直接影响动物宿主内沙门氏菌毒力的方法。因此，这些研究可能提供一种减少这种病原体在生产动物中携带的途径，从而减少疾病向人类的传播。
The complex chemical environment of the intestine is defined largely by the metabolic products of the resident microbiota. Enteric pathogens, elegantly evolved to thrive in the gut, use these chemical products as signals to recognize specific niches and to promote their survival and virulence. Our previous work has shown that a specific class of quorum-sensing molecules found within the gut, termed diffusible signal factors (DSF), signals the repression of Salmonella tissue invasion, thus defining a means by which this pathogen recognizes its location and modulates virulence to optimize its survival. Here, we determined whether the recombinant production of a DSF could reduce Salmonella virulence in vitro and in vivo. We found that the most potent repressor of Salmonella invasion, cis-2-hexadecenoic acid (c2-HDA), could be recombinantly produced in E. coli by the addition of a single exogenous gene encoding a fatty acid enoyl-CoA dehydratase/thioesterase and that co-culture of the recombinant strain with Salmonella potently inhibited tissue invasion by repressing Salmonella genes required for this essential virulence function. Using the well characterized E. coli Nissle 1917 strain and a chicken infection model, we found that the recombinant DSF-producing strain could be stably maintained in the large intestine. Further, challenge studies demonstrated that this recombinant organism could significantly reduce Salmonella colonization of the cecum, the site of carriage in this animal species. These findings thus describe a plausible means by which Salmonella virulence may be affected in animals by in situ chemical manipulation of functions essential for colonization and virulence. Despite our best efforts, infections of agricultural animals with Salmonella persist, posing threats to food safety. Few, if any, measures have proven effective in reducing Salmonella carriage in animals used for food, a major source of this pathogen. Antibiotics are ineffective at curtailing infection and have served only to exacerbate the global crisis of antimicrobial resistance. The alternative then is to seek novel means to reduce Salmonella disease and carriage by preventing its colonization of livestock and poultry. Here we describe an approach targeting invasion, a function essential for Salmonella carriage and disease in animals. We show that a potent chemical inhibitor of invasion, the diffusible signal factor cis-2 hexadecenoic acid, can be produced by recombinant E. coli strains capable of stably colonizing the animal intestine, providing a means to directly affect the virulence of Salmonella within an animal host. These studies may thus provide a route to reduce the carriage of this pathogen in production animals and thus the spread of disease to humans.
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影响因子：
6.4
作者：
Golubeva YA;Ellermeier JR;Cott Chubiz JE;Slauch JM
通讯作者：
Slauch JM
影响因子：
3.6
作者：
Hung CC;Garner CD;Slauch JM;Dwyer ZW;Lawhon SD;Frye JG;McClelland M;Ahmer BM;Altier C
通讯作者：
Altier C
影响因子：
3.7
作者：
Lawhon SD;Khare S;Rossetti CA;Everts RE;Galindo CL;Luciano SA;Figueiredo JF;Nunes JE;Gull T;Davidson GS;Drake KL;Garner HR;Lewin HA;Bäumler AJ;Adams LG
通讯作者：
Adams LG
影响因子：
3.7
作者：
Cukrowska, B;Lodínova-Zádníková, R;Tlaskalová-Hogenová, H
通讯作者：
Tlaskalová-Hogenová, H
影响因子：
3.2
作者：
Huang, Yanyan;Suyemoto, Mitsu;Altier, Craig
通讯作者：
Altier, Craig