利用阿斯匹林来启动被感染宿主内细菌基因的表达，研究人员发现了一种研究宿主与致病原间相互作用的安全又容易的新方法，研究成果在线发表在10月出版的《自然—方法学》期刊上。
当某种细菌感染了宿主的某一器官时，这种细菌会表达出一系列不同的基因。这些基因在不同的时间被表达出来，因此对微生物具有不同的毒性。但是，因为在严格受控的动物试验中缺乏安全的选择性调控细菌基因的表达，所以，对细菌基因表达过程的研究受到了阻碍。
Eduardo Santero和同事报告说，一种与乙酰水杨酸即阿斯匹林相呼应的受控基因表达回路可以被整合进细菌中，用于控制特定基因的表达。为了从原理上证明新方法的有效性，他们对一种沙门氏菌实施基因工程改造，让它表达出一种能将无毒化学物质转化为有毒物质的酶，然后，再将这种转基因细菌注射进小鼠体内。他们发现，调控阿斯匹林能够打开被沙门氏菌感染的细胞中的嵌入基因，并杀死它们。这种原理证明性试验表明，新方法可广泛应用于宿主—致病体间相互作用的研究。（科学时报）
原始出处:
Nature Methods - 4, 937 - 942 (2007)
Published online: 7 October 2007; | doi:10.1038/nmeth1107
In vivo gene regulation in Salmonella spp. by a salicylate-dependent control circuit
José Luis Royo1, 2, 4, Pablo Daniel Becker2, 4, Eva María Camacho1, Angel Cebolla3, Claudia Link2, Eduardo Santero1 & Carlos Alberto Guzmán2
1 Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide–Consejo Superior de Investigaciones Científicas, Carretera, Utrera, Km 1, E-41013 Sevilla, Spain.
2 Department of Vaccinology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
3 Biomedal SL, Avda. Américo Vespucio 5, Blq E 1a planta, E-41092 Sevilla, Spain.
4 These authors contributed equally to this work.
Correspondence should be addressed to Eduardo Santero esansan@upo.es
Systems allowing tightly regulated expression of prokaryotic genes in vivo are important for performing functional studies of bacterial genes in host-pathogen interactions and establishing bacteria-based therapies. We integrated a regulatory control circuit activated by acetyl salicylic acid (ASA) in attenuated Salmonella enterica that carries an expression module with a gene of interest under control of the XylS2-dependent Pm promoter. This resulted in 20–150-fold induction ex vivo. The regulatory circuit was also efficiently induced by ASA when the bacteria resided in eukaryotic cells, both in vitro and in vivo. To validate the circuit, we administered Salmonella spp., carrying an expression module encoding the 5-fluorocytosine–converting enzyme cytosine deaminase in the bacterial chromosome or in a plasmid, to mice with tumors. Induction with ASA before 5-fluorocytosine administration resulted in a significant reduction of tumor growth. These results demonstrate the usefulness of the regulatory control circuit to selectively switch on gene expression during bacterial infection.
