Bacterial infection as assessed by in vivo gene expression
Bacterial infection as assessed by in vivo gene expression
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DOI：
10.1073/pnas.94.3.934
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发表时间：
1997-02-04
影响因子：
11.1
通讯作者：
Mahan, MJ
中科院分区：
文献类型：
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作者：
Heithoff, DM;Conner, CP;Mahan, MJ
体内表达技术（IVET）已用于鉴定在BALB/c小鼠和/或鼠培养的巨噬细胞感染期间特异性表达的>100种鼠伤寒沙门氏菌基因。这些基因的诱导被证明是在IVET选择条件下动物存活所必需的。其中一类体内诱导（ivi）基因iviVI-A和iviVI-B构成操纵子，其位于沙门氏菌基因组中具有低G+C含量的区域，并且可能是通过水平转移获得的。这些ipi基因编码预测的蛋白质，其类似于来自原核和真核病原体的粘附素和侵袭素（大肠杆菌[tia]，恶性疟原虫[PfEMP 1]），并已增选沙门氏菌毒力基因的PhoPQ调控回路。体内诱导分布的检查表明（i）许多ivi基因编码调节功能（例如，phoPQ和pmrAB），其用于增强毒力基因表达的敏感性和幅度（例如，spvB）;（ii）许多代谢基因的生化功能可能并不代表它们对毒力的唯一贡献;（iii）可从ipi基因的生化功能推断宿主生态;以及（iv）营养限制在发病机制中起双重信号作用：诱导补充宿主营养不足的代谢功能，并诱导立即存活并传播到随后的宿主地点所需的毒力功能。
In vivo expression technology (IVET) has been used to identify >100 Salmonella typhimurium genes that are specifically expressed during infection of BALB/c mice and/or murine cultured macrophages. Induction of these genes is shown to be required for survival in the animal under conditions of the IVET selection. One class of in vivo induced (ivi) genes, iviVI-A and iviVI-B, constitute an operon that resides in a region of the Salmonella genome with low G+C content and presumably has been acquired by horizontal transfer, These ipi genes encode predicted proteins that are similar to adhesins and invasins from prokaryotic and eukaryotic pathogens (Escherichia coli [tia], Plasmodium falciparum [PfEMP1]) and have coopted the PhoPQ regulatory circuitry of Salmonella virulence genes. Examination of the in vivo induction profile indicates (i) many ivi genes encode regulatory functions (e.g., phoPQ and pmrAB) that serve to enhance the sensitivity and amplitude of virulence gene expression (e.g., spvB); (ii) the biochemical function of many metabolic genes may not represent their sole contribution to virulence; (iii) the host ecology can be inferred from the biochemical functions of ipi genes; and (iv) nutrient limitation plays a dual signaling role in pathogenesis: to induce metabolic functions that complement host nutritional deficiencies and to induce virulence functions required for immediate survival and spread to subsequent host sites.