Penheiter K L, Mathur N, Giles D, Fahlen T, Jones B D
Department of Microbiology, University of Iowa School of Medicine, Iowa City 52242, USA.
Mol Microbiol. 1997 May;24(4):697-709. doi: 10.1046/j.1365-2958.1997.3741745.x.
Salmonella typhimurium initiates infection of a host by invading M cells of Peyer's patches within the small intestine. The ability of the bacteria to invade mammalian cells has been shown to be regulated by environmental conditions, including oxygen concentrations, osmolarity, and growth phase. We have previously created oxygen-regulated Tn5lacZY S. typhimurium mutants that are defective in invasion. We have now identified the invasion genes disrupted by eight of the transposon insertions. These genes encode transcriptional regulators (hilA and invF), type III secretory components (orgA, invG and spaR) and secreted proteins (invC and invD). Examination of the protein-secretion profiles of the non-invasive mutants indicated that each of the mutants was defective in secretion of between one and six proteins. We have also demonstrated that the loss of tissue culture cell invasiveness corresponds to an inability to invade and destroy M cells of Peyer's patches in a murine ligated loop model. Virulence studies, performed in mice, demonstrated that these defects significantly reduced the ability of the mutants to cause murine typhoid fever by an oral route of infection. Virulence by an intraperitoneal route of infection was unaffected. The data indicate that in vitro invasiveness, invasion-protein secretion, and M-cell invasion are critical indicators of S. typhimurium virulence.
鼠伤寒沙门氏菌通过侵入小肠派尔集合淋巴结的M细胞来引发对宿主的感染。已表明该细菌侵入哺乳动物细胞的能力受环境条件调控，包括氧气浓度、渗透压和生长阶段。我们之前创建了在侵入方面存在缺陷的氧调节Tn5lacZY鼠伤寒沙门氏菌突变体。我们现已鉴定出因八个转座子插入而被破坏的侵入基因。这些基因编码转录调节因子（hilA和invF）、III型分泌成分（orgA、invG和spaR）以及分泌蛋白（invC和invD）。对非侵入性突变体的蛋白质分泌谱的检测表明，每个突变体在一至六种蛋白质的分泌方面存在缺陷。我们还证明，在小鼠结扎肠袢模型中，组织培养细胞侵入性的丧失与无法侵入和破坏派尔集合淋巴结的M细胞相对应。在小鼠身上进行的毒力研究表明，这些缺陷显著降低了突变体通过口服感染途径引发鼠伤寒热的能力。腹腔感染途径的毒力不受影响。数据表明，体外侵入性、侵入蛋白分泌和M细胞侵入是鼠伤寒沙门氏菌毒力的关键指标。
