Aballay A, Yorgey P, Ausubel F M
Department of Genetics, Harvard Medical School, and Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Curr Biol. 2000 Nov 30;10(23):1539-42. doi: 10.1016/s0960-9822(00)00830-7.
Genetic analysis of host-pathogen interactions has been hampered by the lack of genetically tractable models of such interactions. We showed previously that the human opportunistic pathogen Pseudomonas aeruginosa kills Caenorhabditis elegans, that P. aeruginosa and C. elegans genes can be identified that affect this killing, and that most of these P. aeruginosa genes are also important for mammalian pathogenesis. Here, we show that Salmonella typhimurium as well as other Salmonella enterica serovars including S. enteritidis and S. dublin can also kill C. elegans. When C. elegans is placed on a lawn of S. typhimurium, the bacteria accumulate in the lumen of the worm intestine and the nematodes die over the course of several days. This killing requires contact with live bacterial cells. The worms die with similar kinetics when placed on a lawn of S. typhimurium for a relatively short time (3-5 hours) before transfer to a lawn of E. coli. After the transfer to E. coli, a high titer of S. typhimurium persists in the C. elegans intestinal lumen for the rest of the worms' life. Furthermore, feeding for 5 hours on a 1:1000 mixture of S. typhimurium and E. coli followed by transfer to 100% E. coli, also led to death after several days. This killing correlated with an increase in the titer of S. typhimurium in the C. elegans lumen, which reached 10,000 bacteria per worm. These data indicate that, in contrast to P. aeruginosa, a small inoculum of S. typhimurium can proliferate in the C. elegans intestine and establish a persistent infection. S. typhimurium mutated in the PhoP/PhoQ signal transduction system caused significantly less killing of C. elegans.
宿主 - 病原体相互作用的遗传分析一直受到缺乏此类相互作用的遗传易处理模型的阻碍。我们之前表明，人类机会致病菌铜绿假单胞菌可杀死秀丽隐杆线虫，能够鉴定出影响这种杀伤作用的铜绿假单胞菌和秀丽隐杆线虫基因，并且这些铜绿假单胞菌基因中的大多数对哺乳动物发病机制也很重要。在此，我们表明鼠伤寒沙门氏菌以及包括肠炎沙门氏菌和都柏林沙门氏菌在内的其他肠炎沙门氏菌血清型也能杀死秀丽隐杆线虫。当秀丽隐杆线虫置于鼠伤寒沙门氏菌菌苔上时，细菌会在虫体肠道腔内积聚，线虫会在几天内死亡。这种杀伤作用需要与活细菌细胞接触。当在转移到大肠杆菌菌苔之前，将线虫置于鼠伤寒沙门氏菌菌苔上相对较短的时间（3 - 5小时），线虫会以相似的动力学死亡。转移到大肠杆菌后，高滴度的鼠伤寒沙门氏菌会在秀丽隐杆线虫肠道腔内持续存在于线虫的余生中。此外，在鼠伤寒沙门氏菌和大肠杆菌1:1000的混合物上喂食5小时，然后转移到100%的大肠杆菌上，几天后也会导致死亡。这种杀伤作用与秀丽隐杆线虫肠道腔内鼠伤寒沙门氏菌滴度的增加相关，达到每条线虫10,000个细菌。这些数据表明，与铜绿假单胞菌不同，少量接种的鼠伤寒沙门氏菌可在秀丽隐杆线虫肠道内增殖并建立持续感染。在PhoP/PhoQ信号转导系统中发生突变的鼠伤寒沙门氏菌对秀丽隐杆线虫的杀伤作用明显减弱。
