Loss of Meningococcal PilU Delays Microcolony Formation and Attenuates Virulence In Vivo
Loss of Meningococcal PilU Delays Microcolony Formation and Attenuates Virulence In Vivo
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DOI：
10.1128/iai.06354-11
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发表时间：
2012-07-01
影响因子：
3.1
通讯作者：
Jonsson, Ann-Beth
中科院分区：
文献类型：
--
作者：
Eriksson, Jens;Eriksson, Olaspers Sara;Jonsson, Ann-Beth
脑膜炎奈瑟菌是世界范围内败血症和细菌性脑膜炎的主要原因。这种细菌表达IV型皮利（Tfp），其介导重要的毒力性状，如细菌聚集体的形成、宿主细胞粘附、抽搐运动和DNA摄取。脑膜炎球菌PilT蛋白是介导菌毛收缩的六聚体ATP酶。皮鲁蛋白由pilT-皮鲁操纵子产生，并且与PilT具有高度同源性。PilT在Tfp生物学中的功能已被广泛研究，而皮鲁的作用仍然知之甚少。在这里，我们表明，皮鲁突变体延迟宿主上皮细胞上的小菌落形成相比，野生型，表明细菌-细菌的相互作用受到影响。在正常人血清中，皮鲁突变体的存活率高于野生型细菌。然而，在鼠疾病模型中，感染pilT突变体的小鼠表现出显著降低的细菌血细胞计数，并且比感染野生型的小鼠存活率更高。用皮鲁突变体感染小鼠导致较低菌血症的趋势，并且存活率仍显著增加，而不是野生型。总之，这些数据表明，皮鲁促进及时的小菌落形成，并且皮鲁和PilT都是完全细菌毒力所需的。
Neisseria meningitidis is a major cause of sepsis and bacterial meningitis worldwide. This bacterium expresses type IV pili (Tfp), which mediate important virulence traits such as the formation of bacterial aggregates, host cell adhesion, twitching motility, and DNA uptake. The meningococcal PilT protein is a hexameric ATPase that mediates pilus retraction. The PilU protein is produced from the pilT-pilU operon and shares a high degree of homology with PilT. The function of PilT in Tfp biology has been studied extensively, whereas the role of PilU remains poorly understood. Here we show that pilU mutants have delayed microcolony formation on host epithelial cells compared to the wild type, indicating that bacterium-bacterium interactions are affected. In normal human serum, the pilU mutant survived at a higher rate than that for wild-type bacteria. However, in a murine model of disease, mice infected with the pilT mutant demonstrated significantly reduced bacterial blood counts and survived at a higher rate than that for mice infected with the wild type. Infection of mice with the pilU mutant resulted in a trend of lower bacteremia, and still a significant increase in survival, than that of the wild type. In conclusion, these data suggest that PilU promotes timely microcolony formation and that both PilU and PilT are required for full bacterial virulence.