Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm Universitygrid.10548.38, Stockholm, Sweden.
School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surreygrid.5475.3, Guildford, United Kingdom.
Infect Immun. 2021 Sep 16;89(10):e0029621. doi: 10.1128/IAI.00296-21. Epub 2021 Jun 14.
Neisseria meningitidis is the etiologic agent of meningococcal meningitis and sepsis. Initial colonization of meningococci in the upper respiratory tract epithelium is crucial for disease development. The colonization occurs in several steps and expression of type IV pili (Tfp) is essential for both attachment and microcolony formation of encapsulated bacteria. Previously, we have shown that host-derived lactate induces synchronized dispersal of meningococcal microcolonies. In this study, we demonstrated that lactate-induced dispersal is dependent on bacterial concentration but not on the quorum-sensing system autoinducer-2 or the two-component systems NarP/NarQ, PilR/PilS, NtrY/NtrX, and MisR/MisS. Further, there were no changes in expression of genes related to assembly, elongation, retraction, and modification of Tfp throughout the time course of lactate induction. By using and mutants, however, we found that lactate-induced dispersal was dependent on PilT retraction but not on phosphoglycerol modification of Tfp even though the PptB activity was important for preventing reaggregation postdispersal. Furthermore, protein synthesis was required for lactate-induced dispersal. Finally, we found that at a lower temperature, lactate-induced dispersal was delayed and unsynchronized, and bacteria reformed microcolonies. We conclude that lactate-induced microcolony dispersal is dependent on bacterial concentration, PilT-dependent Tfp retraction, and protein synthesis and is influenced by environmental temperature.
脑膜炎奈瑟菌是脑膜炎奈瑟菌病和败血症的病原体。脑膜炎奈瑟菌在上呼吸道上皮细胞的初始定植对于疾病的发展至关重要。定植发生在几个步骤中，并且 IV 型菌毛（Tfp）的表达对于荚膜细菌的附着和微菌落形成都是必不可少的。先前，我们已经表明，宿主来源的乳酸诱导脑膜炎奈瑟菌微菌落的同步分散。在这项研究中，我们证明了乳酸诱导的分散依赖于细菌浓度，而不依赖于群体感应系统自诱导物-2 或双组分系统 NarP/NarQ、PilR/PilS、NtrY/NtrX 和 MisR/MisS。此外，在乳酸诱导的整个时间过程中，与 Tfp 的组装、伸长、缩回和修饰相关的基因表达没有变化。然而，通过使用 和 突变体，我们发现乳酸诱导的分散依赖于 PilT 的缩回，而不依赖于 Tfp 的磷酸甘油修饰，尽管 PptB 活性对于防止分散后再聚集很重要。此外，蛋白质合成是乳酸诱导的分散所必需的。最后，我们发现，在较低的温度下，乳酸诱导的分散被延迟且不同步，细菌重新形成微菌落。我们得出结论，乳酸诱导的微菌落分散依赖于细菌浓度、依赖于 PilT 的 Tfp 缩回以及蛋白质合成，并受环境温度的影响。
