Functional analysis of the interdependence between DNA uptake sequence and its cognate ComP receptor during natural transformation in Neisseria species.-猫眼课题宝

DOI：

10.1371/journal.pgen.1004014

发表时间：

2013

期刊：

PLoS genetics

影响因子：

4.5

通讯作者：

中科院分区：

生物学2区

文献类型：

作者：

Berry JL;Cehovin A;McDowell MA;Lea SM;Pelicic V

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868556/?report=classic

自然转化是一种广泛存在的生物学过程，通过这种过程，“有能力的”细菌吸收游离DNA，将其纳入其基因组，并发生遗传改变或“转化”。为了抑制外来DNA的有害转化，几种有能力的物种优先摄取含有特定DUS（DNA摄取序列）水印的自身DNA。我们最近的发现，ComP是长期寻求的DUS受体在奈瑟氏菌物种铺平了道路的DUS-ComP的相互依赖性，这是在这里报道的功能分析。通过消除/调节脑膜炎奈瑟菌中的ComP水平，我们表明在DUS存在下观察到的转化的增强完全依赖于ComP，ComP也控制在DUS不存在下的转化。虽然发现DUS中的外围碱基不太重要，但内部碱基是必不可少的，因为单碱基突变导致与ComP和转化的相互作用显著受损。引人注目的是，发现人类奈瑟氏球菌基因组中天然存在的DUS变体与DUS仅相差一个或两个碱基，对于N.脑膜炎通过显示来自N.当在N.脑膜炎球菌，我们证实了一个类似的机制是由所有奈瑟氏菌物种，以促进转化自己的，或密切相关的DNA。总之，这些发现揭示了新的光的分子事件在自然转化的最早一步，并揭示了一个优雅的机制，调节水平基因转移之间的主管物种共享相同的生态位。自然转化是细菌中广泛存在的生物学特性，使它们能够获得新的基因。在脑膜炎奈瑟菌中，转化产生了惊人的变异性，这显著有助于其作为人类病原体的成功。然而，脑膜炎球菌通过ComP受体特异性识别称为DUS（DNA摄取序列）的基序，优先摄取其自身的DNA，从而保护自身免受外来DNA的不受控制的转化。我们在这里表明，（i）在存在和不存在DUS的情况下，ComP控制脑膜炎球菌的转化，（ii）DUS的一些碱基对于ComP的识别和转化更重要，（iii）其他人类奈瑟氏球菌中的DUS变体对于N.脑膜炎球菌，和（iv）这些细菌中的ComP同源物能够结合它们的同源DUS变体并介导DUS特异性转化。这些发现为自然转化最早阶段的分子事件提供了新的线索。它们还揭示了一种以前未被认识到的机制，该机制可能在帮助居住在“拥挤”环境（如人类鼻咽）中的许多有能力的物种抑制外源DNA的转化并保护物种结构方面发挥关键作用。

Natural transformation is the widespread biological process by which “competent” bacteria take up free DNA, incorporate it into their genomes, and become genetically altered or “transformed”. To curb often deleterious transformation by foreign DNA, several competent species preferentially take up their own DNA that contains specific DUS (DNA uptake sequence) watermarks. Our recent finding that ComP is the long sought DUS receptor in Neisseria species paves the way for the functional analysis of the DUS-ComP interdependence which is reported here. By abolishing/modulating ComP levels in Neisseria meningitidis, we show that the enhancement of transformation seen in the presence of DUS is entirely dependent on ComP, which also controls transformation in the absence of DUS. While peripheral bases in the DUS were found to be less important, inner bases are essential since single base mutations led to dramatically impaired interaction with ComP and transformation. Strikingly, naturally occurring DUS variants in the genomes of human Neisseria commensals differing from DUS by only one or two bases were found to be similarly impaired for transformation of N. meningitidis. By showing that ComPsub from the N. subflava commensal specifically binds its cognate DUS variant and mediates DUS-enhanced transformation when expressed in a comP mutant of N. meningitidis, we confirm that a similar mechanism is used by all Neisseria species to promote transformation by their own, or closely related DNA. Together, these findings shed new light on the molecular events involved in the earliest step in natural transformation, and reveal an elegant mechanism for modulating horizontal gene transfer between competent species sharing the same niche. Natural transformation is a widespread biological property in bacteria which allows them to acquire new genes. In Neisseria meningitidis, transformation generates an astonishing variability which contributes markedly to its success as a human pathogen. However, meningococci protect themselves from uncontrolled transformation by foreign DNA by preferentially taking up their own DNA through specific recognition of motifs known as DUS (DNA uptake sequence) by the ComP receptor. We show here that (i) ComP controls transformation in the meningococcus both in the presence and in the absence of DUS, (ii) some bases of DUS are more important for recognition by ComP and transformation, (iii) DUS variants in other human Neisseria commensals are impaired for transformation of N. meningitidis, and (iv) ComP homologs in these commensals are able to bind their cognate DUS variant and mediate DUS-specific transformation. These findings shed new light on the molecular events involved in the earliest step in natural transformation. They also reveal a previously unrecognized mechanism that is likely to play a key role in helping the many competent species that inhabit a “crowded” environment such as the human nasopharynx to curb transformation by foreign DNA and preserve species structure.