Diverse regulatory pathways modulate bet hedging of competence induction in epigenetically-differentiated phase variants of Streptococcus pneumoniae.
Diverse regulatory pathways modulate bet hedging of competence induction in epigenetically-differentiated phase variants of Streptococcus pneumoniae.
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DOI：
10.1093/nar/gkad760
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发表时间：
2023-10-27
影响因子：
14.9
通讯作者：
中科院分区：
文献类型：
--
作者：
尽管肺炎链球菌能够获得抗生素耐药性并逃避疫苗诱导的免疫，但肺炎链球菌的转化速度各不相同。RMV7分离株的不同阶段变异体在转化效率和生物膜厚度上有显著差异，其特征是由易位可变限制-修饰(TVR)基因座驱动的甲基化模式改变。当相应的TVR等位基因被引入缺乏该基因座的RMV7衍生体中时，这些差异被复制。RNA-seq鉴定了1型菌毛的差异表达，导致生物膜形成的变异，并抑制了较难转化的突变体RMV7domi的感受态诱导。这部分归因于RMV7domi低表达ManLMN，通过引入N-乙酰氨基葡萄糖促进了感受态的诱导。这种作用被一些蛋白质细菌能力调节机制的类似物所增强。此外，RMV7domi的一个与噬菌体相关的染色体岛相对活跃，它通过增加胁迫反应蛋白ClpP和HrcA的表达来抑制转化。然而，HrcA在另一个变异体中增加了感受性诱导，其效果取决于钙补充和热休克。因此，转化效率的异质性可能反映了它受到影响的不同信号通路。这种监管的复杂性将调整整个人群对同步群体感应信号的反应，以产生协调但随机的押注对冲行为。
Despite enabling Streptococcus pneumoniae to acquire antibiotic resistance and evade vaccine-induced immunity, transformation occurs at variable rates across pneumococci. Phase variants of isolate RMV7, distinguished by altered methylation patterns driven by the translocating variable restriction-modification (tvr) locus, differed significantly in their transformation efficiencies and biofilm thicknesses. These differences were replicated when the corresponding tvr alleles were introduced into an RMV7 derivative lacking the locus. RNA-seq identified differential expression of the type 1 pilus, causing the variation in biofilm formation, and inhibition of competence induction in the less transformable variant, RMV7domi. This was partly attributable to RMV7domi’s lower expression of ManLMN, which promoted competence induction through importing N-acetylglucosamine. This effect was potentiated by analogues of some proteobacterial competence regulatory machinery. Additionally, one of RMV7domi’s phage-related chromosomal island was relatively active, which inhibited transformation by increasing expression of the stress response proteins ClpP and HrcA. However, HrcA increased competence induction in the other variant, with its effects depending on Ca2+ supplementation and heat shock. Hence the heterogeneity in transformation efficiency likely reflects the diverse signalling pathways by which it is affected. This regulatory complexity will modulate population-wide responses to synchronising quorum sensing signals to produce co-ordinated yet stochastic bet hedging behaviour.
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影响因子：
5.4
作者：
Croucher NJ;Hanage WP;Harris SR;McGee L;van der Linden M;de Lencastre H;Sá-Leão R;Song JH;Ko KS;Beall B;Klugman KP;Parkhill J;Tomasz A;Kristinsson KG;Bentley SD
通讯作者：
Bentley SD
影响因子：
4.5
作者：
Acebo, Paloma;Martin-Galiano, Antonio J.;Amblar, Monica
通讯作者：
Amblar, Monica
DOI：
10.1073/pnas.89.5.1626
发表时间：
1992-03-01
影响因子：
11.1
作者：
CHANDLER, MS
通讯作者：
CHANDLER, MS
影响因子：
3.3
作者：
Croucher NJ;Chewapreecha C;Hanage WP;Harris SR;McGee L;van der Linden M;Song JH;Ko KS;de Lencastre H;Turner C;Yang F;Sá-Leão R;Beall B;Klugman KP;Parkhill J;Turner P;Bentley SD
通讯作者：
Bentley SD
影响因子：
4.5
作者：
Croucher NJ;Mitchell AM;Gould KA;Inverarity D;Barquist L;Feltwell T;Fookes MC;Harris SR;Dordel J;Salter SJ;Browall S;Zemlickova H;Parkhill J;Normark S;Henriques-Normark B;Hinds J;Mitchell TJ;Bentley SD
通讯作者：
Bentley SD