Atypical cyclic di-AMP signaling is essential for Porphyromonas gingivalis growth and regulation of cell envelope homeostasis and virulence.
Atypical cyclic di-AMP signaling is essential for Porphyromonas gingivalis growth and regulation of cell envelope homeostasis and virulence.
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DOI：
10.1038/s41522-022-00316-w
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发表时间：
2022-07-06
影响因子：
9.2
通讯作者：
Seifert, Roland
中科院分区：
文献类型：
--
作者：
Moradali, M. Fata;Ghods, Shirin;Baehre, Heike;Lamont, Richard J.;Scott, David A.;Seifert, Roland
微生物病原体利用以环（二）核苷酸单磷酸作为第二信使的信号系统来提高致病性过程中的适应性。然而，牙龈卟啉单胞菌（一种关键的革兰氏阴性厌氧口腔病原体）中通过第二信使的信号机制仍然未知。在此，我们报道在各种普遍存在的第二信使中，牙龈卟啉单胞菌菌株主要合成双 -（3′,5′） - 环二腺苷酸单磷酸（c - di - AMP），这对其生长和生存至关重要。我们的研究结果表明牙龈卟啉单胞菌中c - di - AMP合成存在一种不寻常的调控方式。牙龈卟啉单胞菌c - di - AMP磷酸二酯酶（PDE）基因（pdepg）正向调控c - di - AMP合成，并且尽管编码具有磷酸二酯酶活性的保守氨基酸基序，但阻止了c - di - AMP浓度的降低。相反，预测的调控基因cdaR与c - di - AMP PDE基因无关，在这种厌氧菌中作为c - di - AMP合成的强效负调控因子。此外，我们的研究结果显示，在利用丙酮酸时，pdepg和cdaR是调节ATP掺入c - di - AMP所必需的，从而导致生物膜形成增强。我们表明c - di - AMP信号的变化改变了细胞包膜的完整性和内稳态，重要的是，改变了脂多糖层的结构和免疫反应性。此外，微生物 - 微生物相互作用以及牙龈卟啉单胞菌的毒力潜能受到c - di - AMP的调节。这些研究首次揭示了牙龈卟啉单胞菌以及可能其他拟杆菌门细菌中第二信使信号机制的情况。此外，我们的研究结果表明c - di - AMP信号促进了口腔微生物群落的适应性以及致病群落的发展。
Microbial pathogens employ signaling systems through cyclic (di-) nucleotide monophosphates serving as second messengers to increase fitness during pathogenesis. However, signaling schemes via second messengers in Porphyromonas gingivalis, a key Gram-negative anaerobic oral pathogen, remain unknown. Here, we report that among various ubiquitous second messengers, P. gingivalis strains predominantly synthesize bis-(3′,5′)-cyclic di-adenosine monophosphate (c-di-AMP), which is essential for their growth and survival. Our findings demonstrate an unusual regulation of c-di-AMP synthesis in P. gingivalis. P. gingivalis c-di-AMP phosphodiesterase (PDE) gene (pdepg) positively regulates c-di-AMP synthesis and impedes a decrease in c-di-AMP concentration despite encoding conserved amino acid motifs for phosphodiesterase activity. Instead, the predicted regulator gene cdaR, unrelated to the c-di-AMP PDE genes, serves as a potent negative regulator of c-di-AMP synthesis in this anaerobe. Further, our findings reveal that pdepg and cdaR are required to regulate the incorporation of ATP into c-di-AMP upon pyruvate utilization, leading to enhanced biofilm formation. We show that shifts in c-di-AMP signaling change the integrity and homeostasis of cell envelope, importantly, the structure and immunoreactivity of the lipopolysaccharide layer. Additionally, microbe–microbe interactions and the virulence potential of P. gingivalis were modulated by c-di-AMP. These studies provide the first glimpse into the scheme of second messenger signaling in P. gingivalis and perhaps other Bacteroidetes. Further, our findings indicate that c-di-AMP signaling promotes the fitness of the residents of the oral cavity and the development of a pathogenic community.
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影响因子：
3.2
作者：
Chen, T;Hosogi, Y;Duncan, MJ
通讯作者：
Duncan, MJ
影响因子：
4.5
作者：
Devaux L;Sleiman D;Mazzuoli MV;Gominet M;Lanotte P;Trieu-Cuot P;Kaminski PA;Firon A
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Firon A
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通讯作者：
Darveau, Richard P.
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7.6
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通讯作者：
Murdoch C
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作者：
Guo Y;Nguyen KA;Potempa J
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