The Borrelia burgdorferi Adenylate Cyclase, CyaB, Is Important for Virulence Factor Production and Mammalian Infection.
The Borrelia burgdorferi Adenylate Cyclase, CyaB, Is Important for Virulence Factor Production and Mammalian Infection.
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DOI：
10.3389/fmicb.2021.676192
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发表时间：
2021
影响因子：
5.2
通讯作者：
Hyde JA
中科院分区：
文献类型：
--
作者：
Ante VM;Farris LC;Saputra EP;Hall AJ;O'Bier NS;Oliva Chávez AS;Marconi RT;Lybecker MC;Hyde JA
莱姆病的病原体伯氏疏螺旋体（Borrelia burgdorferi）穿过蜱媒介和哺乳动物感染的多个阶段之间的截然不同的环境，其需要遗传适应以进行发病机制。疏螺旋体基因表达对启动哺乳动物适应的RpoS调节子的特定环境信号的变化高度响应，但用于直接检测环境线索的机制尚未确定。腺苷酸环化酶产生的第二信使环磷酸腺苷（cAMP）对环境信号（如碳源和pH）有反应，通过改变基因调控来增强病原菌的毒力。B。伯氏螺旋体编码一种单一的非毒素IV类腺苷酸环化酶（bb 0723，cyaB）。本研究探讨了cyaB的表达沿着其对疏螺旋体毒力调节和哺乳动物感染性的影响。与哺乳动物宿主细胞共孵育特异性诱导cyaB表达，而与培养的蜱细胞共孵育未观察到cyaB表达，表明cyaB表达受哺乳动物细胞系特有的细胞因子影响。cyaB的3′端还编码一个小RNA，SR 0623，其方向与bb 0722重叠。cyaB和SR 0623转录本的差异加工可能改变以毒力决定因子调节和感染性的形式影响功能的能力。在5A 4-NP 1和ML 23背景下产生两种独立的cyaB缺失B31菌株，并单独用截断SR 0623的cyaB ORF、具有完整SR 0623的cyaB或具有诱变全长SR 0623的cyaB进行补充，以评价对疏螺旋体毒力因子和感染性的转录和转录后调控的影响。在不存在cyaB的情况下，ospC的表达和产生显著降低，而BosR和DbpA的蛋白水平显著低于亲本菌株。两个独立的cyaB突变体的抗性研究表明，在早期播散性感染的组织定植减少减毒表型。这项工作表明，B。伯氏疏螺旋体利用cyaB和潜在的cAMP作为调节途径来调节疏螺旋体基因表达和蛋白质产生，以促进疏螺旋体在哺乳动物宿主中的毒力和传播。
Borrelia burgdorferi, the causative agent of Lyme disease, traverses through vastly distinct environments between the tick vector and the multiple phases of the mammalian infection that requires genetic adaptation for the progression of pathogenesis. Borrelial gene expression is highly responsive to changes in specific environmental signals that initiate the RpoS regulon for mammalian adaptation, but the mechanism(s) for direct detection of environmental cues has yet to be identified. Secondary messenger cyclic adenosine monophosphate (cAMP) produced by adenylate cyclase is responsive to environmental signals, such as carbon source and pH, in many bacterial pathogens to promote virulence by altering gene regulation. B. burgdorferi encodes a single non-toxin class IV adenylate cyclase (bb0723, cyaB). This study investigates cyaB expression along with its influence on borrelial virulence regulation and mammalian infectivity. Expression of cyaB was specifically induced with co-incubation of mammalian host cells that was not observed with cultivated tick cells suggesting that cyaB expression is influenced by cellular factor(s) unique to mammalian cell lines. The 3′ end of cyaB also encodes a small RNA, SR0623, in the same orientation that overlaps with bb0722. The differential processing of cyaB and SR0623 transcripts may alter the ability to influence function in the form of virulence determinant regulation and infectivity. Two independent cyaB deletion B31 strains were generated in 5A4-NP1 and ML23 backgrounds and complemented with the cyaB ORF alone that truncates SR0623, cyaB with intact SR0623, or cyaB with a mutagenized full-length SR0623 to evaluate the influence on transcriptional and posttranscriptional regulation of borrelial virulence factors and infectivity. In the absence of cyaB, the expression and production of ospC was significantly reduced, while the protein levels for BosR and DbpA were substantially lower than parental strains. Infectivity studies with both independent cyaB mutants demonstrated an attenuated phenotype with reduced colonization of tissues during early disseminated infection. This work suggests that B. burgdorferi utilizes cyaB and potentially cAMP as a regulatory pathway to modulate borrelial gene expression and protein production to promote borrelial virulence and dissemination in the mammalian host.
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影响因子：
4.1
作者：
Bilusic I;Popitsch N;Rescheneder P;Schroeder R;Lybecker M
通讯作者：
Lybecker M
影响因子：
5.7
作者：
Drecktrah D;Hall LS;Rescheneder P;Lybecker M;Samuels DS
通讯作者：
Samuels DS
影响因子：
3.2
作者：
Caimano, MJ;Eggers, CH;Radolf, JD
通讯作者：
Radolf, JD
影响因子：
4.4
作者：
Blevins, Jon S.;Revel, Andrew T.;Norgard, Michael V.
通讯作者：
Norgard, Michael V.
影响因子：
3.1
作者：
Caimano, Melissa J.;Dunham-Ems, Star;Radolf, Justin D.
通讯作者：
Radolf, Justin D.