scholarly journals Fusaricidin Biosynthesis Is Controlled via a KinB-Spo0A-AbrB Signal Pathway in Paenibacillus polymyxa WLY78

2021 ◽  
Author(s):  
Yunlong Li ◽  
Haowei Zhang ◽  
Yongbin Li ◽  
Sanfeng Chen
Keyword(s):  
Regulatory Network ◽  
Paenibacillus Polymyxa ◽  
Signal Pathway ◽  
Transcription Start ◽  
Signaling Mechanism ◽  
Lipopeptide Antibiotics ◽  
Direct Binding ◽  
Regulation Mechanisms ◽  
Complex Regulatory Network ◽  
Open Access Article

Fusaricidins produced by Paenibacillus polymyxa are important lipopeptide antibiotics against fungi. The fusGFEDCBA (fusaricidin biosynthesis) operon is responsible for synthesis of fusaricidins. However, the regulation mechanisms of fusaricidin biosynthesis remain to be fully clarified. In this study, we revealed that fusaricidin production is controlled by a complex regulatory network including KinB-Spo0A-AbrB. Evidence suggested that the regulator AbrB represses the transcription of the fus gene cluster by direct binding to the fus promoter, in which the sequences (5′-AATTTTAAAATAAATTTTGTGATTT-3′) located from −136 to −112 bp relative to the transcription start site is required for this repression. Spo0A binds to the abrB promoter that contains the Spo0A-binding sequences (5′-TGTCGAA-3′, 0A box) and in turn prevents the further transcription of abrB. The decreasing concentration of AbrB allows for the derepression of the fus promoter repressed by AbrB. The genome of P. polymyxa WLY78 contains two orthologs (named Kin1508 and Kin4833) of Bacillus subtilis KinB, but only Kin4833 activates sporulation and fusaricidin production, indicating that this kinase may be involved in phosphorylating Spo0A to initiate sporulation and regulate the abrB transcription. Our results reveal that Kin4833 (KinB), Spo0A, and AbrB are involved in regulation of fusaricidin production and a signaling mechanism that links fusaricidin production and sporulation. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

scholarly journals Repression of Capsule Production by XdrA and CodY inStaphylococcus aureus

2018 ◽  
Vol 200 (18) ◽  
Author(s):  
Mei G. Lei ◽  
Chia Y. Lee
Keyword(s):  
Staphylococcus Aureus ◽  
Regulatory Network ◽  
Promoter Region ◽  
Virulence Genes ◽  
Direct Interaction ◽  
Coding Region ◽  
Content Type ◽  
Capsule Production ◽  
Complex Regulatory Network ◽  
Broad Region

ABSTRACTCapsule is one of many virulence factors produced byStaphylococcus aureus, and its expression is highly regulated. Here, we report the repression of capsule by direct interaction of XdrA and CodY with the capsule promoter region. We found, by footprinting analyses, that XdrA repressed capsule by binding to a broad region that extended from upstream of the −35 region of the promoter to the coding region ofcapA, the first gene of the 16-genecapoperon. Footprinting analyses also revealed that CodY bound to a large region that overlapped extensively with that of XdrA. We found that repression of thecapgenes in thexdrAmutant could be achieved by the overexpression ofcodYbut not vice versa, suggestingcodYis epistatic toxdrA. However, we found XdrA had no effect on CodY expression. These results suggest that XdrA plays a secondary role in capsule regulation by promoting CodY repression of thecapgenes. Oxacillin slightly inducedxdrAexpression and reducedcappromoter activity, but the effect of oxacillin on capsule was not mediated through XdrA.IMPORTANCEStaphylococcus aureusemploys a complex regulatory network to coordinate the expression of various virulence genes to achieve successful infections. How virulence genes are coordinately regulated is still poorly understood. We have been studying capsule regulation as a model system to explore regulatory networking inS. aureus. In this study, we found that XdrA and CodY have broad binding sites that overlap extensively in the capsule promoter region. Our results also suggest that XdrA assists CodY in the repression of capsule. As capsule gene regulation by DNA-binding regulators has not been fully investigated, the results presented here fill an important knowledge gap, thereby further advancing our understanding of the global virulence regulatory network inS. aureus.

scholarly journals MicroRNAs in Vascular Biology

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Munekazu Yamakuchi
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Cardiovascular Diseases ◽  
Regulatory Network ◽  
Molecular Basis ◽  
Vascular Inflammation ◽  
Circulating Mirnas ◽  
Infiltrating Cells ◽  
Complex Regulatory Network ◽  
Made In

Vascular inflammation is an important component of the pathophysiology of cardiovascular diseases, such as hypertension, atherosclerosis, and aneurysms. All vascular cells, including endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and infiltrating cells, such as macrophages, orchestrate a series of pathological events. Despite dramatic improvements in the treatment of atherosclerosis, the molecular basis of vascular inflammation is not well understood. In the last decade, microRNAs (miRNAs) have been revealed as novel regulators of vascular inflammation. Each miRNAs suppresses a set of genes, forming complex regulatory network. This paper provides an overview of current advances that have been made in revealing the roles of miRNAs during vascular inflammation. Recent studies show that miRNAs not only exist inside cells but also circulate in blood. These circulating miRNAs are useful biomarkers for diagnosis of cardiovascular diseases. Furthermore, recent studies demonstrate that circulating miRNAs are delivered into certain recipient cells and act as messengers. These studies suggest that miRNAs provide new therapeutic opportunities.

scholarly journals Control of tissue homeostasis, tumorigenesis, and degeneration by coupled bidirectional bistable switches

2021 ◽  
Vol 17 (11) ◽  
pp. e1009606
Author(s):  
Diego Barra Avila ◽  
Juan R. Melendez-Alvarez ◽  
Xiao-Jun Tian
Keyword(s):  
Regulatory Network ◽  
Physiological State ◽  
Critical Role ◽  
Feedback Loops ◽  
Tissue Homeostasis ◽  
State Transitions ◽  
Stochastic Fluctuations ◽  
The One ◽  
Theoretical Analyses ◽  
Complex Regulatory Network

The Hippo-YAP/TAZ signaling pathway plays a critical role in tissue homeostasis, tumorigenesis, and degeneration disorders. The regulation of YAP/TAZ levels is controlled by a complex regulatory network, where several feedback loops have been identified. However, it remains elusive how these feedback loops contain the YAP/TAZ levels and maintain the system in a healthy physiological state or trap the system in pathological conditions. Here, a mathematical model was developed to represent the YAP/TAZ regulatory network. Through theoretical analyses, three distinct states that designate the one physiological and two pathological outcomes were found. The transition from the physiological state to the two pathological states is mechanistically controlled by coupled bidirectional bistable switches, which are robust to parametric variation and stochastic fluctuations at the molecular level. This work provides a mechanistic understanding of the regulation and dysregulation of YAP/TAZ levels in tissue state transitions.

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