scholarly journals The Msn2 Transcription Factor Regulates Acaricidal Virulence in the Fungal Pathogen Beauveria bassiana

Author(s):  
Elen R. Muniz ◽  
Cárita S. Ribeiro-Silva ◽  
Walquíria Arruda ◽  
Nemat O. Keyhani ◽  
Éverton K. K. Fernandes

Beauveria bassiana holds promise as a feasible biological control agent for tick control. The B. bassiana stress–response transcription factor Msn2 is known to contribute to fungal growth, conidiogenesis, stress–response and virulence towards insects; however, little is known concerning whether Msn2 is involved in infection across Arthropoda classes. We evaluated the effects of Msn2 on B. bassiana virulence against Rhipicephalus microplus (Acari, Ixodidae) using wild-type, targeted gene knockout (ΔBbmsn2) and complemented mutant (ΔBbmsn2/Bbmsn2) strains. Reproductive parameters of R. microplus engorged females treated topically or by an intra-hemocoel injection of conidial suspensions were assessed. Treated cuticles of engorged females were analyzed by microscopy, and proteolytic activity of B. bassiana on cuticles was assessed. Topically treated engorged females showed high mean larval hatching (>84%) in control and ΔBbmsn2 treatments, whereas treatment with the wild-type or ΔBbmsn2/Bbmsn2 strains resulted in significantly decreased (lowered egg viability) larval hatching. Percent control of R. microplus topically treated with ΔBbmsn2 was lower than in the groups treated with wild-type (56.1%) or ΔBbmsn2/Bbmsn2 strains. However, no differences on reproductive parameters were detected when R. microplus were treated by intra-hemocoel injection using low (800 conidia/tick) doses for all strains tested; R. microplus injected with high doses of wild-type or mutant strains (106 conidia/tick) died before laying eggs (~48 h after treatment). SEM analyses of B. bassiana infection showed similar conidial germination and formation of pseudo-appressoria on tick cuticle. Histological sections of ticks treated with the wild-type or ΔBbmsn2/Bbmsn2 strains showed fungal penetration through the cuticle, and into the tick interior. Hyphae of ΔBbmsn2, however, did not appear to penetrate or breach the tick exocuticle 120 h after treatment. Protease activity was lower on tick cuticles treated with ΔBbmsn2 than those treated with the wild-type or ΔBbmsn2/Bbmsn2 strains. These data show that loss of the Msn2 transcription factor reduced B. bassiana virulence against R. microplus, but did not interfere with conidial germination, appressoria formation or sporulation on tick cadavers, and plays only a minimal role once the cuticle is breached. Our results indicate that the BbMsn2 transcription factor acts mainly during the fungal penetration process and that decreased protease production may be one mechanism that contributes to the inability of the mutant strain to breach the tick cuticle.

2011 ◽  
Vol 111 (4) ◽  
pp. 1142-1149 ◽  
Author(s):  
Kazuyuki Yasuhara ◽  
Yoshitaka Ohno ◽  
Atsushi Kojima ◽  
Kenji Uehara ◽  
Moroe Beppu ◽  
...  

Effects of heat shock transcription factor 1 (HSF1) gene on the regrowth of atrophied mouse soleus muscles were studied. Both HSF1-null and wild-type mice were subjected to continuous hindlimb suspension for 2 wk followed by 4 wk of ambulation recovery. There was no difference in the magnitude of suspension-related decrease of muscle weight, protein content, and the cross-sectional area of muscle fibers between both types of mice. However, the regrowth of atrophied soleus muscle in HSF1-null mice was slower compared with that in wild-type mice. Lower baseline expression level of HSP25, HSC70, and HSP72 were noted in soleus muscle of HSF1-null mice. Unloading-associated downregulation and reloading-associated upregulation of HSP25 and HSP72 mRNA were observed not only in wild-type mice but also in HSF1-null mice. Reloading-associated upregulation of HSP72 and HSP25 during the regrowth of atrophied muscle was observed in wild-type mice. Minor and delayed upregulation of HSP72 at mRNA and protein levels was also seen in HSF1-null mice. Significant upregulations of HSF2 and HSF4 were observed immediately after the suspension in HSF1-null mice, but not in wild-type mice. Therefore, HSP72 expression in soleus muscle might be regulated by the posttranscriptional level, but not by the stress response. Evidence from this study suggested that the upregulation of HSPs induced by HSF1-associated stress response might play, in part, important roles in the mechanical loading (stress)-associated regrowth of skeletal muscle.


2012 ◽  
Vol 6 ◽  
pp. BBI.S9529
Author(s):  
Mohammad Ohid Ullah ◽  
Michael Müller ◽  
Guido J.E.J. Hooiveld

An effective strategy to elucidate the signal transduction cascades activated by a transcription factor is to compare the transcriptional profiles of wild type and transcription factor knockout models. Many statistical tests have been proposed for analyzing gene expression data, but most tests are based on pair-wise comparisons. Since the analysis of microarrays involves the testing of multiple hypotheses within one study, it is generally accepted that one should control for false positives by the false discovery rate (FDR). However, it has been reported that this may be an inappropriate metric for comparing data across different experiments. Here we propose an approach that addresses the above mentioned problem by the simultaneous testing and integration of the three hypotheses (contrasts) using the cell means ANOVA model. These three contrasts test for the effect of a treatment in wild type, gene knockout, and globally over all experimental groups. We illustrate our approach on microarray experiments that focused on the identification of candidate target genes and biological processes governed by the fatty acid sensing transcription factor PPARα in liver. Compared to the often applied FDR based across experiment comparison, our approach identified a conservative but less noisy set of candidate genes with same sensitivity and specificity. However, our method had the advantage of properly adjusting for multiple testing while integrating data from two experiments, and was driven by biological inference. Taken together, in this study we present a simple, yet efficient strategy to compare differential expression of genes across experiments while controlling for multiple hypothesis testing.


2019 ◽  
Vol 7 (5) ◽  
pp. 131 ◽  
Author(s):  
Shao-Yu Lee ◽  
Hsueh-Fen Chen ◽  
Ying-Chieh Yeh ◽  
Yao-Peng Xue ◽  
Chung-Yu Lan

Candida albicans is a commensal that inhabits the skin and mucous membranes of humans. Because of the increasing immunocompromised population and the limited classes of antifungal drugs available, C. albicans has emerged as an important opportunistic pathogen with high mortality rates. During infection and therapy, C. albicans frequently encounters immune cells and antifungal drugs, many of which exert their antimicrobial activity by inducing the production of reactive oxygen species (ROS). Therefore, antioxidative capacity is important for the survival and pathogenesis of C. albicans. In this study, we characterized the roles of the zinc finger transcription factor Sfp1 in the oxidative stress response against C. albicans. A sfp1-deleted mutant was more resistant to oxidants and macrophage killing than wild-type C. albicans and processed an active oxidative stress response with the phosphorylation of the mitogen-activated protein kinase (MAPK) Hog1 and high CAP1 expression. Moreover, the sfp1-deleted mutant exhibited high expression levels of antioxidant genes in response to oxidative stress, resulting in a higher total antioxidant capacity, glutathione content, and glutathione peroxidase and superoxide dismutase enzyme activity than the wild-type C. albicans. Finally, the sfp1-deleted mutant was resistant to macrophage killing and ROS-generating antifungal drugs. Together, our findings provide a new understanding of the complex regulatory machinery in the C. albicans oxidative stress response.


Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 298
Author(s):  
Nkulu Kabange Rolly ◽  
Bong-Gyu Mun ◽  
Byung-Wook Yun

A large number of hormonal biosynthetic or signaling pathways genes controlling shoot branching are widely known for their roles in regulating plant growth and development, operating in synergetic or antagonistic manner. However, their involvement in abiotic stress response mechanism remains unexplored. Initially, we performed an in silico analysis to identify potential transcription binding sites for the basic leucine zipper 62 transcription factor (bZIP62 TF) in the target branching related genes. The results revealed the presence of cis-regulatory elements specific to two bZIP TFs, AtbZIP18 and AtbZIP69, rather than AtbZIP62. Interestingly, these bZIP TFs were previously proposed to be negatively regulated by the AtbZIP62 TF under salinity in Arabidopsis. Therefore, we investigated the transcriptional regulation of more axillary branching (MAX, strigolactone), PIN-FORMED (PINs, auxin carriers), gibberellic acid (GA)-biosynthetic genes as well as isopentenyltransferase (IPT, cytokinin biosynthesis pathway) genes in response to drought stress in Arabidopsis Col-0 wild type. In addition, in the perspective of exploring the transcriptional interplay of the selected genes with the AtbZIP62, we measured their expression by qPCR in the atbzip62 (lacking the AtbZIP62 gene) background under the same conditions. Our findings revealed that the expression of AtMAX2, AtMAX3, and AtMAX4 was differentially regulated by drought stress between the atbzip62 and Col-0 wild type, but not AtMAX1. Similarly, the transcripts accumulation of AtPIN3 and AtPIN7 (known as auxin efflux carriers), and that of the AtAXR1 showed similar regulation patterns in atbzip62. However, AtPIN1 expression was downregulated in Col-0, but no change was observed in atbzip62. Furthermore, AtIPT5 and AtIPT7 exhibited a differential transcripts accumulation pattern in atbzip62 and Col-0 wild type (WT). In the same way, the expression of the GA biosynthetic genes AtGA2ox1 and AtGA20ox2, and that of AtRGA1 were differentially regulated in atbzip62 compared to the Col-0. Meanwhile, AtGA2ox1 showed a similar expression pattern with Col-0. Therefore, all results suggest PIN, MAX, IPT, and GA-biosynthetic genes, which are differentially regulated by AtbZIP62 transcription factor, as emerging candidate genes that could be involved in drought stress response mechanism in Arabidopsis.


Pneumologie ◽  
2012 ◽  
Vol 66 (11) ◽  
Author(s):  
K Hoehne ◽  
H Eibel ◽  
M Grimm ◽  
M Idzko ◽  
J Müller-Quernheim ◽  
...  

Genetics ◽  
1999 ◽  
Vol 153 (4) ◽  
pp. 1573-1581 ◽  
Author(s):  
Susanna Chou ◽  
Sukalyan Chatterjee ◽  
Mark Lee ◽  
Kevin Struhl

Abstract The general transcription factor IIA (TFIIA) forms a complex with TFIID at the TATA promoter element, and it inhibits the function of several negative regulators of the TATA-binding protein (TBP) subunit of TFIID. Biochemical experiments suggest that TFIIA is important in the response to transcriptional activators because activation domains can interact with TFIIA, increase recruitment of TFIID and TFIIA to the promoter, and promote isomerization of the TFIID-TFIIA-TATA complex. Here, we describe a double-shut-off approach to deplete yeast cells of Toa1, the large subunit of TFIIA, to <1% of the wild-type level. Interestingly, such TFIIA-depleted cells are essentially unaffected for activation by heat shock factor, Ace1, and Gal4-VP16. However, depletion of TFIIA causes a general two- to threefold decrease of transcription from most yeast promoters and a specific cell-cycle arrest at the G2-M boundary. These results indicate that transcriptional activation in vivo can occur in the absence of TFIIA.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Ji Zhang ◽  
Hua Cao

AbstractBased on isocitrate dehydrogenase (IDH) alterations, lower grade glioma (LGG) is divided into IDH mutant and wild type subgroups. However, the further classification of IDH wild type LGG was unclear. Here, IDH wild type LGG patients in The Cancer Genome Atlas and Chinese Glioma Genome Atlas were divided into two sub-clusters using non-negative matrix factorization. IDH wild type LGG patients in sub-cluster2 had prolonged overall survival and low frequency of CDKN2A alterations and low immune infiltrations. Differentially expressed genes in sub-cluster1 were positively correlated with RUNX1 transcription factor. Moreover, IDH wild type LGG patients with higher stromal score or immune score were positively correlated with RUNX1 transcription factor. RUNX1 and its target gene REXO2 were up-regulated in sub-cluster1 and associated with the worse prognosis of IDH wild type LGG. RUNX1 and REXO2 were associated with the higher immune infiltrations. Furthermore, RUNX1 and REXO2 were correlated with the worse prognosis of LGG or glioma. IDH wild type LGG in sub-cluster2 was hyper-methylated. REXO2 hyper-methylation was associated with the favorable prognosis of LGG or glioma. At last, we showed that, age, tumor grade and REXO2 expression were independent prognostic factors in IDH wild type LGG.


Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 767
Author(s):  
Kamar Hamade ◽  
Ophélie Fliniaux ◽  
Jean-Xavier Fontaine ◽  
Roland Molinié ◽  
Elvis Otogo Nnang ◽  
...  

Lignans, phenolic plant secondary metabolites, are derived from the phenylpropanoid biosynthetic pathway. Although, being investigated for their health benefits in terms of antioxidant, antitumor, anti-inflammatory and antiviral properties, the role of these molecules in plants remains incompletely elucidated; a potential role in stress response mechanisms has been, however, proposed. In this study, a non-targeted metabolomic analysis of the roots, stems, and leaves of wild-type and PLR1-RNAi transgenic flax, devoid of (+) secoisolariciresinol diglucoside ((+) SDG)—the main flaxseed lignan, was performed using 1H-NMR and LC-MS, in order to obtain further insight into the involvement of lignan in the response of plant to osmotic stress. Results showed that wild-type and lignan-deficient flax plants have different metabolic responses after being exposed to osmotic stress conditions, but they both showed the capacity to induce an adaptive response to osmotic stress. These findings suggest the indirect involvement of lignans in osmotic stress response.


2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Ian Edward Gentle ◽  
Isabel Moelter ◽  
Mohamed Tarek Badr ◽  
Konstanze Döhner ◽  
Michael Lübbert ◽  
...  

AbstractMutations in the transcription factor C/EBPα are found in ~10% of all acute myeloid leukaemia (AML) cases but the contribution of these mutations to leukemogenesis is incompletely understood. We here use a mouse model of granulocyte progenitors expressing conditionally active HoxB8 to assess the cell biological and molecular activity of C/EBPα-mutations associated with human AML. Both N-terminal truncation and C-terminal AML-associated mutations of C/EBPα substantially altered differentiation of progenitors into mature neutrophils in cell culture. Closer analysis of the C/EBPα-K313-duplication showed expansion and prolonged survival of mutant C/EBPα-expressing granulocytes following adoptive transfer into mice. C/EBPα-protein containing the K313-mutation further showed strongly enhanced transcriptional activity compared with the wild-type protein at certain promoters. Analysis of differentially regulated genes in cells overexpressing C/EBPα-K313 indicates a strong correlation with genes regulated by C/EBPα. Analysis of transcription factor enrichment in the differentially regulated genes indicated a strong reliance of SPI1/PU.1, suggesting that despite reduced DNA binding, C/EBPα-K313 is active in regulating target gene expression and acts largely through a network of other transcription factors. Strikingly, the K313 mutation caused strongly elevated expression of C/EBPα-protein, which could also be seen in primary K313 mutated AML blasts, explaining the enhanced C/EBPα activity in K313-expressing cells.


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