Prospecção de agrupamentos gênicos conservados associados à síntese de metabólitos secundários em fungos entomopatogênicos

Os fungos entomopatogênicos são importantes patógenos naturais de artrópodes, desempenhando um papel essencial no controle de diversas populaçãos destes animais. O potencial destes fungos como agentes de controle biológico têm sido amplamente explorado. O ciclo de infecção destes organismos é dependente de uma grande diversidade de determinantes de virulência, sendo que a grande maioria dos determinantes de virulência já caracterizados para estas espécies é de origem proteica. Entretanto, uma grande diversidade de metabólitos secundários, moléculas de baixo peso molecular com potencial bioativo, podem também ter participação neste processo. Apesar da sua importância, poucos metabólitos secundários com potencial inseticida já foram relatados e caracterizados. Nesse trabalho, realizamos uma análise de genômica comparativa com o objetivo de identificar agrupamentos gênicos responsáveis pela biossíntese de metabólitos secundários no genoma de 37 espécies de fungos entomopatogênicos da ordem Hypocreales. Notavelmente, as espécies investigadas apresentam uma grande diversidade de genes envolvidos na biossíntese destes compostos, a qual, potencialmente, propícia um perfil metabólico único, o que pode ser um reflexo das distintas estratégias de adaptação observadas nessas espécies. Além disso, alguns agrupamentos gênicos identificados estão presentes na grande maioria das espécies avaliadas, o que indica que esses compostos têm um papel importante nos diferentes estilos de vida desses fungos e podem produzir compostos importantes para a manutenção do ciclo de vida e infecção desses fungos. Considerando que alguns aprupamentos são conservados entre a maioria das 37 espécies de fungos entomopatogênicos da ordem Hypocreales eles podem representar uma fonte de moléculas importantes para aplicação no desenvolvimento de novos inseticidas e, portanto, sua melhor investigação pode auxiliar em implementações mais eficazes do controle biológico.Entomopathogenic fungi are natural pathogens of arthropods, playing an important role in controlling insect populations. Their use as biological control agents has been widely explored. The infectious process is dependent on several virulence determinants and most virulence determinants already characterized for these species are proteins. However, a great diversity of secondary metabolites, bioactive low molecular mass molecules, may also have a role in this process. Despite its importance, few entomopathogenic-derived secondary metabolites harboring insecticidal activity have been reported and characterized. In this work, we performed a comparative genomic analysis of biosynthesis gene clusters, potentially involved in the synthesis of secondary metabolites, in the genome of 37 species of entomopathogenic fungi from Hypocreales order. Notably, the species investigated have a great diversity of genes involved in the biosynthesis of these compounds, which, potentially, provides a unique metabolic profile. This different profile may be the result of the different adaptation strategies observed in these species. In addition, some biosynthetic gene clusters were found conserved in several investigated species, which indicates that the potential compounds could have an important role in the maintenance of the life cycle and infection of these fungi. Furthermore, these conserved BGCs may represent a source of important molecules for application in the insecticidal development. Thus, these genes are interesting targets for future studies and can assist in more effective implementations of biological control strategies

Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly

Zika virus (ZIKV) causes Congenital Zika Syndrome (CZS) in individuals exposed prenatally. Here, we investigated polymorphisms in VEGFA, PTGS2, NOS3, TNF, and NOS2 genes as risk factors to CZS. Forty children with CZS and forty-eight children who were in utero exposed to ZIKV infection, but born without congenital anomalies, were evaluated. Children with CZS were predominantly infected by ZIKV in the first trimester (p < 0.001) and had mothers with lower educational level (p < 0.001) and family income (p < 0.001). We found higher risk of CZS due the allele rs2297518[A] of NOS2 (OR = 2.28, CI 95% 1.17–4.50, p = 0.015). T allele and TT/CT genotypes of the TNF rs1799724 and haplotypes associated with higher expression of TNF were more prevalent in children with CZS and severe microcephaly (p = 0.029, p = 0.041 and p = 0.030, respectively). Our findings showed higher risk of CZS due ZIKV infection in the first trimester and suggested that polymorphisms in NOS2 and TNF genes affect the risk of CZS and severe microcephaly

Functional polymorphisms in the p53 pathway genes on the genetic susceptibility to zika virus teratogenesis

Congenital Zika Syndrome (CZS) occurs in up to 42% of individuals exposed to ZIKV prenatally. Deregulation in gene expression and protein levels of components of the p53 signaling pathway, such as p53 and MDM2, due to ZIKV infection has been reported. Here, we evaluate functional polymorphisms in genes of the p53 signaling pathway as risk factors to CZS. Forty children born with CZS and forty-eight children exposed to ZIKV, but born without congenital anomalies were included in this study. Gestational and sociodemographic information as well as the genotypic and allelic frequencies of functional polymorphisms in TP53, MDM2, MIR605 and LIF genes were compared between the two groups. We found children with CZS exposed predominantly in the first trimester and controls in the third trimester (p<0.001). Moreover, children with CZS were predominantly from families with a lower socioeconomic level (p=0.008). We did not find a statistically significant association between the investigated polymorphisms and development of CZS; however, by comparing individuals with CZS and lissencephaly or without lissencephaly, we found a significative difference in the allelic frequencies of the TP53 rs1042522, which is associated with a more potent p53-induced apoptosis (p=0.007). Our findings suggest that the TP53 rs1042522 polymorphism should be better investigate as a genetic risk factor for the development of lissencephaly in children with CZS