Antimicrobial Compounds from Skin Secretions of Species That Belong to the Bufonidae Family.

Skin secretions of toads are a complex mixture of molecules. The substances secreted comprise more than 80 different compounds that show diverse pharmacological activities. The compounds secreted through skin pores and parotid glands are of particular interest because they help toads to endure in habitats full of pathogenic microbes, i.e., bacteria, fungi, viruses, and protozoa, due to their content of components such as bufadienolides, alkaloids, and antimicrobial peptides. We carried out an extensive literature review of relevant articles published until November 2022 in ACS Publications, Google Scholar, PubMed, and ScienceDirect. It was centered on research addressing the biological characterization of the compounds identified in the species of genera Atelopus, Bufo, Duttaphrynus, Melanophryniscus, Peltopryne, Phrynoidis, Rhaebo, and Rhinella, with antibacterial, antifungal, antiviral, and antiparasitic activities; as well as studies performed with analogous compounds and skin secretions of toads that also showed these activities. This review shows that the compounds in the secretions of toads could be candidates for new drugs to treat infectious diseases or be used to develop new molecules with better properties from existing ones. Some compounds in this review showed activity against microorganisms of medical interest such as Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Coronavirus varieties, HIV, Trypanosoma cruzi, Leishmania chagasi, Plasmodium falciparum, and against different kinds of fungi that affect plants of economic interest.

Mining for novel cyclomaltodextrin glucanotransferases unravels the carbohydrate metabolism pathway via cyclodextrins in Thermoanaerobacterales.

Carbohydrate metabolism via cyclodextrins (CM-CD) is an uncommon starch-converting pathway that thoroughly depends on extracellular cyclomaltodextrin glucanotransferases (CGTases) to transform the surrounding starch substrate to α-(1,4)-linked oligosaccharides and cyclodextrins (CDs). The CM-CD pathway has emerged as a convenient microbial adaptation to thrive under extreme temperatures, as CDs are functional amphipathic toroids with higher heat-resistant values than linear dextrins. Nevertheless, although the CM-CD pathway has been described in a few mesophilic bacteria and archaea, it remains obscure in extremely thermophilic prokaryotes (Topt ≥ 70 °C). Here, a new monophyletic group of CGTases with an exceptional three-domain ABC architecture was detected by (meta)genome mining of extremely thermophilic Thermoanaerobacterales living in a wide variety of hot starch-poor environments on Earth. Functional studies of a representative member, CldA, showed a maximum activity in a thermoacidophilic range (pH 4.0 and 80 °C) with remarkable product diversification that yielded a mixture of α:ß:γ-CDs (34:62:4) from soluble starch, as well as G3-G7 linear dextrins and fermentable sugars as the primary products. Together, comparative genomics and predictive functional analysis, combined with data of the functionally characterized key proteins of the gene clusters encoding CGTases, revealed the CM-CD pathway in Thermoanaerobacterales and showed that it is involved in the synthesis, transportation, degradation, and metabolic assimilation of CDs.

Beta-naphthoflavone represses dystrophin Dp71 expression in hepatic cells.

Dystrophin Dp71 is expressed in hepatic tissue; however, its function in this tissue remains unknown. The Dp71 promoter sequence contains conserved CACGC motifs, which constitute the invariant core sequence of xenobiotic-regulatory elements. These elements function as target sites for the aryl hydrocarbon receptor/aryl hydrocarbon nuclear translocator (Ahr/ARNT) in genes regulated by this transcription factor. Thus, Dp71 expression in hepatic cells would be regulated by Ahr signaling. In this study, the effect of the xenobiotics beta-Naphthoflavone (betaNF), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and Benzo[a]Pyrene (BaP) on Dp71 expression was analyzed in Hepa-1 cells. It was demonstrated that betaNF, but not BaP or TCDD, represses Dp71 expression at both transcriptional and translational levels. To test directly the involvement of the Ahr signaling in the negative regulation of Dp71, we analyzed the effect of betaNF on Dp71 expression in the liver of wild type (Ahr+/+) and AHR-null (Ahr-/-) mice. The Dp71 mRNA repression, caused by the betaNF treatment, was also found in the liver tissue of wild type mice; however, such negative effect was reversed in the liver of AHR-null mice, which supports the participation of the Ahr signaling in Dp71 downregulation. Modulation of Dp71 expression by betaNF may represent a novel mechanism of Ahr action.