Expanding the Chemical Space of Aryloxy-naphthoquinones as Potential Anti-chagasic Agents: Synthesis and Trypanosomicidal Activity

In continuation our effort to research the chemical space of aryloxy-naphthoquinones as potential anti-Chagas agents, we synthesized nine derivatives and these compounds were evaluated in vitro against the epimastigote and trypomastigote forms of Mexican strains of Trypanosoma cruzi (T. cruzi). Most of these derivatives are highly active against epimastigote forms (IC50 < 1.0 µM) compared to the reference drug benznidazole (Bzn). Then these were evaluated on trypomastigotes, which is showing better potency results than Bzn for compounds 3b and 3g. In addition, the cytotoxicity of these compounds was determined on the murine macrophage cell line J774. 3b and 3i were the most selective compounds against NINOA trypomastigote and INC-5 epimastigote forms, respectively. Further these compounds also have good oral bioavailability according to theoretical predictions. Finally, we were able to determine optimal substitution patterns using pharmacophoric models. All these results are provided very useful structural information to continue our designing of naphthoquinone derivatives against T. cruzi.

Selection of Beauveria bassiana (Hypocreales: Cordycipitaceae) strains to control Xyleborus affinis (Curculionidae: Scolytinae) females

Background Xyleborus affinis Eichhoff (Coleoptera: Curculionidae) is an ambrosia beetle reported to affect avocado trees (Persea americana Mill.). The use of the entomopathogenic fungus (EPF) Beauveria bassiana (Bals.-Criv.) Vuill. for ambrosia beetle control represents an alternative to insecticides. Methods This study was designed in two stages to select B. bassiana strains with potential to control X. affinis females. In the first stage, 19 B. bassiana Mexican strains from EPF collection, isolated from Coleoptera (CHE-CNRCB, http://www.gob.mx/senasica/documentos/coleccion-de-hongos-entomopatogenos), were tested. Analyses included radial growth rate, conidial yield, spore germination, and germ tube length. Results were analysed by Principal Component Analysis (PCA) to identify clusters within favourable growth phenotypes. For the second stage, 10 selected strains were re-analysed for virulence-related metabolic characteristic, including cell wall-bound cuticle-degrading enzymes–Pr1-like proteases and β-N-acetyl glucosaminidases (NAGase) chitinases, conidial hydrophobicity and monopolar germination parameters. A second PCA analysis was run for those virulence parameters analysed, and upon results strains CHE-CNRCB 44, 171, 431 and 485 were selected and tested against X. affinis females. Females were treated with a 1 × 108 conidia mL−1 suspension (recommended rate), using a Potter Tower. Results All strains showed insecticidal activity, inducing up to 58% mortality; about 30% dead beetles developed aerial mycelia (CHE-CNRCB 485) and the fastest mortality rate was t0 = 1.95 (CHE-CNRCB 44). Conclusion Since all selected strains showed virulence against X. affinis females, results indicated the possibility of selecting B. bassiana strains based on multiple metabolic attributes, as a preliminary test to perform bioassays against order-related target insects.

Whole-Genome Sequencing of Mexican Strains of Anaplasma marginale: An Approach to the Causal Agent of Bovine Anaplasmosis

Anaplasma marginale is the main etiologic agent of bovine anaplasmosis, and it is extensively distributed worldwide. We have previously reported the first genome sequence of a Mexican strain of A. marginale (Mex-01-001-01). In this work, we report the genomic analysis of one strain from Hidalgo (MEX-14-010-01), one from Morelos (MEX-17-017-01), and two strains from Veracruz (MEX-30-184-02 and MEX-30-193-01). We found that the genome average size is 1.16-1.17 Mbp with a GC content close to 49.80%. The genomic comparison reveals that most of the A. marginale genomes are highly conserved and the phylogeny showed that Mexican strains cluster with Brazilian strains. The genomic information contained in the four draft genomes of A. marginale from Mexico will contribute to understanding the molecular landscape of this pathogen.

Decolorization and Detoxification of Synthetic Dyes by Mexican Strains of Trametes sp.

Laccases have attracted a great deal of interest because of their remarkable ability for the degradation of synthetic dyes present in wastewaters. New laccase producing sources with robust operational and functional properties are being continuously explored. In this work, the potential for the decolorization and detoxification of synthetic dyes was evaluated in two Mexican strains of the genus Trametes. The decolorization capacity of Trametes maxima LE130 and Trametes sp. LA1 was tested in solid and liquid media. The phytotoxicity of the degradation products was determined using Raphanus sativus and Pisum sativum seeds. In solid media, both strains showed a higher decolorization capacity (p ≤ 0.05) than Phanerochaete chrysosporium ATCC 24725, which is known to be very efficient in lignin and dye-degradation. They produced laccase as the main ligninolytic enzyme; T. maxima LE130 secreted a single isoform of 43.9 kDa, while Trametes sp. LA1 produced three isoforms of 67.3, 58.6 and 52.7 kDa, respectively. Trametes sp. LA1 culture fluids were capable of decolorizing and detoxifying chemically diverse dyes (anthraquinonic dye Remazol Brilliant Blue R, azoic Reactive Black 5 and triphenylmethane Crystal Violet) without the addition of redox mediators. Therefore, this could be considered as a new laccase source which could be potentially competitive in the bioremediation of dye-containing wastewaters.

Trypanosoma cruzi Mexican Strains Differentially Modulate Surface Markers and Cytokine Production in Bone Marrow-Derived Dendritic Cells from C57BL/6 and BALB/c Mice

Dendritic cells (DCs) are a type of antigen-presenting cells that play an important role in the immune response against Trypanosoma cruzi, the causative agent of Chagas disease. In vitro and in vivo studies have shown that the modulation of these cells by this parasite can directly affect the innate and acquired immune response of the host in order to facilitate its biological cycle and the spreading of the species. Many studies show the mechanisms by which T. cruzi modulates DCs, but the interaction of these cells with the Mexican strains of T. cruzi such as Ninoa and INC5 has not yet been properly investigated. Here, we evaluated whether Ninoa and INC5 strains evaded the immunity of their hosts by modulating the biology and function of murine DCs. The CL-Brener strain was used as the reference strain. Herein, it was demonstrated that Ninoa was more infective toward bone marrow-derived dendritic cells (BMDCs) than INC5 and CL-Brener strains in both BMDCs of BALB/c and C57BL/6 mice. Mexican strains of T. cruzi induced different cytokine patterns. In BMDCs obtained from BALB/c mice, Ninoa strain led to the reduction in IL-6 and increased IL-10 production, while in C57BL/6 mice Ninoa strain considerably increased the productions of TNF-α and IL-10. Also, Ninoa and INC5 differentially modulated BMDC expressions of MHC-II, TLR2, and TLR4 in both BALB/c and C57BL/6 mice compared to Brazilian strain CL-Brener. These results indicate that T. cruzi Mexican strains differentially infect and modulate MHC-II, toll-like receptors, and cytokine production in DCs obtained from C57BL/6 and BALB/c mice, suggesting that these strains have developed particular modulatory strategies to disrupt DCs and, consequently, the host immune responses.

First report of New Clonal groups ST706 and ST1088 from MDR Klebsiella pneumoniae Mexican strains

Multidrug-resistant Klebsiella pneumoniae Mexican strains were characterized for the identification of endemic and pandemic clonal groups. The aims of this study were to know population structure and to identify endemic clonal groups inside K. pneumoniae Mexican strains isolated from clinical sources. We studied 93 isolated strains from three third level hospitals and one family clinic from Mexico City. Identification of the strains was done by conventional microbiological methods and an automated system (Vitek2®). The multidrug-resistant phenotype was confirmed following CLSI recommendations, and the strains were classified as MDR, XDR and PDR. Molecular characterization was done by Multilocus Sequence Typing scheme (rpoB, gapA, mdh, pgi, phoE, infB, y tonB). All strains were isolated from hospitalized patients, the most frequent sources were urine and blood cultures. Population structure of K. pneumoniae was clonal, 30 ST were identified, six of them are commonly found. The Clonal complex ST25, ST36, S5392, ST405 and ST551 were isolated from clinical sources, ST1088 was isolated from surfaces of hospital environment.

Draft Genome Sequence of Anaplasma marginale Strain Mex-01-001-01, a Mexican Strain That Causes Bovine Anaplasmosis

Bovine anaplasmosis is an arthropod-borne hemolytic disease caused by Anaplasma marginale. While only a few Anaplasma marginale strains have been reported, no Mexican strains have been reported.