Genetic Basis of Virulence Attenuation Revealed by Comparative Genomic Analysis of Mycobacterium tuberculosis Strain H37Ra versus H37Rv

Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading infectious disease despite the availability of chemotherapy and BCG vaccine. The commonly used avirulent M. tuberculosis strain H37Ra was derived from virulent strain H37 in 1935 but the basis of virulence attenuation has remained obscure despite numerous studies. We determined the complete genomic sequence of H37Ra ATCC25177 and compared that with its virulent counterpart H37Rv and a clinical isolate CDC1551. The H37Ra genome is highly similar to that of H37Rv with respect to gene content and order but is 8,445 bp larger as a result of 53 insertions and 21 deletions in H37Ra relative to H37Rv. Variations in repetitive sequences such as IS6110 and PE/PPE/PE-PGRS family genes are responsible for most of the gross genetic changes. A total of 198 single nucleotide variations (SNVs) that are different between H37Ra and H37Rv were identified, yet 119 of them are identical between H37Ra and CDC1551 and 3 are due to H37Rv strain variation, leaving only 76 H37Ra-specific SNVs that affect only 32 genes. The biological impact of missense mutations in protein coding sequences was analyzed in silico while nucleotide variations in potential promoter regions of several important genes were verified by quantitative RT-PCR. Mutations affecting transcription factors and/or global metabolic regulations related to in vitro survival under aging stress, and mutations affecting cell envelope, primary metabolism, in vivo growth as well as variations in the PE/PPE/PE-PGRS family genes, may underlie the basis of virulence attenuation. These findings have implications not only for improved understanding of pathogenesis of M. tuberculosis but also for development of new vaccines and new therapeutic agents

Identification of SARS-CoV-2 Main Protease Inhibitors Using Chemical Similarity Analysis Combined with Machine Learning

SARS-CoV-2 Main Protease (Mpro) is an enzyme that cleaves viral polyproteins translated from the viral genome, which is critical for viral replication. Mpro is a target for anti-SARS-CoV-2 drug development. Herein, we performed a large-scale virtual screening by comparing multiple structural descriptors of reference molecules with reported anti-coronavirus activity against a library with >17 million compounds. Further filtering, performed by applying two machine learning algorithms, identified eighteen computational hits as anti-SARS-CoV-2 compounds with high structural diversity and drug-like properties. The activities of twelve compounds on Mpro’s enzymatic activity were evaluated by fluorescence resonance energy transfer (FRET) assays. Compound 13 (ZINC13878776) significantly inhibited SARS-CoV-2 Mpro activity and was employed as a reference for an experimentally hit expansion. The structural analogues 13a (ZINC4248385), 13b (ZNC13523222), and 13c (ZINC4248365) were tested as Mpro inhibitors, reducing the enzymatic activity of recombinant Mpro with potency as follows: 13c > 13 > 13b > 13a. Then, their anti-SARS-CoV-2 activities were evaluated in plaque reduction assays using Vero CCL81 cells. Subtoxic concentrations of compounds 13a, 13c, and 13b displayed in vitro antiviral activity with IC50 in the mid micromolar range. Compounds 13a–c could become lead compounds for the development of new Mpro inhibitors with improved activity against anti-SARS-CoV-2

Antibody responses to influenza viruses in paediatric patients and their contacts at the onset of the 2009 pandemic in Mexico

Introduction: On April 2009, the Mexican Ministry of Health received notification of cases of severe pneumonia mostly affecting young healthy people; this was the beginning of the first influenza pandemic of the 21st century. The nature of the immune response to the influenza A(H1N1)2009 pandemic strain in Mexico at the beginning of the pandemic outbreak has not been completely defined. We describe the serological response to the 2009 pandemic influenza virus in paediatric patients with influenza-like illness, their household contacts (HHCs), and exposed health-care workers (HCWs) at the beginning of the pandemic outbreak in Mexico City. Methodology: thirty pre-epidemic and 129 epidemic samples were collected and serum antibodies were measured against A(H1N1)2009 pandemic virus and two non-pandemic swine influenza viruses by an haemagglutination inhibition assay. Results: 91% (29/32) of the convalescence samples from confirmed patients had an antibody titre ≥ 10 (GMT 25), 63% (41/65) of the HHCs (GMT 12), 41% of HCWs (GMT 6) and 13% (4/30) of pre-epidemic samples (GMT 6) for the pandemic influenza virus. Of the 32 confirmed cases, 60% had an antibody titre ≥ 40 for the pandemic strain, 53% for the A/swine/Iowa(H1N1) virus (GMT 62) and 43% for the A/swine/Texas(H3N2) virus (GMT 66). Conclusion: The antibody response to 2009 pandemic influenza virus was widespread in convalescence samples from patients with confirmed pandemic influenza infection but the GMT was below the protective titre. There was no evidence that antibodies to the swine influenza viruses had cross-protective effect against the 2009 pandemic influenza virus.</p

Co-stimulatory signals increase the reactivity of γδ T cells towards mycobacterial antigens

Although it has been shown that γδ T lymphocytes are able to react with different cell-associated or soluble antigens, the immune repertoire of these cells appears to be skewed to the recognition of mycobacterial antigens. We have studied the number and reactivity of γδ T cells towards several mycobacterial antigens in patients with tuberculosis and leprosy, as well as their healthy contacts and control individuals. We found an increased number of Vδ2+ cells in healthy contacts (PPD+ and lepromin+) and tuberculoid leprosy patients. The γδ T cells from lepromatous leprosy showed a decreased response to all antigens tested, but some of these patients exhibited a significant response to the 30-kD glycoprotein of Mycobacterium tuberculosis. Interestingly, the reactivity of γδ T cells against mycobacterial antigens was significantly increased by costimulatory signals generated through CD7, LFA-1, CD50 and CD69 in all groups. However, signalling through CD69 did not enhance the responsiveness of γδ lymphocytes from lepromatous patients. On the other hand, the in vitro blockade of IL-10 with a specific antibody enhanced the cell proliferation of γδ lymphocytes from lepromatous leprosy patients, whereas exogenous IL-10 had an opposite effect in most individuals studied. These results suggest the potential role of different cell membrane receptors in the regulation of γδ T cell proliferation induced by mycobacteria, as well as the possible involvement of IL-10 in this phenomenon

Resúmenes de la Primera Jornada del Grupo de Catálisis de la Universidad Pedagógica y Tecnológica de Colombia (GC-UPTC)

The conference proceedings of the first meeting on Catalysis of the Pedagogical and Technological University of Colombia are presented. This conference will be allowed in short time to potentiate the social appropriation of knowledge in this area of science at the regional level, providing opportunities for participants to present their work, and facilitating the dissemination of scientific knowledge.Se presentan los resúmenes de la primera Jornada de Catálisis de la Universidad Pedagógica y Tecnológica de Colombia. Esta conferencia permitirá en poco tiempo potencializar la apropiación social del conocimiento en esta área de la ciencia a nivel regional, brindando oportunidades para que los participantes expongan sus trabajos, y facilitando la difusión del conocimiento científico en esta área

Edible films and coatings based on mango (var. Ataulfo) by-products to improve gas transfer rate of peach

Fruit waste and by-products are economical materials for the development of biodegradable and active packaging. The aims of this study were to develop, characterize and evaluate biodegradable coatings and films by using mango peel and antioxidant extracts of seed kernel. The proximate composition of peel was also determined. Structural, barrier, optical and antioxidant properties were analyzed in the films. Gas transfer rates and the ethylene production in peach were evaluated. Edible films formulated with mango peel showed good barrier properties, with the water vapor permeability varying from 0.88×1010 - 1.00×1010gm1s1 Pa1. The addition of antioxidant extract does not show a significant effect (p>0.05) on optical properties. Furthermore, antioxidant activity and polyphenol content increased by 18% and 60% respectively. Peach coated with a solution of mango peel (1.09%), antioxidant extract of mango seed kernel (0.078gL1) and glycerol (0.33%) showed 64% and 29% less ethylene and CO2 production, respectively, and 39% less O2 consumption when compared with peaches without coating. The reduction in gas transfer ensures the greater extension of the shelf life of fruit treated. By-products of mango may thus be suitable for the production of low-cost biodegradable and active packaging.C.Torres-LeónthankstheMaltaCouncilforScience andTechnology (CONACYT) for his post-graduate scholarship (No. 340301). M. L. Flores-López thanks, CONACYT for the Ph.D. fellowship support (No. 215499/310847) and COECTY-Coahuila State Government (COAH2016-C11-A04). Authors are thankful to engineer Madalena Vieira and toPh.D.JuanCarlosContrerasfortheirvaluablesuggestionsduringthis study.info:eu-repo/semantics/publishedVersio