ANÁLISES GENÔMICAS DE CEPAS ATOXIGÊNICAS DE CORYNEBACTERIUM DIPHTHERIAE ISOLADAS DE LESÕES CUTÂNEAS NO BRASIL

Introdução: A difteria, uma doença aguda e potencialmente fatal, é causada principalmente pelo Corynebacterium diphtheriae e os principais sinais e sintomas decorrem dos efeitos da toxina diftérica (TD), produzida pelo microrganismo quando portador do gene tox. Classicamente, são diferenciados quatro biovares: Gravis, Mitis, Intermedius e Belfanti. Nas últimas décadas, cepas atoxigênicas têm sido isoladas de infecções diversas, sendo considerados patógenos emergentes em potencial, capazes de causar doenças graves e não evitáveis por vacina. Adicionalmente, como o isolamento delas não é de notificação compulsória, são escassos os dados epidemiológicos destas infecções no Brasil e ainda há poucos estudos sobre a resistência antimicrobiana destes isolados. Objetivo: Analisar os genomas completos de cepas de C. diphtheriae (n = 5) isoladas de lesões cutâneas no Brasil entre os anos de 2020 e 2022. Métodos: O sequenciamento foi realizado pela plataforma MiSeq Illumina, o genoma montado de novo pelo software CLC Genomics Workbench e submetido às análises: rMLST e MLST para a confirmação da espécie e Sequência Tipo (ST), respectivamente, e ResFinder para detecção de genes de resistência. As árvores filogenéticas construídas utilizando o programa MEGA versão 11. O método selecionado foi o Neighbor-Joining e a distância inferida foi calculada usando o modelo de Kimura-2 parâmetros. A robustez das topologias foi realizada através da análise de bootstrap (1.000 réplicas). Resultados: Os genomas apresentaram tamanho médio de 2,4 Mb e conteúdo de GC de 53,5%. As análises confirmaram a identificação das cepas como C. diphtheriae tox-. Foram encontrados dois STs conhecidos e mais três novos. Alguns genes de resistência também foram encontrados (cmx, sul1, tet(33) e tetW). Conclusão: Os dados genômicos de cepas atoxigênicas de C. diphtheriae em circulação no Brasil pode contribuir para o monitoramento da emergência e disseminação de clones virulentos e resistentes a agentes antimicrobianos

Transmission of Escherichia coli Causing Pyometra between Two Female Dogs

Despite its clinical relevance, the pathogenesis of canine pyometra remains poorly understood. To date, it is recognized as a non-transmissible infectious disease. In this study, the simultaneous occurrence of pyometra and Escherichia coli in two cohabitant female dogs underwent in-depth investigation due to the hypothesis of transmission between these animals. Two 5-year-old Chow Chow dogs (namely, dogs 23 and 24—D23 and D24) were referred to a veterinary hospital with suspected pyometra. Both animals showed prostration, anorexia, and purulent vulvar discharge over a 1-week period. After ovariohysterectomy, uterine tissue, uterine contents, and rectal swabs were collected for histopathological and microbiological analysis. Uterine histology demonstrated purulent material and multifocal necrosis with endometrial ulceration, and a morphological diagnosis of pyometra was confirmed. Furthermore, E. coli from the same phylogroup (B2) and positive for the same virulence factors with the same antimicrobial susceptibility profile was isolated from the uterine contents of both dogs and the rectum of D23. Conversely, the E. coli strains recovered from D24 differed in phylogroup (one isolate), virulence factors (all three isolates), and antimicrobial susceptibility (all three isolates). Enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) suggested that all isolates from the uterine content of both dogs and the rectal swab of D23 were 100% the same, but different from all isolates in the rectal swab of D24. One isolate from the uterine content of each animal as well as rectal swabs were subjected to whole-genome sequencing (WGS). Both whole-genome multilocus sequence typing(wgMLST) and single-nucleotide polymorphism (SNP) analysis supported the hypothesis that the isolates from the uterine content of both animals and the rectal swab of D23 were clonal. Taken together, these clinical features, pathology, microbiology, and molecular findings suggest, to the best of our knowledge, the first transmission of E. coli associated with pyometra between two animals. These results could impact the management of sites where several females cohabit in the same local area such as kennels

Neuroinformatics Insights towards Multiple Neurosyphilis Complications

Treponema pallidum subspecies pallidum causes syphilis, a sexually transmitted disease that infects more than 2.1 million pregnant women every year. Due to its maximum death rates and augmented risk of human immunodeficiency virus (HIV) infection, the disease is still a matter of debate in many low- and high-income countries. The infection has three stages that lead to several complications if left untreated and can lead to many tertiary complications in the brain, eyes, ears, heart, and pregnancy. Neurosyphilis is also known as the clinical result of infection of the central nervous system by Treponema pallidum subspecies pallidum. It can evolve at any time and from any stage of syphilis exposure. This review briefly explains the severe and multiple neurosyphilitic complications and recently identified cases related to neurosyphilis. We also explained computational neuroscience, neuroinformatics, and in silico models and techniques based on artificial intelligence and other computational and mathematical methods. These techniques have already been applied to several neurological and psychological brain complications and can be applied to neurosyphilis to better understand the persistence of the disease related to the brain that causes neurosyphilis

Bacteriocin Producing Streptococcus agalactiae Strains Isolated from Bovine Mastitis in Brazil

Antibiotic resistance is one of the biggest health challenges of our time. We are now facing a post-antibiotic era in which microbial infections, currently treatable, could become fatal. In this scenario, antimicrobial peptides such as bacteriocins represent an alternative solution to traditional antibiotics because they are produced by many organisms and can inhibit bacteria, fungi, and/or viruses. Herein, we assessed the antimicrobial activity and biotechnological potential of 54 Streptococcus agalactiae strains isolated from bovine mastitis. Deferred plate antagonism assays revealed an inhibition spectrum focused on species of the genus Streptococcus—namely, S. pyogenes, S. agalactiae, S. porcinus, and S. uberis. Three genomes were successfully sequenced, allowing for their taxonomic confirmation via a multilocus sequence analysis (MLSA). Virulence potential and antibiotic resistance assessments showed that strain LGMAI_St_08 is slightly more pathogenic than the others. Moreover, the mreA gene was identified in the three strains. This gene is associated with resistance against erythromycin, azithromycin, and spiramycin. Assessments for secondary metabolites and antimicrobial peptides detected the bacteriocin zoocin A. Finally, comparative genomics evidenced high similarity among the genomes, with more significant similarity between the LGMAI_St_11 and LGMAI_St_14 strains. Thus, the current study shows promising antimicrobial and biotechnological potential for the Streptococcus agalactiae strains

Unraveling the Secrets of a Double-Life Fungus by Genomics: <i>Ophiocordyceps australis</i> CCMB661 Displays Molecular Machinery for Both Parasitic and Endophytic Lifestyles

Ophiocordyceps australis (Ascomycota, Hypocreales, Ophiocordycipitaceae) is a classic entomopathogenic fungus that parasitizes ants (Hymenoptera, Ponerinae, Ponerini). Nonetheless, according to our results, this fungal species also exhibits a complete set of genes coding for plant cell wall degrading Carbohydrate-Active enZymes (CAZymes), enabling a full endophytic stage and, consequently, its dual ability to both parasitize insects and live inside plant tissue. The main objective of our study was the sequencing and full characterization of the genome of the fungal strain of O. australis (CCMB661) and its predicted secretome. The assembled genome had a total length of 30.31 Mb, N50 of 92.624 bp, GC content of 46.36%, and 8,043 protein-coding genes, 175 of which encoded CAZymes. In addition, the primary genes encoding proteins and critical enzymes during the infection process and those responsible for the host–pathogen interaction have been identified, including proteases (Pr1, Pr4), aminopeptidases, chitinases (Cht2), adhesins, lectins, lipases, and behavioral manipulators, such as enterotoxins, Protein Tyrosine Phosphatases (PTPs), and Glycoside Hydrolases (GHs). Our findings indicate that the presence of genes coding for Mad2 and GHs in O. australis may facilitate the infection process in plants, suggesting interkingdom colonization. Furthermore, our study elucidated the pathogenicity mechanisms for this Ophiocordyceps species, which still is scarcely studied

Indian food habit & food ingredients may have a role in lowering the severity & high death rate from COVID-19 in Indians: findings from the first nutrigenomic analysis

Background & objectives: During the COVID-19 pandemic, the death rate was reportedly 5-8 fold lower in India which is densely populated as compared to less populated western countries. The aim of this study was to investigate whether dietary habits were associated with the variations in COVID-19 severity and deaths between western and Indian population at the nutrigenomics level. Methods: In this study nutrigenomics approach was applied. Blood transcriptome of severe COVID-19 patients from three western countries (showing high fatality) and two datasets from Indian patients were used. Gene set enrichment analyses were performed for pathways, metabolites, nutrients, etc., and compared for western and Indian samples to identify the food- and nutrient-related factors, which may be associated with COVID-19 severity. Data on the daily consumption of twelve key food components across four countries were collected and a correlation between nutrigenomics analyses and per capita daily dietary intake was investigated. Results: Distinct dietary habits of Indians were observed, which may be associated with low death rate from COVID-19. Increased consumption of red meat, dairy products and processed foods by western populations may increase the severity and death rate by activating cytokine storm-related pathways, intussusceptive angiogenesis, hypercapnia and enhancing blood glucose levels due to high contents of sphingolipids, palmitic acid and byproducts such as CO2 and lipopolysaccharide (LPS). Palmitic acid also induces ACE2 expression and increases the infection rate. Coffee and alcohol that are highly consumed in western countries may increase the severity and death rates from COVID-19 by deregulating blood iron, zinc and triglyceride levels. The components of Indian diets maintain high iron and zinc concentrations in blood and rich fibre in their foods may prevent CO2 and LPS-mediated COVID-19 severity. Regular consumption of tea by Indians maintains high high-density lipoprotein (HDL) and low triglyceride in blood as catechins in tea act as natural atorvastatin. Importantly, regular consumption of turmeric in daily food by Indians maintains strong immunity and curcumin in turmeric may prevent pathways and mechanisms associated with SARS-CoV-2 infection and COVID-19 severity and lowered the death rate. Interpretation & conclusions: Our results suggest that Indian food components suppress cytokine storm and various other severity related pathways of COVID-19 and may have a role in lowering severity and death rates from COVID-19 in India as compared to western populations. However, large multi-centered case-control studies are required to support our current findings