Mucosal Environment Induces Phage Susceptibility in Streptococcus mutans

Pathogenic bacteria are attracted toward mucosa, as it is their way of entry into the body. However, we know surprisingly little about the phage-bacterium interactions in the mucosal environment. Here, we explored the effect of the mucosal environment on growth characteristics and phage-bacterium interactions in Streptococcus mutans, a causative agent of dental caries. We found that although mucin supplementation increased bacterial growth and survival, it decreased S. mutans biofilm formation. More importantly, the presence of mucin had a significant effect on S. mutans phage susceptibility. In two experiments done in Brain Heart Infusion Broth, phage M102 replication was detected only with 0.2% mucin supplementation. In 0.1 × Tryptic Soy Broth, 0.5% mucin supplementation led to a 4-log increase in phage titers compared with the control. These results suggest that the mucosal environment can have a major role in the growth, phage sensitivity, and phage resistance of S. mutans, and underline the importance of understanding the effect of mucosal environment on phage-bacterium interactions

USP18-Based Negative Feedback Control Is Induced by Type I and Type III Interferons and Specifically Inactivates Interferon α Response

Type I interferons (IFN) are cytokines that are rapidly secreted upon microbial infections and regulate all aspects of the immune response. In humans 15 type I IFN subtypes exist, of which IFN α2 and IFN β are used in the clinic for treatment of different pathologies. IFN α2 and IFN β are non redundant in their expression and in their potency to exert specific bioactivities. The more recently identified type III IFNs (3 IFN λ or IL-28/IL-29) bind an unrelated cell-type restricted receptor. Downstream of these two receptor complexes is a shared Jak/Stat pathway. Several mechanisms that contribute to the shut down of the IFN-induced signaling have been described at the molecular level. In particular, it has long been known that type I IFN induces the establishment of a desensitized state. In this work we asked how the IFN-induced desensitization integrates into the network built by the multiple type I IFN subtypes and type III IFNs. We show that priming of cells with either type I IFN or type III IFN interferes with the cell's ability to further respond to all IFN α subtypes. Importantly, primed cells are differentially desensitized in that they retain sensitivity to IFN β. We show that USP18 is necessary and sufficient to induce differential desensitization, by impairing the formation of functional binding sites for IFN α2. Our data highlight a new type of differential between IFNs α and IFN β and underline a cross-talk between type I and type III IFN. This cross-talk could shed light on the reported genetic variation in the IFN λ loci, which has been associated with persistence of hepatitis C virus and patient's response to IFN α2 therapy

Transtorno bipolar em crianças: análise de relato de caso 2018-2023

O transtorno bipolar em crianças é uma realidade clínica que demanda atenção especializada. A compreensão dos sintomas, fatores de risco, prevalência e desafios diagnósticos é fundamental para proporcionar intervenções precoces e adequadas, visando melhorar a qualidade de vida desses jovens e reduzir o impacto a longo prazo dessa condição psiquiátrica. Trata-se de um estudo cujo objetivo foi objetivo revisar relatos de caso publicados entre 2018 e 2023 sobre transtorno bipolar em crianças, identificando o estado da arte desses estudos. Para isso, se realizou uma revisão sistemática de literatura utilizando as bases de dados Medical Literature Analysis and Retrieval System Online (MEDLINE), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e Scientific Electronic Library Online (SCIELO). Com a análise e interpretação qualitativa dos resultados, a principal conclusão deste estudo é que o transtorno bipolar na infância é uma condição complexa, manifestando-se com comportamentos consistentes com o Transtorno de Conduta e sendo influenciado por fatores ambientais, familiares e genéticos. O tratamento eficaz requer uma abordagem multidisciplinar, integrando intervenções farmacológicas e não farmacológicas, personalizadas conforme as necessidades individuais. A supervisão familiar é crucial para a adesão ao tratamento, mas reconhece-se a necessidade contínua de pesquisa para aprimorar as estratégias terapêuticas diante da diversidade de casos

The forgotten tale of Brazilian phage therapy

The use of bacteriophages to treat bacterial infections (known as phage therapy) is considered a possible solution to the antimicrobial resistance crisis. However, phage therapy is not a new concept. The discovery of phages in the early 20th century was closely tied to clinical practice, and phage therapy quickly spread around the world. The use of phage therapy in South America in the previous century is still shrouded in mystery and has been mentioned only briefly in recent scientific literature. Research on Brazilian reference collections of medical texts showed that Brazil was an important, but so far little-known, player of phage therapy, uncovering interesting priority claims and missing pieces of phage therapy history. Of note, there is the widespread use of phages against bacillary dysentery and staphylococcal infections, with José da Costa Cruz from the Oswaldo Cruz Institute (Rio de Janeiro, Brazil) as Brazil's leading expert and pioneer. This Historical Review about historical phage use in Brazil fills the gaps in our knowledge about the so-called golden years of phage therapy, providing information about successful experiences that can be useful against dangerous pathogens in our time.peerReviewe

Mimiviruses and the Human Interferon System: Viral Evasion of Classical Antiviral Activities, But Inhibition By a Novel Interferon-beta Regulated Immunomodulatory Pathway

International audienceIn this review we discuss the role of mimiviruses as potential human pathogens focusing on clinical and evolutionary evidence. We also propose a novel antiviral immunomodulatory pathway controlled by interferon-beta (IFN-beta) and mediated by immune-responsive gene 1 (IRG1) and itaconic acid, its product. Acanthamoeba polyphaga Mimivirus (APMV) was isolated from amoebae in a hospital while investigating a pneumonia outbreak. Mimivirus ubiquity and role as protist pathogens are well understood, and its putative status as a human pathogen has been gaining strength as more evidence is being found. The study of APMV and human cells interaction revealed that the virus is able to evade the IFN system by inhibiting the regulation of interferon-stimulated genes, suggesting that the virus and humans have had host-pathogen interactions. It also has shown that the virus is capable of growing on IFN-alpha 2, but not on IFN-beta-treated cells, hinting at an exclusive IFN-beta antiviral pathway. Our hypothesis based on preliminary data and published articles is that IFN-beta preferentially upregulates IRG1 in human macrophagic cells, which in turn produces itaconic acid. This metabolite links metabolism to antiviral activity by inactivating the virus, in a novel immunomodulatory pathway relevant for APMV infections and probably to other infectious diseases as well

Infection of the central nervous system with dengue virus 3 genotype I causing neurological manifestations in Brazil

Abstract: A case of dengue virus 3 (DENV-3) genotype I infection with neurological manifestations occurred in Belo Horizonte, Minas Gerais in October 2012. The serotype was detected by PCR, and the genotype was assessed by sequencing and phylogenetic analysis of the C-prM region. The virus causing neurological manifestations clustered with other sequences of DENV-3 genotype I. Because neurological manifestations of DENV are possibly misdiagnosed in Brazil, this study serves as an alert of the importance of DENV diagnoses in CNS infections

Basal Activation of Type I Interferons (Alpha2 and Beta) and 2′5′OAS Genes: Insights into Differential Expression Profiles of Interferon System Components in Systemic Sclerosis

Objective. Systemic sclerosis (SSc) is a complex autoimmune disease in which interferons (IFNs) may play an essential role. We hypothesized that type I and III IFNs may be found in increased levels in patients and be responsible for SSc autoimmune status. Methods. Type I and III IFN and ISG basal expression profiles were measured by qPCR using RNA from PBMCs of patients and controls . Results. Type I IFNs are increased in SSc patients, while no induction of type III IFNs was detected. This induction cannot be related to IRF7, since no upregulation of this gene was seen on patients. Of the ISGs tested, 2′5′OAS levels were increased in patients, while 6–16 and MxA levels were not. Conclusions. While there is no indication of type III IFN induction, increased levels of type I IFNs may lead to abnormal regulation of ISGs that can be responsible for immune system alterations described for SSc

CALANGO: A phylogeny-aware comparative genomics tool for discovering quantitative genotype-phenotype associations across species

Living species vary significantly in phenotype and genomic content. Sophisticated statistical methods linking genes with phenotypes within a species have led to breakthroughs in complex genetic diseases and genetic breeding. Despite the abundance of genomic and phenotypic data available for thousands of species, finding genotype-phenotype associations across species is challenging due to the non-independence of species data resulting from common ancestry. To address this, we present CALANGO (comparative analysis with annotation-based genomic components), a phylogeny-aware comparative genomics tool to find homologous regions and biological roles associated with quantitative phenotypes across species. In two case studies, CALANGO identified both known and previously unidentified genotype-phenotype associations. The first study revealed unknown aspects of the ecological interaction between Escherichia coli, its integrated bacteriophages, and the pathogenicity phenotype. The second identified an association between maximum height in angiosperms and the expansion of a reproductive mechanism that prevents inbreeding and increases genetic diversity, with implications for conservation biology and agriculture