Role of glucose and CcpA in capsule expression and virulence of Streptococcus suis

Streptococcus suis is one of the most important pathogens in pigs and is also an emerging zoonotic agent. After crossing the epithelial barrier, S. suis causes bacteraemia, resulting in meningitis, endocarditis and bronchopneumonia. Since the host environment seems to be an important regulatory component for virulence, we related expression of virulence determinants of S. suis to glucose availability during growth and to the sugar metabolism regulator catabolite control protein A (CcpA). We found that expression of the virulence-associated genes arcB, representing arcABC operon expression, cps2A, representing capsular locus expression, as well as sly, ofs, sao and epf, differed significantly between exponential and early stationary growth of a highly virulent serotype 2 strain. Deletion of ccpA altered the expression of the surface-associated virulence factors arcB, sao and eno, as well as the two currently proven virulence factors in pigs, ofs and cps2A, in early exponential growth. Global expression analysis using a cDNA expression array revealed 259 differentially expressed genes in early exponential growth, of which 141 were more highly expressed in the CcpA mutant strain 10¿ccpA and 118 were expressed to a lower extent. Interestingly, among the latter genes, 18 could be related to capsule and cell wall synthesis. Correspondingly, electron microscopy characterization of strain 10¿ccpA revealed a markedly reduced thickness of the capsule. This phenotype correlated with enhanced binding to porcine plasma proteins and a reduced resistance to killing by porcine neutrophils. Taken together, our data demonstrate that CcpA has a significant effect on the capsule synthesis and virulence properties of S. suis

ArgR is an essential local transcriptional regulator of the arcABC-operon in Streptococcus suis and crucial for biological fitness in acidic environment

Streptococcus suis is one of the most important pathogens in pigs and can also cause severe infections in humans. Despite its clinical relevance very little is known about the factors contributing to its virulence. Recently, we identified a new putative virulence factor in Streptococcus suis, the arginine deiminase system (ADS), an arginine catabolic enzyme system encoded by the arcABC-operon, which enables Streptococcus suis to survive in acidic environment. In this study, we focused on ArgR, an ADS associated regulator belonging to the ArgR/AhrC arginine repressor family. Using an argR knock-out strain we could show that ArgR is essential for arcABC-operon expression and necessary for the biological fitness of Streptococcus suis. By cDNA expression microarray analyses and quantitative real time RT-PCR we found that the arcABC-operon is the only gene cluster regulated by ArgR, which is in contrast to many other bacteria. Reporter gene analysis with gfp under the control of the arcABC promoter demonstrated that ArgR is able to activate the arcABC promoter. Electrophoretic mobility shift assays with fragments of the arcABC promoter and recombinant ArgR, and chromatin immunoprecipitation with antibodies directed against ArgR revealed that ArgR interacts with the arcABC promoter in vitro and in vivo by binding to a region from -147 to 72 bp upstream of the transcriptional start point. Overall our results show that in Streptococcus suis ArgR is an essential, system specific transcriptional regulator of the ADS directly interacting with the arcABC promoter in vivo

Role of phagocyte extracellular traps during Mycobacterium tuberculosis infections and tuberculosis disease processes.

Mycobacterium tuberculosis (M.tb) infections remain one of the most significant causes of mortality worldwide. The current situation shows an emergence of new antibiotic-resistant strains making it difficult to control the tuberculosis (TB) disease. A large part of its success as a pathogen is due to its ability to persist for years or even decades without causing evident clinical manifestations. M.tb is highly successful in evading the host-defense by manipulating host-signalling pathways. Although macrophages are generally viewed as the key cell type involved in harboring M.tb, growing evidence shows that neutrophils also play a fundamental role. Both cells are known to act in multiple ways when encountering an invading pathogen, including phagocytosis, release of cytokines and chemokines, and oxidative burst. In addition, the formation of neutrophil extracellular traps (NETs) and macrophage extracellular traps (METs) has been described to contribute to M.tb infections. NETs/METs are extracellular DNA fibers with associated granule components, which are released upon activation of the cells by the pathogen or by pro-inflammatory mediators. On one hand, they can lead to a protective immune response by entrapment and killing of pathogens. However, on the other hand, they can also play a severe pathological role by inducing tissue damage. Extracellular traps (ETs) produced in the pulmonary alveoli can expand easily and expose tissue-damaging factors with detrimental effects. Since host-directed therapies offer a complementary strategy in TB, the knowledge of NET/MET formation is important for understanding potential protective versus detrimental pathways during innate immune signaling. In this review, we summarize the progress made in understanding the role of NETs/METs in the pathogenesis of TB

From Euclidean Geometry to Knots and Nets

This document is the Accepted Manuscript of an article accepted for publication in Synthese. Under embargo until 19 September 2018. The final publication is available at Springer via https://doi.org/10.1007/s11229-017-1558-x.This paper assumes the success of arguments against the view that informal mathematical proofs secure rational conviction in virtue of their relations with corresponding formal derivations. This assumption entails a need for an alternative account of the logic of informal mathematical proofs. Following examination of case studies by Manders, De Toffoli and Giardino, Leitgeb, Feferman and others, this paper proposes a framework for analysing those informal proofs that appeal to the perception or modification of diagrams or to the inspection or imaginative manipulation of mental models of mathematical phenomena. Proofs relying on diagrams can be rigorous if (a) it is easy to draw a diagram that shares or otherwise indicates the structure of the mathematical object, (b) the information thus displayed is not metrical and (c) it is possible to put the inferences into systematic mathematical relation with other mathematical inferential practices. Proofs that appeal to mental models can be rigorous if the mental models can be externalised as diagrammatic practice that satisfies these three conditions.Peer reviewe

To Moscow with Love: Partial Reconstruction of Vygotsky’s Trip to London

The Russian psychologist Lev Vygotsky (1896–1934) left the Soviet Union only once to attend a conference on the education of the deaf in London. So far almost nothing was known about this trip, which took place in a period when Vygotsky was still completely unknown as a psychologist, both inside his own country and abroad. Making use of a newly discovered notebook, it proved possible to partially reconstruct Vygotsky’s journey and stay in London. Vygotsky’s very personal remarks show him to have been a very sensitive and spirited man, who was prey to strong emotions during the conference and afterwards. Rather surprisingly, Vygotsky’s own paper about the education of the deaf was never presented during the conference and the stay in London appears to have had a limited value for his own scientific development

Redes Sociais e Comportamento Sexual: para uma visão relacional da sexualidade, do risco e da prevenção

Com base num inquérito representativo da população portuguesa entre 18 e 65 anos, realizado em 2007, este estudo investiga o impacto de fatores de rede social sobre os comportamentos sexuais dos indivíduos. Através da percepção normativa dos inquiridos sobre a moral sexual dos seus amigos e familiares e de indicadores relativos à caracterização da rede de confidência sexual, tais como o número, a identidade, o gênero, a idade e o comportamento dos confidentes em matéria de sexualidade e prevenção face ao risco de infecção por DSTs, obtivemos um retrato multidimensional das redes sociais dos indivíduos. A realização de análises de regressão linear e logística permitiu avaliar o impacto preditivo da rede sobre o número de parceiros sexuais, as relações sexuais ocasionais e o uso do preservativo. Os dados mostram que os fatores de rede são importantes para explicar o comportamento sexual dos indivíduos. Redes constituídas por amigos e mais liberais em termos de moral sexual tendem a influenciar o comportamento sexual, levando a um maior experimentalismo, sobretudo no caso das mulheres. Por outro lado, a homologia entre o comportamento sexual dos confidentes e o dos inquiridos é relevante para explicar o recurso ao preservativo nas relações sexuais ocasionais, especialmente no caso dos homens. Tanto numa perspectiva relacional da sexualidade como numa óptica epidemiológica, a análise das redes sociais dos indivíduos constitui um aspecto importante para a compreensão e explicação da variedade de experiências sexuais, mais restritas ou mais plurais, e para os riscos de infecção que daí podem advir