Evolution of H3N2 Influenza Virus in a Guinea Pig Model

Studies of influenza virus evolution under controlled experimental conditions can provide a better understanding of the consequences of evolutionary processes with and without immunological pressure. Characterization of evolved strains assists in the development of predictive algorithms for both the selection of subtypes represented in the seasonal influenza vaccine and the design of novel immune refocused vaccines. To obtain data on the evolution of influenza in a controlled setting, naïve and immunized Guinea pigs were infected with influenza A/Wyoming/2003 (H3N2). Virus progeny from nasal wash samples were assessed for variation in the dominant and other epitopes by sequencing the hemagglutinin (HA) gene to quantify evolutionary changes. Viral RNA from the nasal washes from infection of naïve and immune animals contained 6% and 24.5% HA variant sequences, respectively. Analysis of mutations relative to antigenic epitopes indicated that adaptive immunity played a key role in virus evolution. HA mutations in immunized animals were associated with loss of glycosylation and changes in charge and hydrophobicity in and near residues within known epitopes. Four regions of HA-1 (75–85, 125–135, 165–170, 225–230) contained residues of highest variability. These sites are adjacent to or within known epitopes and appear to play an important role in antigenic variation. Recognition of the role of these sites during evolution will lead to a better understanding of the nature of evolution which help in the prediction of future strains for selection of seasonal vaccines and the design of novel vaccines intended to stimulated broadened cross-reactive protection to conserved sites outside of dominant epitopes

Enzymatic Mechanisms Involved in Evasion of Fungi to the Oxidative Stress: Focus on Scedosporium apiospermum

The airways of patients with cystic fibrosis (CF) are frequently colonized by various filamentous fungi, mainly Aspergillus fumigatus and Scedosporium species. To establish within the respiratory tract and cause an infection, these opportunistic fungi express pathogenic factors allowing adherence to the host tissues, uptake of extracellular iron, or evasion to the host immune response. During the colonization process, inhaled conidia and the subsequent hyphae are exposed to reactive oxygen species (ROS) and reactive nitrogen species (RNS) released by phagocytic cells, which cause in the fungal cells an oxidative stress and a nitrosative stress, respectively. To cope with these constraints, fungal pathogens have developed various mechanisms that protect the fungus against ROS and RNS, including enzymatic antioxidant systems. In this review, we summarize the different works performed on ROS- and RNS-detoxifying enzymes in fungi commonly encountered in the airways of CF patients and highlight their role in pathogenesis of the airway colonization or respiratory infections. The potential of these enzymes as serodiagnostic tools is also emphasized. In addition, taking advantage of the recent availability of the whole genome sequence of S. apiospermum, we identified the various genes encoding ROS- and RNS-detoxifying enzymes, which pave the way for future investigations on the role of these enzymes in pathogenesis of these emerging species since they may constitute new therapeutics targets

Single gene locus changes perturb complex microbial communities as much as apex predator loss

Many bacterial species are highly social, adaptively shaping their local environment through the production of secreted molecules. This can, in turn, alter interaction strengths among species and modify community composition. However, the relative importance of such behaviours in determining the structure of complex communities is unknown. Here we show that single-locus changes affecting biofilm formation phenotypes in Bacillus subtilis modify community structure to the same extent as loss of an apex predator and even to a greater extent than loss of B. subtilis itself. These results, from experimentally manipulated multitrophic microcosm assemblages, demonstrate that bacterial social traits are key modulators of the structure of their communities. Moreover, they show that intraspecific genetic variability can be as important as strong trophic interactions in determining community dynamics. Microevolution may therefore be as important as species extinctions in shaping the response of microbial communities to environmental change

Bacillus anthracis Spore Surface Protein BclA Mediates Complement Factor H Binding to Spores and Promotes Spore Persistence

Spores of Bacillus anthracis, the causative agent of anthrax, are known to persist in the host lungs for prolonged periods of time, however the underlying mechanism is poorly understood. In this study, we demonstrated that BclA, a major surface protein of B. anthracis spores, mediated direct binding of complement factor H (CFH) to spores. The surface bound CFH retained its regulatory cofactor activity resulting in C3 degradation and inhibition of downstream complement activation. By comparing results from wild type C57BL/6 mice and complement deficient mice, we further showed that BclA significantly contributed to spore persistence in the mouse lungs and dampened antibody responses to spores in a complement C3-dependent manner. In addition, prior exposure to BclA deletion spores (ΔbclA) provided significant protection against lethal challenges by B. anthracis, whereas the isogenic parent spores did not, indicating that BclA may also impair protective immunity. These results describe for the first time an immune inhibition mechanism of B. anthracis mediated by BclA and CFH that promotes spore persistence in vivo. The findings also suggested an important role of complement in persistent infections and thus have broad implications

Politicidade do cuidado e processo de trabalho em saúde: conhecer para cuidar melhor, cuidar para confrontar, cuidar para emancipar Politicity of care and work process in health: knowing to take a better care, taking care to confront, taking care to emancipate

Politicidade do cuidado diz respeito ao manejo disruptivo da relação entre ajuda e poder para construção da autonomia de sujeitos. Tal concepção se expressa principalmente pelo triedro conhecer para cuidar melhor, cuidar para confrontar, cuidar para emancipar, que, em contextos sócio-históricos específicos e adaptado ao processo de trabalho em saúde, pode se constituir numa referência reordenadora de relações de domínio. Trata-se de uma reflexão teórico-filosófica, fundamentada em tese de doutorado, que aprofunda a ambivalência do cuidado, concebido tanto pelo modo de ser solidário, como pelo vir a ser político. Objetiva-se indicar aplicabilidades à concepção de politicidade do cuidado no âmbito do processo de trabalho dos profissionais de saúde, sinalizando potencialidades emancipatórias. A primeira parte faz uma reflexão aprofundada sobre a politicidade do cuidado nas dimensões ontológicas, epistemológicas, biológica e política, argumentando sobre a tensa relação entre ajuda e poder presente no gesto de cuidar. Na segunda, contextualiza-se essa teorização na forma desigual de organizar e produzir cuidados em saúde, discutindo-se a mudança do modelo de atenção à saúde. Na terceira, conclusiva, fundamenta-se o triedro do cuidar e apontam-se indicações emancipatórias para o processo de trabalho dos profissionais.<br>Politicity of care is about handling the disruptive of the relation between help and power for the construction of the autonomy of subjects. Such conception is expressed mostly by the trihedron knowing to take a better care, taking care to confront and taking care to emancipate, that, in social-historical specific contexts and adapted to the working process in health, can constitute a reoriented reference of the domain relations. It is a theoretician-philosophical reflection, based in a doctorate thesis, which deepens the ambiguity of the care, conceived such by the way of being solidary, such as by becoming to be political. This article aims to indicate the applicability of the politicity conception of the care in the scope of the health professionals working process, signaling emancipatories potentialities. The first part makes a deep reflection about the policity of caring in its ontological, social and political dimensions, arguing about the tense relation existing between help and power which is present in the gesture of taking care. The second part contextualizes this theory in the unlike form of organizing and producing health care, presenting the discuss about the change of the attention model to the health. The third part is based in the emancipatory trihedron of caring and points emancipatory indications to the working process of the professionals