136 research outputs found

    Uncovering the components of the Francisella tularensis virulence stealth strategy

    Get PDF
    Over the last decade, studies on the virulence of the highly pathogenic intracellular bacterial pathogen Francisella tularensis have increased dramatically. The organism produces an inert LPS, a capsule, escapes the phagosome to grow in the cytosol (FPI genes mediate phagosomal escape) of a variety of host cell types that include epithelial, endothelial, dendritic, macrophage, and neutrophil. This review focuses on the work that has identified and characterized individual virulence factors of this organism and we hope to highlight how these factors collectively function to produce the pathogenic strategy of this pathogen. In addition, several recent studies have been published characterizing F. tularensis mutants that induce host immune responses not observed in wild type F. tularensis strains that can induce protection against challenge with virulent F. tularensis. As more detailed studies with attenuated strains are performed, it will be possible to see how host models develop acquired immunity to Francisella. Collectively, detailed insights into the mechanisms of virulence of this pathogen are emerging that will allow the design of anti-infective strategies

    Soil and bark biodiversity forms discrete islands between vineyards that are not affected by distance or management regime

    Get PDF
    Within geographic regions the existing data suggests that physical habitat (bark, soil ,etc) is the strongest factor determining agroecosystem microbial community assemblage, followed by geographic location (site), and then management regime (organic, conventional, etc). The data also suggest community similarities decay with increasing geographic distance. However, integrated hypotheses for these observations have not been developed. We formalised and tested such hypotheses by sequencing 3.8 million bacterial 16S, fungal ITS2, and non-fungal eukaryotic COI barcodes deriving from 108 samples across two habitats (soil and bark) from six vineyards sites under conventional or conservation management. We found both habitat and site significantly affected community assemblage, with habitat the stronger for bacteria only, but there was no effect of management. There was no evidence for community similarity distance-decay within sites within each habitat. While communities significantly differed between vineyard sites, there was no evidence for between site community similarity distance-decay apart from bark bacterial communities, and no correlations with soil and bark pH apart from soil bacterial communities. Thus, within habitats vineyard sites represent discrete biodiversity islands, and while bacterial, fungal and non-fungal eukaryotic biodiversity mostly differs between sites, the distance by which they are separated does not define how different they are

    Francisella tularensis Schu S4 lipopolysaccharide core sugar and o-antigen mutants are attenuated in a mouse model of tularemia

    Get PDF
    The virulence factors mediating Francisella pathogenesis are being investigated, with an emphasis on understanding how the organism evades innate immunity mechanisms. Francisella tularensis produces a lipopolysaccharide (LPS) that is essentially inert and a polysaccharide capsule that helps the organism to evade detection by components of innate immunity. Using an F. tularensis Schu S4 mutant library, we identified strains that are disrupted for capsule and O-antigen production. These serum-sensitive strains lack both capsule production and O-antigen laddering. Analysis of the predicted protein sequences for the disrupted genes (FTT1236 and FTT1238c) revealed similarity to those for waa (rfa) biosynthetic genes in other bacteria. Mass spectrometry further revealed that these proteins are involved in LPS core sugar biosynthesis and the ligation of O antigen to the LPS core sugars. The 50% lethal dose (LD(50)) values of these strains are increased 100- to 1,000-fold for mice. Histopathology revealed that the immune response to the F. tularensis mutant strains was significantly different from that observed with wild-type-infected mice. The lung tissue from mutant-infected mice had widespread necrotic debris, but the spleens lacked necrosis and displayed neutrophilia. In contrast, the lungs of wild-type-infected mice had nominal necrosis, but the spleens had widespread necrosis. These data indicate that murine death caused by wild-type strains occurs by a mechanism different from that by which the mutant strains kill mice. Mice immunized with these mutant strains displayed >10-fold protective effects against virulent type A F. tularensis challenge

    Marine bacterial, archaeal and protistan association networks reveal ecological linkages

    Get PDF
    Microbes have central roles in ocean food webs and global biogeochemical processes, yet specific ecological relationships among these taxa are largely unknown. This is in part due to the dilute, microscopic nature of the planktonic microbial community, which prevents direct observation of their interactions. Here, we use a holistic (that is, microbial system-wide) approach to investigate time-dependent variations among taxa from all three domains of life in a marine microbial community. We investigated the community composition of bacteria, archaea and protists through cultivation-independent methods, along with total bacterial and viral abundance, and physico-chemical observations. Samples and observations were collected monthly over 3 years at a well-described ocean time-series site of southern California. To find associations among these organisms, we calculated time-dependent rank correlations (that is, local similarity correlations) among relative abundances of bacteria, archaea, protists, total abundance of bacteria and viruses and physico-chemical parameters. We used a network generated from these statistical correlations to visualize and identify time-dependent associations among ecologically important taxa, for example, the SAR11 cluster, stramenopiles, alveolates, cyanobacteria and ammonia-oxidizing archaea. Negative correlations, perhaps suggesting competition or predation, were also common. The analysis revealed a progression of microbial communities through time, and also a group of unknown eukaryotes that were highly correlated with dinoflagellates, indicating possible symbioses or parasitism. Possible ‘keystone’ species were evident. The network has statistical features similar to previously described ecological networks, and in network parlance has non-random, small world properties (that is, highly interconnected nodes). This approach provides new insights into the natural history of microbes

    Iron Deficiency and the Well-being of Older Adults: Early Results From a Randomized Nutrition Intervention

    Full text link
    Iron deficiency is widespread throughout the developing world. We provide new evidence on the effect of iron deficiency on economic and social prosperity of older adults drawing on data from a random assignment treatment-control design intervention. The Work and Iron Status Evaluation is an on-going study following over 17,000 individuals in Central Java, Indonesia. Half the respondents receive a treatment of 120 mg of iron every week for a year; the controls receive a placebo. Compliance is monitored carefully. Results from the first six months of the intervention are presented for adults age 30 through 70 years. Males who were iron deficient prior to the intervention and who are assigned to the treatment are better off in terms of physical health, psycho-social health and economic success. These men are more likely to be working, sleep less, lose less work time to illness, are more energetic, more able to conduct physically arduous activities and their psycho-social health is better. There is evidence that economic productivity of these males also increased. Among iron-deficient males assigned to the treatment who were also self-employed prior to the baseline, hourly earnings rose substantially and so they earned more on a monthly basis. Benefits for women are in the same direction but the effects are more muted. The results provide unambiguous evidence in support of the hypothesis that health has a causal effect on economic prosperity of males during middle and older ages

    Influence of practice schedules and attention on skill development and retention

    Get PDF
    Focus of attention during dual-tasks and practice schedules are important components of motor skill performance and learning; often studied in isolation. The current study required participants to complete a simple key-pressing task under a blocked or random practice schedule. To manipulate attention, participants reported their finger position (i.e., skill-focused attention) or the pitch of an auditory tone (i.e., extraneous attention) while performing two variations of a dual-task key-pressing task. Analyses were conducted at baseline, 10 min and 24 h after acquisition. The results revealed that participants in a blocked schedule, extraneous focus condition had significantly faster movement times during retention compared to a blocked schedule, skill focus condition. Furthermore, greatest improvements from baseline to immediate and delayed retention were evident for an extraneous attention compared to the skill-focused attention, regardless of practice schedule. A discussion of the unique benefits an extraneous focus of attention may have on the learning process during dual-task conditions is presented

    Hypoaminoacidemia underpins glucagon-mediated energy expenditure and weight loss

    Full text link
    Glucagon analogs show promise as components of next-generation, multi-target, anti-obesity therapeutics. The biology of chronic glucagon treatment, in particular, its ability to induce energy expenditure and weight loss, remains poorly understood. Using a long-acting glucagon analog, G108, we demonstrate that glucagon-mediated body weight loss is intrinsically linked to the hypoaminoacidemia associated with its known amino acid catabolic action. Mechanistic studies reveal an energy-consuming response to low plasma amino acids in G108-treated mice, prevented by dietary amino acid supplementation and mimicked by a rationally designed low amino acid diet. Therefore, low plasma amino acids are a pre-requisite for G108-mediated energy expenditure and weight loss. However, preventing hypoaminoacidemia with additional dietary protein does not affect the ability of G108 to improve glycemia or hepatic steatosis in obese mice. These studies provide a mechanism for glucagon-mediated weight loss and confirm the hepatic glucagon receptor as an attractive molecular target for metabolic disease therapeutics
    • …
    corecore