A Host-Pathogen Interaction Screen Identifies ada2 as a Mediator of Candida glabrata Defenses Against Reactive Oxygen Species.

Candida glabrata (C. glabrata) forms part of the normal human gut microbiota but can cause life-threatening invasive infections in immune-compromised individuals. C. glabrata displays high resistance to common azole antifungals, which necessitates new treatments. In this investigation, we identified five C. glabrata deletion mutants (∆ada2, ∆bas1, ∆hir3, ∆ino2 and ∆met31) from a library of 196 transcription factor mutants that were unable to grow and activate an immune response in Drosophila larvae. This highlighted the importance of these transcription factors in C. glabrata infectivity. Further ex vivo investigation into these mutants revealed the requirement of C. glabrata ADA2 for oxidative stress tolerance. We confirmed this observation in vivo whereby growth of the C. glabrata Δada2 strain was permitted only in flies with suppressed production of reactive oxygen species (ROS). Conversely, overexpression of ADA2 promoted C. glabrata replication in infected wild type larvae resulting in larval killing. We propose that ADA2 orchestrates the response of C. glabrata against ROS-mediated immune defenses during infection. With the need to find alternative antifungal treatment for C. glabrata infections, genes required for survival in the host environment, such as ADA2, provide promising potential targets.

Interaction Between Familial Transmission and a Constitutively Active Immune System Shapes Gut Microbiota in Drosophila melanogaster.

Resident gut bacteria are constantly influencing the immune system, yet the role of the immune system in shaping microbiota composition during an organism's life span has remained unclear. Experiments in mice have been inconclusive due to differences in husbandry schemes that led to conflicting results. We used Drosophila as a genetically tractable system with a simpler gut bacterial population structure streamlined genetic backgrounds and established cross schemes to address this issue. We found that, depending on their genetic background, young flies had microbiota of different diversities that converged with age to the same Acetobacteraceae-dominated pattern in healthy flies. This pattern was accelerated in immune-compromised flies with higher bacterial load and gut cell death. Nevertheless, immune-compromised flies resembled their genetic background, indicating that familial transmission was the main force regulating gut microbiota. In contrast, flies with a constitutively active immune system had microbiota readily distinguishable from their genetic background with the introduction and establishment of previously undetectable bacterial families. This indicated the influence of immunity over familial transmission. Moreover, hyperactive immunity and increased enterocyte death resulted in the highest bacterial load observed starting from early adulthood. Cohousing experiments showed that the microenvironment also played an important role in the structure of the microbiota where flies with constitutive immunity defined the gut microbiota of their cohabitants. Our data show that, in Drosophila, constitutively active immunity shapes the structure and density of gut microbiota.

Exploring interactions between pathogens and the Drosophila gut.

Gastrointestinal infection can provoke substantial disturbance at both a local as well as at a systemic level and may evolve into a chronic disease state. Our growing knowledge of gut-pathogen interactions has been based to a large extent on the use of genetically tractable model hosts such as the fruit fly Drosophila melanogaster. In this review we will summarise the growing literature and critically address the advantages and disadvantages of using this model to extrapolate results from studying pathogen virulence and intestinal responses to humans.

Interactions between temperature and sugars in the regulation of leaf senescence in the perennial herb Arabis alpina L.

Annual plants usually flower and set seed once before senescence results in the death of the whole plant (monocarpic senescence). Leaf senescence also occurs in polycarpic perennials; even in "evergreen" species individual leaves senesce. In the annual model Arabidopsis thaliana sugars accumulate in the senescent leaves and senescence is accelerated by high sugar availability. Similar to A. thaliana, sugar contents increased with leaf age in the perennial Arabis alpina grown under warm conditions (22 °C day/18 night). At 5 °C, sugar contents in non-senescent leaves were higher than at a warm temperature, but dependent on the accession, either sugars did not accumulate or their contents decreased in old leaves. In A. alpina plants grown in their natural habitat in the Alps, sugar contents declined with leaf age. Growth at a cold temperature slightly delayed senescence in A. alpina. In both warm and cold conditions, an external glucose supply accelerated senescence, but natural variation was found in this response. In conclusion, sugar accumulation under warm conditions could accelerate leaf senescence in A. alpina plants, but genotype-specific responses and interactions with growth temperature are likely to influence senescence under natural conditions.

Recommendations to improve physical activity among teenagers--a qualitative study with ethnic minority and European teenagers.

BACKGROUND: To understand the key challenges and explore recommendations from teenagers to promote physical activity with a focus on ethnic minority children. METHODS: Focus groups with teenagers aged 16-18 of Bangladeshi, Somali or Welsh descent attending a participating school in South Wales, UK. There were seventy four participants (18 Somali, 24 Bangladeshi and 32 Welsh children) divided into 12 focus groups. RESULTS: The boys were more positive about the benefits of exercise than the girls and felt there were not enough facilities or enough opportunity for unsupervised activity. The girls felt there was a lack of support to exercise from their family. All the children felt that attitudes to activity for teenagers needed to change, so that there was more family and community support for girls to be active and for boys to have freedom to do activities they wanted without formal supervision. It was felt that older children from all ethnic backgrounds should be involved more in delivering activities and schools needs to provide more frequent and a wider range of activities. CONCLUSIONS: This study takes a child-focused approach to explore how interventions should be designed to promote physical activity in youth. Interventions need to improve access to facilities but also counteract attitudes that teenagers should be studying or working and not 'hanging about' playing with friends. Thus, the value of activity for teenagers needs to be promoted not just among the teenagers but with their teachers, parents and members of the community.

Risk factors for childhood obesity at age 5: analysis of the millennium cohort study.

BACKGROUND: Weight at age 5 is a predictor for future health of the individual. This study examines risk factors for childhood obesity with a focus on ethnicity. METHODS: Data from the Millennium Cohort study were used. 17,561 singleton children of White/European (n = 15,062), Asian (n = 1,845) or African (n = 654) background were selected. Logistic regression and likelihood ratio tests were used to examine factors associated with obesity at age 5. All participants were interviewed in their own homes. The main exposures examined included; Birth weight, sedentary lifestyle, family health behaviours, ethnicity, education and income. RESULTS: Children with a sedentary lifestyle, large at birth, with high risk family health behaviours (overweight mothers, smoking near the child, missing breakfast) and from a family with low income or low educational attainment, were more likely to be obese regardless of ethnicity. Feeding solid food before 3 months was associated with obesity in higher income White/European families. Even when controlling for socioeconomic status, ethnic background is an important independent risk factor for childhood obesity [Odds ratio of obesity; was 1.7 (95%CI: 1.2-2.3) for Asian and 2.7 (95%CI: 1.9-3.9) for African children, compared to White/European]. The final adjusted model suggests that increasing income does not have a great impact on lowering obesity levels, but that higher academic qualifications are associated with lower obesity levels [Odds of obesity: 0.63 (95%CI: 0.52-0.77) if primary carer leaves school after age 16 compared at age 16]. CONCLUSIONS: Education of the primary carer is an important modifiable factor which can be targeted to address rising obesity levels in children. Interventions should be family centred supporting and showing people how they can implement lifestyle changes in their family.