Capping proteins regulate fungal development,DON-toxisome formation and virulence in Fusarium graminearum

Deoxynivalenol (DON) is an important trichothecene mycotoxin produced by the cereal pathogen Fusarium graminearum. DON is synthesized in organized endoplasmic reticulum structures called toxisomes. However, the mechanism for toxisome formation and the components of toxisomes are not yet fully understood. In a previous study, we found that myosin I (FgMyo1)-actin cytoskeleton participated in toxisome formation. In the current study, we identified two new components of toxisomes, the actin capping proteins (CAPs) FgCapA and FgCapB. These two CAPs form a heterodimer in F. graminearum, and physically interact with FgMyo1 and Tri1. The deletion mutants ΔFgcapA and ΔFgcapB and the double deletion mutant ΔΔFgcapA/B dramatically reduced hyphal growth, asexual and sexual reproduction and endocytosis. More importantly, the deletion mutants markedly disrupted toxisome formation and DON production, and attenuated virulence in planta. Collectively, these results suggest that the actin CAPs are associated with toxisome formation and contribute to the virulence and development of F. graminearum.     

Biomarker Changes Associated with Tuberculin Skin Test (TST) Conversion: A Two-Year Longitudinal Follow-Up Study in Exposed Household Contacts

Background

A high prevalence (50–80%) of Tuberculin Skin Test Positivity (TST+ ≥10 mm indurations) has been reported in TB endemic countries. This pool forms a huge reservoir for new incident TB cases. However, immune biomarkers associated with TST conversion are largely unknown. The objective of this study was to identify immune biomarkers associated with TST conversion after acute Mycobacterium tuberculosis (MTB) exposure.

Methodology/Principal Findings

A 24 month longitudinal study was carried out in a recently MTB exposed cohort of household contacts (HC = 93; 75% TST+). Control group consisted of unexposed community controls (EC = 59; 46%TST+). Cytokine secretion was assessed in whole blood cultures in response to either mycobacterial culture filtrate (CF) antigens or mitogens (PHA or LPS) using Elisa methodology. Compared to the EC group, the HC group at recruitment (Kruskal-Wallis Test) showed significantly suppressed IFN γ (p = 0.0001), raised IL-10 (p = 0.0005) and raised TNF α (p = 0.001) in response to CF irrespective of their TST status. Seventeen TST-HC, showed TST conversion when retested at 6 months. Post TST conversion (paired t tests) significant increases were observed for CF induced IFN γ (p = 0.038), IL-10 (p = 0.001) and IL-6 (p = 0.006). Cytokine responses were also compared in the exposed HC group with either recent infection [(TST converters (N = 17)] or previous infection [TST+ HC (N = 54)] at 0, 6, 12 and 24 months using ANOVA on repeated measures. Significant differences between the exposed HC groups were noted only at 6 months. CF induced IFN γ was higher in previously infected HC group (p = 0.038) while IL-10 was higher in recently infected HC group (p = 0.041). Mitogen induced cytokine secretion showed similar differences for different group.

Conclusions/Significance

Our results suggest that TST conversion is associated with early increases in IFN γ and IL-10 responses and precedes latency by several months post exposure.     

Updating the Role of Probiotics,Prebiotics, and Synbiotics for Tilapia Aquaculture as Leading Candidates for Food Sustainability: a Review

Probiotics and Antimicrobial Proteins - Tilapia production has significantly increased over the past few years due to the adoption of semi-intensive and intensive aquaculture technologies. However,...     

Mortality amongst Patients with Influenza-Associated Severe Acute Respiratory Illness,South Africa, 2009-2013

Introduction

Data on the burden and risk groups for influenza-associated mortality from Africa are limited. We aimed to estimate the incidence and risk-factors for in-hospital influenza-associated severe acute respiratory illness (SARI) deaths.

Methods

Hospitalised patients with SARI were enrolled prospectively in four provinces of South Africa from 2009–2013. Using polymerase chain reaction, respiratory samples were tested for ten respiratory viruses and blood for pneumococcal DNA. The incidence of influenza-associated SARI deaths was estimated at one urban hospital with a defined catchment population.

Results

We enrolled 1376 patients with influenza-associated SARI and 3% (41 of 1358 with available outcome data) died. In patients with available HIV-status, the case-fatality proportion (CFP) was higher in HIV-infected (5%, 22/419) than HIV-uninfected individuals (2%, 13/620; p = 0.006). CFPs varied by age group, and generally increased with increasing age amongst individuals >5 years (p<0.001). On multivariable analysis, factors associated with death were age-group 45–64 years (odds ratio (OR) 4.0, 95% confidence interval (CI) 1.01–16.3) and ≥65 years (OR 6.5, 95%CI 1.2–34.3) compared to 1–4 year age-group who had the lowest CFP, HIV-infection (OR 2.9, 95%CI 1.1–7.8), underlying medical conditions other than HIV (OR 2.9, 95%CI 1.2–7.3) and pneumococcal co-infection (OR 4.1, 95%CI 1.5–11.2). The estimated incidence of influenza-associated SARI deaths per 100,000 population was highest in children <1 year (20.1, 95%CI 12.1–31.3) and adults aged 45–64 years (10.4, 95%CI 8.4–12.9). Adjusting for age, the rate of death was 20-fold (95%CI 15.0–27.8) higher in HIV-infected individuals than HIV-uninfected individuals.

Conclusion

Influenza causes substantial mortality in urban South Africa, particularly in infants aged <1 year and HIV-infected individuals. More widespread access to antiretroviral treatment and influenza vaccination may reduce this burden.     

Epidemiology of Severe Acute Respiratory Illness (SARI) among Adults and Children Aged ≥5 Years in a High HIV-Prevalence Setting, 2009–2012

ObjectiveThere are few published studies describing severe acute respiratory illness (SARI) epidemiology amongst older children and adults from high HIV-prevalence settings. We aimed to describe SARI epidemiology amongst individuals aged ≥5 years in South Africa.MethodsWe conducted prospective surveillance for individuals with SARI from 2009–2012. Using polymerase chain reaction, respiratory samples were tested for ten viruses, and blood for pneumococcal DNA. Cumulative annual SARI incidence was estimated at one site with population denominators.FindingsWe enrolled 7193 individuals, 9% (621/7067) tested positive for influenza and 9% (600/6519) for pneumococcus. HIV-prevalence was 74% (4663/6334). Among HIV-infected individuals with available data, 41% of 2629 were receiving antiretroviral therapy (ART). The annual SARI hospitalisation incidence ranged from 325-617/100,000 population. HIV-infected individuals experienced a 13–19 times greater SARI incidence than HIV-uninfected individuals (p<0.001). On multivariable analysis, compared to HIV-uninfected individuals, HIV-infected individuals were more likely to be receiving tuberculosis treatment (odds ratio (OR):1.7; 95%CI:1.1–2.7), have pneumococcal infection (OR 2.4; 95%CI:1.7–3.3) be hospitalised for >7 days rather than <2 days (OR1.7; 95%CI:1.2–2.2) and had a higher case-fatality ratio (8% vs 5%;OR1.7; 95%CI:1.2–2.3), but were less likely to be infected with influenza (OR 0.6; 95%CI:0.5–0.8). On multivariable analysis, independent risk indicators associated with death included HIV infection (OR 1.8;95%CI:1.3–2.4), increasing age-group, receiving mechanical ventilation (OR 6.5; 95%CI:1.3–32.0) and supplemental-oxygen therapy (OR 2.6; 95%CI:2.1–3.2).ConclusionThe burden of hospitalized SARI amongst individuals aged ≥5 years is high in South Africa. HIV-infected individuals are the most important risk group for SARI hospitalization and mortality in this setting.     

Glucocorticoid responses to stress in castrate and testosterone-replaced rams

Stress is an important contributor to cardiovascular disease and to reduced immunity and fertility. As the role of androgens in stress is uncertain, we investigated the effects of testosterone (T) on hormonal responses to stress in conscious Romney Marsh wethers. Six T-treated sheep and six control sheep were stressed by exposure to a psychological and a metabolic stimulus. Baseline glucose levels were significantly lower in the treated animals compared with controls (p=0.002). T treatment significantly attenuated ACTH (p<0.01) and cortisol (p<0.05) responses to metabolic stress. Following psychological stress, ACTH responses were significantly lower in treated sheep compared with controls (p<0.05), but differences in mean cortisol responses did not reach significance. There were no significant differences in epinephrine or norepinephrine responses following either stressor. We conclude that T replacement in wethers lowers glucose and attenuates responses to metabolic and psychological stress. While the implications of these results for human physiology require further studies, they suggest that male hypogonadism may play a role in determining the risk of cardiovascular disease and diabetes.     

Nutrient and secondary metabolite concentrations in a savanna are independently affected by large herbivores and shoot growth rate

Carbon-based secondary metabolites (CBSMs) such as tannins are assumed to function as plant defences against herbivores. CBSMs are thought to be inversely related to growth rate and nutrient concentrations because a physiological trade-off exists between cellular growth and differentiation, but CBSM concentrations can be altered by herbivory-induced changes in the trade-off. We predicted that a significant interaction exists between herbivory and growth phase, such that the effects of large herbivores (or their exclusion) on nutrient or CBSM concentrations are greatest during phases of rapid shoot or leaf growth. Leaf samples were collected during phases of different growth rate from six woody species 4 years after establishment of a large-scale long-term herbivore exclusion experiment in Kruger National Park, South Africa. Samples were analysed for N, P, condensed tannins and total phenolics. Interactions between growth phase and herbivores were rare. However, the assumption that elevated nutrients and reduced CBSMs occurs during fast phases of growth was supported by four species (consistent with the growth-differentiation balance hypothesis), but not the other two. Large herbivores generally did not affect nutrients, but CBSMs in four species were reduced by large herbivores other than elephants, while CBSMs in two species were reduced by elephants. Carbon limitation ultimately prevailed among woody plants taller than 2 m under long-term browsing. Large herbivores and plant growth phase are independent and important determinants of nutrients or CBSMs in African savannas, but the effects depend on the interacting assemblages of species, which poses challenges to the application of current general hypotheses of plant defence.