Complete Killing of Caenorhabditis elegans by Burkholderia pseudomallei Is Dependent on Prolonged Direct Association with the Viable Pathogen

Background: Burkholderia pseudomallei is the causative agent of melioidosis, a disease of significant morbidity and mortality in both human and animals in endemic areas. Much remains to be known about the contributions of genotypic variations within the bacteria and the host, and environmental factors that lead to the manifestation of the clinical symptoms of melioidosis. Methodology/Principal Findings: In this study, we showed that different isolates of B. pseudomallei have divergent ability to kill the soil nematode Caenorhabditis elegans. The rate of nematode killing was also dependent on growth media: B. pseudomallei grown on peptone-glucose media killed C. elegans more rapidly than bacteria grown on the nematode growth media. Filter and bacteria cell-free culture filtrate assays demonstrated that the extent of killing observed is significantly less than that observed in the direct killing assay. Additionally, we showed that B. pseudomallei does not persistently accumulate within the C. elegans gut as brief exposure to B. pseudomallei is not sufficient for C. elegans infection. Conclusions/Significance: A combination of genetic and environmental factors affects virulence. In addition, we have also demonstrated that a Burkholderia-specific mechanism mediating the pathogenic effect in C. elegans requires proliferating B

Nutritional profile and obesity: results from a random‑sample population‑based study in Córdoba, Argentina

Introduction Obesity is a chronic, heterogeneous, multifactorial disease, which has sharply increased in prevalence in both developed and developing countries. This study aimed to estimate the prevalence of obesity and to identify socio-demographic risk factors associated with it, with special emphasis on diet. Methods Nutritional status, demographic characteristics, lifestyle habits, and food consumption patterns derived from a Food Frequency Questionnaire were investigated. Exhaustive exploratory analyses were performed in order to describe dietary patterns, and logistic regression models were used for odds ratio estimation. Results The study included 4328 subjects, over 18 years old and resident in Cordoba city. The prevalence of overweight and obesity was 34 and 17 %, respectively, with 60 % in men and 45 % in women of BMI ≥ 25. Obesity risk factors were high intake of sodium, refined grains, starchy vegetables, and snacks. A lower risk of overweight and obesity was associated with an adequate, moderate intake of meats, eggs, alcoholic beverages, sugar and sweets, milk, yogurt, and pulses. Conclusions A high intake of snacks, refined grains, starchy vegetables and sodium and low intake of yogurt, milk, pulses, and whole grains seem to be associated with the emergence and high prevalence of obesity in Cordoba, Argentina.publishedVersionFil: Aballay, Laura Rosana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Escuela de Nutrición. Estadística y Bioestadística; ArgentinaFil: Aballay, Laura Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: De la Quintana, Ana Gabriela. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Escuela de Nutrición; Argentina.Fil: Díaz, María del Pilar. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Escuela de Nutrición. Estadística y Bioestadística; Argentina.Fil: Díaz, María del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: Osella, Alberto R. Hospital Saverio de Bellis. Laboratorio de Epidemiologia y Bioestadística; Italia

Nitric Oxide Antagonizes the Acid Tolerance Response that Protects Salmonella against Innate Gastric Defenses

Reactive nitrogen species (RNS) derived from dietary and salivary inorganic nitrogen oxides foment innate host defenses associated with the acidity of the stomach. The mechanisms by which these reactive species exert antimicrobial activity in the gastric lumen are, however, poorly understood.The genetically tractable acid tolerance response (ATR) that enables enteropathogens to survive harsh acidity was screened for signaling pathways responsive to RNS. The nitric oxide (NO) donor spermine NONOate derepressed the Fur regulon that controls secondary lines of resistance against organic acids. Despite inducing a Fur-mediated adaptive response, acidified RNS largely repressed oral virulence as demonstrated by the fact that Salmonella bacteria exposed to NO donors during mildly acidic conditions were shed in low amounts in feces and exhibited ameliorated oral virulence. NO prevented Salmonella from mounting a de novo ATR, but was unable to suppress an already functional protective response, suggesting that RNS target regulatory cascades but not their effectors. Transcriptional and translational analyses revealed that the PhoPQ signaling cascade is a critical ATR target of NO in rapidly growing Salmonella. Inhibition of PhoPQ signaling appears to contribute to most of the NO-mediated abrogation of the ATR in log phase bacteria, because the augmented acid sensitivity of phoQ-deficient Salmonella was not further enhanced after RNS treatment.Since PhoPQ-regulated acid resistance is widespread in enteric pathogens, the RNS-mediated inhibition of the Salmonella ATR described herein may represent a common component of innate host defenses

RNAi Screen of DAF-16/FOXO Target Genes in C. elegans Links Pathogenesis and Dauer Formation

The DAF-16/FOXO transcription factor is the major downstream output of the insulin/IGF1R signaling pathway controlling C. elegans dauer larva development and aging. To identify novel downstream genes affecting dauer formation, we used RNAi to screen candidate genes previously identified to be regulated by DAF-16. We used a sensitized genetic background [eri-1(mg366); sdf-9(m708)], which enhances both RNAi efficiency and constitutive dauer formation (Daf-c). Among 513 RNAi clones screened, 21 displayed a synthetic Daf-c (SynDaf) phenotype with sdf-9. One of these genes, srh-100, was previously identified to be SynDaf, but twenty have not previously been associated with dauer formation. Two of the latter genes, lys-1 and cpr-1, are known to participate in innate immunity and six more are predicted to do so, suggesting that the immune response may contribute to the dauer decision. Indeed, we show that two of these genes, lys-1 and clc-1, are required for normal resistance to Staphylococcus aureus. clc-1 is predicted to function in epithelial cohesion. Dauer formation exhibited by daf-8(m85), sdf-9(m708), and the wild-type N2 (at 27°C) were all enhanced by exposure to pathogenic bacteria, while not enhanced in a daf-22(m130) background. We conclude that knockdown of the genes required for proper pathogen resistance increases pathogenic infection, leading to increased dauer formation in our screen. We propose that dauer larva formation is a behavioral response to pathogens mediated by increased dauer pheromone production

Ventilatory function and cardiovascular disease risk factors: A cross-sectional study in young adults

© Garcia-Larsen et al.Background: The association between impaired lung function and cardiovascular disease (CVD) risk factors has been shown in adults. However, there is little evidence of such an association in young adults, particularly from South America, where the burden of CVD and chronic obstructive pulmonary disease (COPD) is as high as that observed in more developed countries. We therefore investigated the relation between CVD risk factors including metabolic syndrome (MS), and lung function status in young adults from Chile. Methods: 970 subjects from a sample of 998 adults born between 1974 and 1978 in Limache, Chile, were studied. A Spanish translation of the European Community Respiratory Health Survey (ECRHS) questionnaire was used. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured. Weight, height, waist circumference (WC), blood pressure, Homeostatic model assessment (HOMA-IR), triglycerides, high density lipoprotein (HDL), glyca