Cooperation and virulence in acute Pseudomonas aeruginosa infections

BACKGROUND: Efficient host exploitation by parasites is frequently likely to depend on cooperative behaviour. Under these conditions, mixed-strain infections are predicted to show lower virulence (host mortality) than are single-clone infections, due to competition favouring non-contributing social 'cheats' whose presence will reduce within-host growth. We tested this hypothesis using the cooperative production of iron-scavenging siderophores by the pathogenic bacterium Pseudomonas aeruginosa in an insect host. RESULTS: We found that infection by siderophore-producing bacteria (cooperators) results in more rapid host death than does infection by non-producers (cheats), and that mixtures of both result in intermediate levels of virulence. Within-host bacterial growth rates exhibited the same pattern. Crucially, cheats were more successful in mixed infections compared with single-clone infections, while the opposite was true of cooperators. CONCLUSION: These data demonstrate that mixed clone infections can favour the evolution of social cheats, and thus decrease virulence when parasite growth is dependent on cooperative behaviours

Age at Menarche, the Leg Length to Sitting Height Ratio, and Risk of Diabetes in Middle-Aged and Elderly Chinese Men and Women

To evaluate the associations of age at menarche and the leg length-to-sitting-height ratio, markers of adolescent growth, with risk of diabetes in later life.Information from 69,385 women and 55,311 men, aged 40-74 years from the Shanghai Women's Health Study and Shanghai Men's Health Study, were included in the current analyses. Diabetes status was ascertained through biennial in person follow-up. Cox models, with age as the time scale, were used.There were 2369 cases of diabetes (1831 women; 538 men) during an average of 7.3 and 3.6 years of follow-up of the women and men, respectively. In females, menarche age was inversely associated with diabetes risk after adjustment for birth cohort, education, and income (HR = 0.95, 0.92-0.98). In both genders, leg length-to-sitting-height ratio was inversely related to diabetes (HR = 0.88, 0.80-0.97 for men; HR = 0.91, 0.86-0.96 for women) after adjustment for birth cohort, education, and income. Further adjustment for adult BMI at study enrollment completely eliminated the associations of age at menarche (HR = 0.99, 0.96-1.02) and the leg length-to-sitting-height ratio (HR = 1.00, 0.91-1.10 for men; HR = 1.01, 0.96-1.07 for women) with diabetes risk.Our study suggests that markers of an early age at peak height velocity, i.e. early menarche age and low leg-length-to-sitting height ratio, may be associated with diabetes risk later in life and this association is likely to be mediated through obesity

Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla

<p>Abstract</p> <p>Background</p> <p>Omptins are a family of outer membrane proteases that have spread by horizontal gene transfer in Gram-negative bacteria that infect vertebrates or plants. Despite structural similarity, the molecular functions of omptins differ in a manner that reflects the life style of their host bacteria. To simulate the molecular adaptation of omptins, we applied site-specific mutagenesis to make Epo of the plant pathogenic <it>Erwinia pyrifoliae </it>exhibit virulence-associated functions of its close homolog, the plasminogen activator Pla of <it>Yersinia pestis</it>. We addressed three virulence-associated functions exhibited by Pla, i.e., proteolytic activation of plasminogen, proteolytic degradation of serine protease inhibitors, and invasion into human cells.</p> <p>Results</p> <p>Pla and Epo expressed in <it>Escherichia coli </it>are both functional endopeptidases and cleave human serine protease inhibitors, but Epo failed to activate plasminogen and to mediate invasion into a human endothelial-like cell line. Swapping of ten amino acid residues at two surface loops of Pla and Epo introduced plasminogen activation capacity in Epo and inactivated the function in Pla. We also compared the structure of Pla and the modeled structure of Epo to analyze the structural variations that could rationalize the different proteolytic activities. Epo-expressing bacteria managed to invade human cells only after all extramembranous residues that differ between Pla and Epo and the first transmembrane β-strand had been changed.</p> <p>Conclusions</p> <p>We describe molecular adaptation of a protease from an environmental setting towards a virulence factor detrimental for humans. Our results stress the evolvability of bacterial β-barrel surface structures and the environment as a source of progenitor virulence molecules of human pathogens.</p

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Sedentary behavior in adolescents: the 11-year follow-up of the 1993 Pelotas (Brazil) birth cohort study

The aim of this study was to estimate the prevalence of sedentary behavior and investigate associated factors in adolescents 11 years of age from the 1993 birth cohort in Pelotas, Rio Grande do Sul State, Brazil. Sedentary behavior was investigated with a questionnaire, and was defined as spending more than two hours per day watching television, playing videogames, or using the computer. Of the 4,452 adolescents interviewed, 98% reported watching television, 44% playing videogames, and 22% using the computer. The average time spent on each of these electronic media was 197, 36, and 17 minutes per day, respectively. Prevalence of sedentary behavior was 79.7% (95%CI: 78.6; 80.9) and showed a positive association with socioeconomic level and nutritional status and a negative association with well-being. These 11-year-olds spent extensive time at TV viewing, videogames, and the computer. Special attention should be given to the most exposed groups of adolescents, including the more affluent, overweight, and those with limited schooling.O objetivo deste estudo foi determinar a prevalência e investigar os fatores associados ao comportamento sedentário em adolescentes de 11 anos, pertencentes à coorte de nascimentos de 1993 de Pelotas, Rio Grande do Sul, Brasil. O comportamento sedentário foi coletado por meio de questionário, e definido como ficar mais de duas horas por dia assistindo à televisão, jogando videogame ou usando computador. Dos 4.452 adolescentes entrevistados, 98% assistiam à televisão, 44% jogavam videogame e 22% usavam computador. O tempo médio na frente de cada um desses meios eletrônicos foi, respectivamente, 197, 36 e 17 minutos por dia. A prevalência de comportamento sedentário foi de 79,7% (IC95%: 78,6; 80,9), e teve uma associação positiva com nível socioeconômico e com estado nutricional, e negativa com a escala de bem-estar. O tempo despendido em atividades como ver televisão, jogar videogame e usar computador foi elevado (média superior a 4 horas/dia). Maior atenção deve ser dada aos grupos mais expostos, tais como adolescentes de classe alta, acima do peso e com menor nível de bem-estar