Type IV Secretion-Dependent Activation of Host MAP Kinases Induces an Increased Proinflammatory Cytokine Response to Legionella pneumophila

The immune system must discriminate between pathogenic and nonpathogenic microbes in order to initiate an appropriate response. Toll-like receptors (TLRs) detect microbial components common to both pathogenic and nonpathogenic bacteria, whereas Nod-like receptors (NLRs) sense microbial components introduced into the host cytosol by the specialized secretion systems or pore-forming toxins of bacterial pathogens. The host signaling pathways that respond to bacterial secretion systems remain poorly understood. Infection with the pathogen Legionella pneumophila, which utilizes a type IV secretion system (T4SS), induced an increased proinflammatory cytokine response compared to avirulent bacteria in which the T4SS was inactivated. This enhanced response involved NF-κB activation by TLR signaling as well as Nod1 and Nod2 detection of type IV secretion. Furthermore, a TLR- and RIP2-independent pathway leading to p38 and SAPK/JNK MAPK activation was found to play an equally important role in the host response to virulent L. pneumophila. Activation of this MAPK pathway was T4SS-dependent and coordinated with TLR signaling to mount a robust proinflammatory cytokine response to virulent L. pneumophila. These findings define a previously uncharacterized host response to bacterial type IV secretion that activates MAPK signaling and demonstrate that coincident detection of multiple bacterial components enables immune discrimination between virulent and avirulent bacteria

Finding the Needles in the Metagenome Haystack

In the collective genomes (the metagenome) of the microorganisms inhabiting the Earth’s diverse environments is written the history of life on this planet. New molecular tools developed and used for the past 15 years by microbial ecologists are facilitating the extraction, cloning, screening, and sequencing of these genomes. This approach allows microbial ecologists to access and study the full range of microbial diversity, regardless of our ability to culture organisms, and provides an unprecedented access to the breadth of natural products that these genomes encode. However, there is no way that the mere collection of sequences, no matter how expansive, can provide full coverage of the complex world of microbial metagenomes within the foreseeable future. Furthermore, although it is possible to fish out highly informative and useful genes from the sea of gene diversity in the environment, this can be a highly tedious and inefficient procedure. Microbial ecologists must be clever in their pursuit of ecologically relevant, valuable, and niche-defining genomic information within the vast haystack of microbial diversity. In this report, we seek to describe advances and prospects that will help microbial ecologists glean more knowledge from investigations into metagenomes. These include technological advances in sequencing and cloning methodologies, as well as improvements in annotation and comparative sequence analysis. More significant, however, will be ways to focus in on various subsets of the metagenome that may be of particular relevance, either by limiting the target community under study or improving the focus or speed of screening procedures. Lastly, given the cost and infrastructure necessary for large metagenome projects, and the almost inexhaustible amount of data they can produce, trends toward broader use of metagenome data across the research community coupled with the needed investment in bioinformatics infrastructure devoted to metagenomics will no doubt further increase the value of metagenomic studies in various environments

Chronic Renal Disease In Children Aged 5-18 Years: A Population-Based Survey In Turkey, The Credit-C Study

Background. Data on the epidemiology of chronic kidney disease (CKD), which is a serious health problem and refers to a condition related to irreversible kidney damage that further progress to end-stage renal disease in children, are insufficient and data that are available were based on hospital records. The aim of this nationwide, population-based field study was to determine the prevalence of CKD in children in Turkey and to evaluate the association between CKD and possible risk factors such as obesity and hypertension. Methods. The study was the paediatric stratum (3622 children aged 5-18 years) of the previously published population-based survey of Chronic REnal Disease In Turkey (CREDIT study). Medical data were collected through home visits and interviews between November 2007 and July 2008; height, weight and blood pressure were also measured. Serum creatinine, total cholesterol, uric acid and complete blood count were determined from 12-h fasting blood samples, and spot urine tests were performed for subjects who gave consent to laboratory evaluation. Results. Following adjustment according to gender, residence, age groups and geographical regions, the prevalence of children with estimated glomerular filtration rate (eGFR) <75 mL/min/1.73 m(2) was 0.94 [95% confidence interval (CI): 0.63-1.35], and the prevalence of children with CKD Stages 3-5 [National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (K/DOQI)] was 2600 (95% CI 1100-5100) per million age related population. The mean eGFR was found to increase with age; the ratios of children with eGFR <90 and <75 mL/min/1.73 m(2) were higher in younger age groups. The frequencies of overweight and obese children were 9.3 and 8.9%, respectively, and the mean eGFR was lower in patients with higher body mass index. The prevalence of hypertension and hypercholesterolaemia was 6.1 and 5.8%, respectively; the mean eGFR was lower in children with hypercholesterolaemia. Conclusions. This is the first population-based CKD study performed in children aged 5-18 years. The prevalence of CKD in our study was 25-100 times greater than that found in previous hospital-based studies. Our data suggest that approaches focusing on patients in tertiary centres are likely to lead to patients being missed at early stages of CKD and that a vast majority of these children will never develop symptomatic CKD during childhood.WoSScopu