New concepts in C. difficile management

BackgroundClostridium difficile infection is transmitted via spores, and the disease is mediated via secreted toxins. It represents a significant healthcare problem, and clinical presentation can range from asymptomatic carriage to life-threatening pseudomembranous colitis.Sources of datapublications in the field, with a focus on recent developments and concepts.Areas of agreementinfection control measures, antibiotic stewardship and current management of the initial episode of C. difficile infection.Areas of controversyselection and sequence of interventions for the management of recurrent C. difficile infection; management of persistent carriers of toxigenic C. difficile in patients at high risk of subsequent C. difficile infection.Growing pointsuse of faecal microbiota transplantation for recurrent C. difficile infection.Areas timely for developing researchrole of specific microbiota-mediated interventions and vaccination in the treatment and prevention of C. difficile infection

Effect of nutrient composition on the in vitro growth of urogenital lactobacilli and uropathogens

Lactobacillus rhamnosus is a human commensal with known immunomodulatory properties. To date the mechanism of these immunomodulatory effects is not well understood. To unravel the immunomodulatory signalling mechanism, we investigated the effects of two strains of L.rhamnosus, L.rhamnosus GG and GR-1, in modulating production of tumour necrosis factor-α (TNF) in human monocytic cell line THP-1 and mouse macrophages. Live L.rhamnosus GG and GR-1 or their spent culture supernatant induced minuscule amounts of TNF production but large quantities of granulocyte-colony stimulating factor (G-CSF) in macrophages compared with those induced by pathogenic Escherichia coli GR-12 and Enterococcus faecalis. By using neutralizing antibodies and G-CSF receptor knockout mice, we demonstrated that G-CSF secreted from L. rhamnosus GG- and GR-1-exposed macrophages suppressed TNF production induced by E. coli- or lipopolysaccharide-activated macrophages through a paracrine route. The suppression of TNF production by G-CSF was mediated through activation of STAT3 and subsequent inhibition of c-Jun-N-terminal kinases (JNKs). The inhibition of JNK activation required STAT3α-mediated de novo protein synthesis. This demonstrates a novel role of G-CSF in L. rhamnosus-triggered anti-inflammatory effects and its mechanism in the suppression of TNF production in macrophages. © 2006 The Authors; Journal compilation 2006 Blackwell Publishing Ltd

eALPS: Estimating Abundance Levels in Pooled Sequencing Using Available Genotyping Data

The recent advances in high-throughput sequencing technologies bring the potential of a better characterization of the genetic variation in humans and other organisms. In many occasions, either by design or by necessity, the sequencing procedure is performed on a pool of DNA samples with different abundances, where the abundance of each sample is unknown. Such a scenario is naturally occurring in the case of metagenomics analysis where a pool of bacteria is sequenced, or in the case of population studies involving DNA pools by design. Particularly, various pooling designs were recently suggested that can identify carriers of rare alleles in large cohorts, dramatically reducing the cost of such large-scale sequencing projects. A fundamental problem with such approaches for population studies is that the uncertainly of DNA proportions from different individuals in the pools might lead to spurious associations. Fortunately, it is often the case that the genotype data of at least some of the individuals in the pool is known. Here, we propose a method (eALPS) that uses the genotype data in conjunction with the pooled sequence data in order to accurately estimate the proportions of the samples in the pool, even in cases where not all individuals in the pool were genotyped (eALPS-LD). Using real data from a sequencing pooling study of Non-Hodgkin's Lymphoma, we demonstrate that the estimation of the proportions is crucial, since otherwise there is a risk for false discoveries. Additionally, we demonstrate that our approach is also applicable to the problem of quantification of species in metagenomics samples (eALPS-BCR), and is particularly suitable for metagenomic quantification of closely-related species. © 2013 Springer-Verlag