Bacteria and archaea have developed multiple antiviral mechanisms, and genomic evidence indicates that several of these antiviral systems co-occur in the same strain. Here, we introduce DefenseFinder, a tool that automatically detects known antiviral systems in prokaryotic genomes. We use DefenseFinder to analyse 21000 fully sequenced prokaryotic genomes, and find that antiviral strategies vary drastically between phyla, species and strains. Variations in composition of antiviral systems correlate with genome size, viral threat, and lifestyle traits. DefenseFinder will facilitate large-scale genomic analysis of antiviral defense systems and the study of host-virus interactions in prokaryotes.

Meckel syndrome (MKS) is a rare autosomal recessive lethal condition characterized by central nervous system malformations (typically occipital meningoencephalocele), postaxial polydactyly, multicystic kidney dysplasia, and ductal proliferation in the portal area of the liver. MKS is genetically heterogeneous and three loci have been mapped respectively on 17q23 (MKS1), 11q13 (MKS2), and 8q24 (MKS3). Very recently, two genes have been identified: MKS1/FLJ20345 on 17q in Finnish kindreds, carrying the same intronic deletion, c.1408-35_c.1408-7del29, and MKS3/TMEM67 on 8q in families from Pakistan and Oman. Here we report the genotyping of the MKS1 and MKS3 genes in a large, multiethnic cohort of 120 independent cases of MKS. Our first results indicate that the MKS1 and MKS3 genes are each responsible for about 7% of MKS cases with various mutations in different populations. A strong phenotype-genotype correlation, depending on the mutated gene, was observed regarding the type of central nervous system malformation, the frequency of polydactyly, bone dysplasia, and situs inversus. The MKS1 c.1408-35_1408-7del29 intronic mutation was identified in three cases from French or English origin and dated back to 162 generations (approx. 4050 years) ago. We also identified a common MKS3 splice-site mutation, c. INTRODUCTIONMeckel syndrome (MKS; MIM# 249000) is a rare autosomal recessive lethal condition characterized by central nervous system malformations (typically occipital meningoencephalocele), postaxial polydactyly, multicystic kidney dysplasia and ductal proliferation in the portal area of the liver (Mecke and Passarge, 1971). Other malformations frequently include microphthalmia, cleft lip and palate, bowing of long bones, heart defects, and genital anomalies, including micropenis. Complete or partial situs inversus and other laterality defects, such as dextrocardia, have been reported in some cases. MKS is genetically heterogeneous and three loci have been mapped on: 17q23 (MKS1) (Paavola, et al., 1995), 11q14 (MKS2) (Roume, et al., 1998), and 8q24 (MKS3) (Morgan, et al., 2002). Very recently, two genes have been identified: MKS1/FLJ20345 (MIM# 609883) on 17q (Kyttälä, et al., 2006) in endogamous Finnish kindreds, and MKS3/TMEM67 (MIM# 607361) on 8q (Smith, et al., 2006) in consanguineous families from Pakistan and Oman. In 26 Finnish families, the same intronic deletion, c.1408-35_1408-7del29 (called the MKS1-Fin major mutation), was found with a common founder haplotype. Comparative genomics and proteomics data have implicated MKS proteins in primary ciliary and basal body function (Kytällä, et al., 2006;Smith, et al., 2006).In order to evaluate the involvement of MKS1 and MKS3 in Meckel syndrome, and to determine phenotypegenotype correlations and the limits of the phenotypes, we sequenced and/or performed denaturing high performance liquid chromatography (dHPLC) WAVE analysis (Transgenomic Inc.) for both MKS1 and MKS3 in a large multiethnic cohort of 120 independent cases of MKS, each diagnosed by experien...

Ceftriaxone has a higher biliary elimination than cefotaxime (40% versus 10%), which may result in a more pronounced impact on the intestinal microbiota. We performed a monocenter, randomized open-label clinical trial in 22 healthy volunteers treated by intravenous ceftriaxone (1 g/24 h) or cefotaxime (1 g/8 h) for 3 days. We collected fecal samples for phenotypic analyses, 16S rRNA gene profiling, and measurement of the antibiotic concentration and compared the groups for the evolution of microbial counts and indices of bacterial diversity over time. Plasma samples were drawn at day 3 for pharmacokinetic analysis. The emergence of 3rd-generation-cephalosporin-resistant Gram-negative enteric bacilli (Enterobacterales), Enterococcus spp., or noncommensal microorganisms was not significantly different between the groups. Both antibiotics reduced the counts of total Gram-negative enteric bacilli and decreased the bacterial diversity, but the differences between the groups were not significant. All but one volunteer from each group exhibited undetectable levels of antibiotic in feces. Plasma pharmacokinetic endpoints were not correlated to alteration of the bacterial diversity of the gut. Both antibiotics markedly impacted the intestinal microbiota, but no significant differences were detected when standard clinical doses were administered for 3 days. This might be related to the similar daily amounts of antibiotics excreted through the bile using a clinical regimen. (This study has been registered at ClinicalTrials.gov under identifier NCT02659033.)