No abstract

The capacity for some pathogens to jump into different host-species populations is a major threat to public health and food security. Staphylococcus aureus is a multi-host bacterial pathogen responsible for important human and livestock diseases. Here, using a population-genomic approach, we identify humans as a major hub for ancient and recent S. aureus host-switching events linked to the emergence of endemic livestock strains, and cows as the main animal reservoir for the emergence of human epidemic clones. Such host-species transitions are associated with horizontal acquisition of genetic elements from host-specific gene pools conferring traits required for survival in the new host-niche. Importantly, genes associated with antimicrobial resistance are unevenly distributed among human and animal hosts, reflecting distinct antibiotic usage practices in medicine and agriculture. In addition to gene acquisition, genetic diversification has occurred in pathways associated with nutrient acquisition, implying metabolic remodelling after a host switch in response to distinct nutrient availability. For example, S. aureus from dairy cattle exhibit enhanced utilization of lactose-a major source of carbohydrate in bovine milk. Overall, our findings highlight the influence of human activities on the multi-host ecology of a major bacterial pathogen, underpinned by horizontal gene transfer and core genome diversification.

Genetic transduction is a major evolutionary force that underlies bacterial adaptation. Here we report that the temperate bacteriophages of Staphylococcus aureus engage in a distinct form of transduction we term lateral transduction. Staphylococcal prophages do not follow the previously described excision-replication-packaging pathway but instead excise late in their lytic program. Here, DNA packaging initiates in situ from integrated prophages, and large metameric spans including several hundred kilobases of the S. aureus genome are packaged in phage heads at very high frequency. In situ replication before DNA packaging creates multiple prophage genomes so that lateral-transducing particles form during normal phage maturation, transforming parts of the S. aureus chromosome into hypermobile regions of gene transfer.

Recent population-based 1-4 and clinical studies 5 have identified a range of factors associated with human gut microbiome variation. Murine quantitative trait loci 6 , human twin studies 7 and microbiome genome-wide association studies (mGWAS) 1,3,8-12 have provided evidence for genetic contributions to microbiome composition. Despite this, there is still poor overlap in genetic association across human studies. Using appropriate taxon-specific models along with support from independent cohorts, we show association between human host genotype and gut microbiome variation. We also suggest that interpretation of applied analyses using genetic associations is complicated by the likely overlap between genetic contributions and heritable components of host environment. Using fecal derived 16S rRNA gene sequences and host genotype data from the Flemish Gut Flora Project (FGFP, n=2223) and two German cohorts (FoCus, n=950, PopGen n=717), we identify genetic associations involving multiple microbial traits (MTs). Two of these associations achieved a study-level p-value threshold of 1.57x10−10; an association between Ruminococcus and rs150018970 near RAPGEF1 on chromosome 9, and between Coprococcus and rs561177583 within LINC01787 on chromosome 1. Exploratory analysis was undertaken using 11 other genomewide associations with strong evidence for association (p-value < 2.5x10 −08) and a previously reported signal of association between rs4988235 (MCM6/LCT) and Bifidobacterium. Across these 14 SNPs there was evidence of signal overlap with other GWAS including those for age at menarche and cardiometabolic traits. Mendelian randomization (MR) analysis was able to estimate associations between MTs and disease (including Bifidobacterium and body composition), however in the absence of clear microbiome driven effects, caution is needed in interpretation. Overall, this work marks a growing catalog of genetic associations which will provide insight into the contribution of host genotype to gut microbiome. Despite this, the uncertain origin of association signals will likely complicate future work looking to dissect function or use associations for causal inference analysis. Main Human host-microbiome mGWAS are still in their infancy and feature a paucity of overlap for even the most compelling signals across studies 13. This is an observation influenced by environmental variables dominating microbial trait variation 1 and the complications of variation in sample collection, storage conditions, DNA extraction method, PCR primers, and amplicon versus shotgun sequencing 14. While recent advances are Postdoctoral Fellowship (1221620N). SVS is supported by Marie Curie Actions FP7 People

Endophytic microorganisms live inside plants for at least part of their life cycle. According to their life strategies, bacterial endophytes can be classified as “obligate” or “facultative”. Reports that members of the genus Micromonospora, Gram-positive Actinobacteria, are normal occupants of nitrogen-fixing nodules has opened up a question as to what is the ecological role of these bacteria in interactions with nitrogen-fixing plants and whether it is in a process of adaptation from a terrestrial to a facultative endophytic life. The aim of this work was to analyse the genome sequence of Micromonospora lupini Lupac 08 isolated from a nitrogen fixing nodule of the legume Lupinus angustifolius and to identify genomic traits that provide information on this new plant-microbe interaction. The genome of M. lupini contains a diverse array of genes that may help its survival in soil or in plant tissues, while the high number of putative plant degrading enzyme genes identified is quite surprising since this bacterium is not considered a plant-pathogen. Functionality of several of these genes was demonstrated in vitro, showing that Lupac 08 degraded carboxymethylcellulose, starch and xylan. In addition, the production of chitinases detected in vitro, indicates that strain Lupac 08 may also confer protection to the plant. Micromonospora species appears as new candidates in plant-microbe interactions with an important potential in agriculture and biotechnology. The current data strongly suggests that a beneficial effect is produced on the host-plant.

Human milk represents a source of bacteria for the initial establishment of the oral (and gut) microbiomes in the breastfed infant, however, the origin of bacteria in human milk remains largely unknown. While some evidence points towards a possible endogenous enteromammary route, other authors have suggested that bacteria in human milk are contaminants from the skin or the breastfed infant mouth. In this work 16S rRNA sequencing and bacterial culturing and isolation was performed to analyze the microbiota on maternal precolostrum samples, collected from pregnant women before delivery, and on oral samples collected from the corresponding infants. The structure of both ecosystems demonstrated a high proportion of taxa consistently shared among ecosystems, Streptococcus spp. and Staphylococcus spp. being the most abundant. Whole genome sequencing on those isolates that, belonging to the same species, were isolated from both the maternal and infant samples in the same mother-infant pair, evidenced that in 8 out of 10 pairs both isolates were >99.9% identical at nucleotide level. The presence of typical oral bacteria in precolostrum before contact with the newborn indicates that they are not a contamination from the infant, and suggests that at least some oral bacteria reach the infant’s mouth through breastfeeding.

AbstractTo study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed whole-genome genotypes and 16S fecal microbiome data from 18,473 individuals (25 cohorts). Microbial composition showed high variability across cohorts: we detected only 9 out of 410 genera in more than 95% of the samples. A genome-wide association study (GWAS) of host genetic variation in relation to microbial taxa identified 30 loci affecting microbome taxa at a genome-wide significant (P<5×10-8) threshold. Just one locus, the lactase (LCT) gene region, reached study-wide significance (GWAS signal P=8.6×10−21); it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.94×10−10<P<5×10−8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization analyses identified enrichment of microbiome trait loci SNPs in the metabolic, nutrition and environment domains and indicated food preferences and diseases as mediators of genetic effects.

Summary Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p ≤ 5.0 × 10 −8 ). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndromes and the response to their pharmacological treatment. The genetic architecture of stool frequency correlates with that of IBS, and UK Biobank participants from the top 1% of stool frequency polygenic score distribution were associated with 5× higher risk of IBS with diarrhea. These findings pave the way for the identification of actionable pathological mechanisms in IBS and the dysmotility syndromes.