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Lysogenic induction ends the stable association between a bacteriophage and its host, and the transition to the lytic cycle begins with early prophage e xcision followed by DNA r eplication and p ackaging (ERP). This temporal program is considered universal for P22-like temperate phages, though there is no direct evidence to support the timing and sequence of these events. Here we report that the long-standing ERP program is an observation of the experimentally favored Salmonella phage P22 ts c 2 29 heat-inducible mutant, and that wild-type P22 actually follows the replication-packaging-excision (RPE) program. We find that P22 ts c 2 29 excises early after induction, but P22 delays excision to just before it is detrimental to phage production. This allows P22 to engage in lateral transduction. Thus, at minimal expense to itself, P22 has tuned the timing of excision to balance propagation with lateral transduction, powering the evolution of its host through gene transfer in the interest of self-preservation. During the transition from lysogeny (a stable association between a phage and its bacterial host) to the lytic cycle, prophage excision can be followed or preceded by DNA replication and packaging. Here, the authors show that prophage excision is delayed in Salmonella phage P22, thus allowing the packaging and transfer of large fragments of host DNA via lateral transduction.

Bacteriophages are the main vehicle for gene swapping in bacteria, notoriously of pathogenicity islands and antibiotic resistance genes. Chen et al. noticed that the Staphylococcus aureus prophages do not excise from their host's genome until very late in their life cycles (see the Perspective by Davidson). Thus, the phage DNA is amplified while embedded in the bacterial chromosome. The resulting concatemers are processively packed into virus capsules while still integrated in the host chromosome. Each virion is only set loose when the capsule has reached physical capacity—a process called “headful” packaging. In situ amplification maximizes viral replication, and the headful mechanism means adjacent bacterial-host DNA also gets grabbed to fill the capsule. This process ensures that host genes are transmitted along with the phage. Science , this issue p. 207 ; see also p. 152 Staphylococcus aureus phages amplify and package while chromosomally integrated such that host DNA becomes incorporated in the virus particle. 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.

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.

Although the composition and functional potential of the human gut microbiota evolve over the lifespan, kinship has been identified as a key covariate of microbial community diversification. However, to date, sharing of microbiota features within families has mostly been assessed between parents and their direct offspring. Here we investigate the potential transmission and persistence of familial microbiome patterns and microbial genotypes in a family cohort ( n  = 102) spanning 3 to 5 generations over the same female bloodline. We observe microbiome community composition associated with kinship, with seven low abundant genera displaying familial distribution patterns. While kinship and current cohabitation emerge as closely entangled variables, our explorative analyses of microbial genotype distribution and transmission estimates point at the latter as a key covariate of strain dissemination. Highest potential transmission rates are estimated between sisters and mother–daughter pairs, decreasing with increasing daughter’s age and being higher among cohabiting pairs than those living apart. Although rare, we detect potential transmission events spanning three and four generations, primarily involving species of the genera Alistipes and Bacteroides . Overall, while our analyses confirm the existence of family-bound microbiome community profiles, transmission or co-acquisition of bacterial strains appears to be strongly linked to cohabitation. Quantitative metagenomic analyses of gut microbiomes reveals kinship, together with current cohabitation, as drivers of microbial community transmission and persistence between family members over three to five generations.

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 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 an association between human host genotype and gut microbiome variation. We also suggest that interpretation of applied analyses using genetic associations is complicated by the probable overlap between genetic contributions and heritable components of host environment. Using faecal 16S ribosomal RNA gene sequences and host genotype data from the Flemish Gut Flora Project ( n  = 2,223) and two German cohorts (FoCus, n  = 950; PopGen, n  = 717), we identify genetic associations involving multiple microbial traits. Two of these associations achieved a study-level threshold of P  = 1.57 × 10 −10 ; an association between Ruminococcus and rs150018970 near RAPGEF1 on chromosome 9, and between Coprococcus and rs561177583 within LINC01787 on chromosome 1. Exploratory analyses were undertaken using 11 other genome-wide associations with strong evidence for association ( P  < 2.5 × 10 −8 ) and a previously reported signal of association between rs4988235 ( MCM6 / LCT ) and Bifidobacterium . Across these 14 single-nucleotide polymorphisms there was evidence of signal overlap with other genome-wide association studies, including those for age at menarche and cardiometabolic traits. Mendelian randomization analysis was able to estimate associations between microbial traits 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 catalogue of genetic associations that 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. A microbiome genome-wide association study using three large European cohorts identified several significant study-wide and genome-wide correlations between human genetic variants and microbial traits, and used Mendelian randomization to estimate causal relationships between microbial traits and disease.

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. A population-genomic analysis of more than 800 isolates of Staphylococcus aureus , representing the breadth of host-species diversity, reveals details of the pathogen’s evolutionary trajectory, including how this has been influenced by animal domestication and antibiotic use.

Background Novel strategies for anaerobic bacterial isolations from human faecal samples and various initiatives to generate culture collections of gut-derived bacteria have instigated considerable interest for the development of novel microbiota-based treatments. Early in the process of building a culture collection, optimal faecal sample preservation is essential to safeguard the viability of the broadest taxonomic diversity range possible. In contrast to the much more established faecal storage conditions for meta-omics applications, the impact of stool sample preservation conditions on bacterial growth recovery and isolation remains largely unexplored. In this study, aliquoted faecal samples from eleven healthy human volunteers selected based on a range of physicochemical and microbiological gradients were cryopreserved at – 80 °C either without the addition of any medium (dry condition) or in different Cary-Blair medium conditions with or without a cryoprotectant, i.e. 20% (v/v) glycerol or 5% (v/v) DMSO. Faecal aliquots were subjected to bulk 16S rRNA gene sequencing as well as dilution plating on modified Gifu Anaerobic Medium after preservation for culturable fraction profiling and generation of bacterial culture collections. Results Analyses of compositional variation showed that cryopreservation medium conditions affected quantitative recovery but not the overall community composition of cultured fractions. Post-preservation sample dilution and richness of the uncultured source samples were the major drivers of the cultured fraction richness at genus level. However, preservation conditions differentially affected recovery of specific genera. Presence-absence analysis indicated that twenty-two of the 45 most abundant common genera (>0.01% abundance, dilution 10 −4 ) were recovered in cultured fractions from all preservation conditions, while nine genera were only detected in fractions from a single preservation condition. Overall, the highest number of common genera (i.e. 35/45) in cultured fractions were recovered from sample aliquots preserved without medium and in the presence of Cary-Blair medium containing 5% (v/v) DMSO. Also, in the culture collection generated from the cultured fractions, these two preservation conditions yielded the highest species richness (72 and 66, respectively). Conclusion Our results demonstrate that preservation methods partly determine richness and taxonomic diversity of gut anaerobes recovered from faecal samples. Complementing the current standard practice of cryopreserving stool samples in dry conditions with other preservation conditions, such as Cary-Blair medium with DMSO, could increase the species diversity of gut-associated culture collections. 5AZP4afEVR163YDfjLx79n Video abstract