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The open sharing of genomic data provides an incredibly rich resource for the study of bacterial evolution and function and even anthropogenic activities such as the widespread use of antimicrobials. However, these data consist of genomes assembled with different tools and levels of quality checking, and of large volumes of completely unprocessed raw sequence data. In both cases, considerable computational effort is required before biological questions can be addressed. Here, we assembled and characterised 661,405 bacterial genomes retrieved from the European Nucleotide Archive (ENA) in November of 2018 using a uniform standardised approach. Of these, 311,006 did not previously have an assembly. We produced a searchable COmpact Bit-sliced Signature (COBS) index, facilitating the easy interrogation of the entire dataset for a specific sequence (e.g., gene, mutation, or plasmid). Additional MinHash and pp-sketch indices support genome-wide comparisons and estimations of genomic distance. Combined, this resource will allow data to be easily subset and searched, phylogenetic relationships between genomes to be quickly elucidated, and hypotheses rapidly generated and tested. We believe that this combination of uniform processing and variety of search/filter functionalities will make this a resource of very wide utility. In terms of diversity within the data, a breakdown of the 639,981 high-quality genomes emphasised the uneven species composition of the ENA/public databases, with just 20 of the total 2,336 species making up 90% of the genomes. The overrepresented species tend to be acute/common human pathogens, aligning with research priorities at different levels from individual interests to funding bodies and national and global public health agencies.

We aimed to clarify the epidemiologic and clinical importance of evolutionary events that occurred in carbapenem-resistant Klebsiella pneumoniae (CRKP). We collected 203 CRKP causing bloodstream infections in a tertiary hospital in China during 2013-2017. We detected a subclonal shift in the dominant clone sequence type (ST) 11 CRKP in which the previously prevalent capsular loci (KL) 47 had been replaced by KL64 since 2016. Patients infected with ST11-KL64 CRKP had a significantly higher 30-day mortality rate than other CRKP-infected patients. Enhanced virulence was further evidenced by phenotypic tests. Phylogenetic reconstruction demonstrated that ST11-KL64 is derived from an ST11-KL47-like ancestor through recombination. We identified a pLVPK-like virulence plasmid carrying rmpA and peg-344 in ST11-KL64 exclusively from 2016 onward. The pLVPK-like-positive ST11-KL64 isolates exhibited enhanced environmental survival. Retrospective screening of a national collection identified ST11-KL64 in multiple regions. Targeted surveillance of this high-risk CRKP clone is urgently needed.

Source of current cholera epidemic Cholera has affected human populations for centuries, and the agent responsible, Vibrio cholerae , continues to infect millions each year. Using whole genome phylogeny, it is now shown that the current seventh epidemic originated in the Bay of Bengal in the 1950s and has spread through the world in three independent waves. Vibrio cholerae is a globally important pathogen that is endemic in many areas of the world and causes 3–5 million reported cases of cholera every year. Historically, there have been seven acknowledged cholera pandemics; recent outbreaks in Zimbabwe and Haiti are included in the seventh and ongoing pandemic 1 . Only isolates in serogroup O1 (consisting of two biotypes known as ‘classical’ and ‘El Tor’) and the derivative O139 (refs 2 , 3 ) can cause epidemic cholera 2 . It is believed that the first six cholera pandemics were caused by the classical biotype, but El Tor has subsequently spread globally and replaced the classical biotype in the current pandemic 1 . Detailed molecular epidemiological mapping of cholera has been compromised by a reliance on sub-genomic regions such as mobile elements to infer relationships, making El Tor isolates associated with the seventh pandemic seem superficially diverse. To understand the underlying phylogeny of the lineage responsible for the current pandemic, we identified high-resolution markers (single nucleotide polymorphisms; SNPs) in 154 whole-genome sequences of globally and temporally representative V. cholerae isolates. Using this phylogeny, we show here that the seventh pandemic has spread from the Bay of Bengal in at least three independent but overlapping waves with a common ancestor in the 1950s, and identify several transcontinental transmission events. Additionally, we show how the acquisition of the SXT family of antibiotic resistance elements has shaped pandemic spread, and show that this family was first acquired at least ten years before its discovery in V. cholerae .

The genus Serratia has been studied for over a century and includes clinically-important and diverse environmental members. Despite this, there is a paucity of genomic information across the genus and a robust whole genome-based phylogenetic framework is lacking. Here, we have assembled and analysed a representative set of 664 genomes from across the genus, including 215 historic isolates originally used in defining the genus. Phylogenomic analysis of the genus reveals a clearly-defined population structure which displays deep divisions and aligns with ecological niche, as well as striking congruence between historical biochemical phenotyping data and contemporary genomics data. We highlight the genomic, phenotypic and plasmid diversity of Serratia , and provide evidence of different patterns of gene flow across the genus. Our work provides a framework for understanding the emergence of clinical and other lineages of Serratia . The genus Serratia includes clinically-important and diverse environmental bacteria. Here, Williams et al. assemble and analyse a representative set of 664 genomes from across the genus, including historic isolates, to provide a genome-based phylogenetic framework for a better understanding of the emergence of clinical and environmental lineages of Serratia .

Melioidosis is an often-fatal neglected tropical disease caused by an environmental bacterium Burkholderia pseudomallei . However, our understanding of the disease-causing bacterial lineages, their dissemination, and adaptive mechanisms remains limited. To address this, we conduct a comprehensive genomic analysis of 1,391 B. pseudomallei isolates collected from nine hospitals in northeast Thailand between 2015 and 2018, and contemporaneous isolates from neighbouring countries, representing the most densely sampled collection to date. Our study identifies three dominant lineages, each with unique gene sets potentially enhancing bacterial fitness in the environment. We find that recombination drives lineage-specific gene flow. Transcriptome analyses of representative clinical isolates from each dominant lineage reveal increased expression of lineage-specific genes under environmental conditions in two out of three lineages. This underscores the potential importance of environmental persistence for these dominant lineages. The study also highlights the influence of environmental factors such as terrain slope, altitude, and river direction on the geographical dispersal of B. pseudomallei . Collectively, our findings suggest that environmental persistence may play a role in facilitating the spread of B. pseudomallei , and as a prerequisite for exposure and infection, thereby providing useful insights for informing melioidosis prevention and control strategies. An environmental bacterium, Burkholderia pseudomallei causes melioidosis, a fatal infection. A study from NE Thailand identifies that dominant lineages carry specific gene sets enhancing environmental persistence.

Key Points The evolution of mammalian pathogenesis in the Yersinia genus has occurred in different lineages in parallel through a balanced mixture of gene gain and gene loss events. Only by sequencing pathogenic and non-pathogenic representatives from an entire bacterial genus can such observations be made. The parallel evolution of pathogenesis is even shared with enteric pathogens outside of the Yersinia genus, notably in the Salmonella genus. Gene loss events lead to niche restriction owing to a reduction in metabolic flexibility, which is often seen in lineages that evolve a more acutely pathogenic phenotype. The potential of loss of fitness from the expression of genes acquired in gene gain events is mediated by the transcriptional silencing of, or fine control of, these acquired elements by ancestral regulons that are regulated by factors such as RovA and H-NS. In the genomics era, Yersinia has proven to be a model genus for studying the emergence of pathogenesis. Focusing on this model, McNally and colleagues highlight the events in genome evolution that underlie pathogenesis and argue for an 'eco–evo' perspective of pathogen evolution. Pathogenic species in the Yersinia genus have historically been targets for research aimed at understanding how bacteria evolve into mammalian pathogens. The advent of large-scale population genomic studies has greatly accelerated the progress in this field, and Yersinia pestis , Yersinia pseudotuberculosis and Yersinia enterocolitica have once again acted as model organisms to help shape our understanding of the evolutionary processes involved in pathogenesis. In this Review, we highlight the gene gain, gene loss and genome rearrangement events that have been identified by genomic studies in pathogenic Yersinia species, and we discuss how these findings are changing our understanding of pathogen evolution. Finally, as these traits are also found in the genomes of other species in the Enterobacteriaceae, we suggest that they provide a blueprint for the evolution of enteropathogenic bacteria.

Key Points All available genome data indicate that the various Shigella spp.have arisen from different ancestral Escherichia coli isolates on several independent occasions. The acquisition of plasmids that encode virulence genes into numerous ancestral Shigella spp. were pivotal in their evolution as human pathogens. The possession and adaptation of these plasmids has shaped the current Shigella spp. Convergent evolution, through the acquisition of mobile elements and loss of gene function, enabled Shigella spp. to become restricted to humans and exquisitely adapted to interact with the human intestinal mucosa. The shift in dominance from Shigella flexneri to Shigella sonnei in economically transitioning nations warrants more in-depth studies of the evolution and epidemiology of these species. There is a correlation between the global dissemination of Shigella spp. clones and acquisition of resistance to multiple antimicrobials. An antimicrobial-resistance phenotype is likely to be advantageous for the bacteria, as it would promote post-symptomatic shedding by the host and would sustain short-term transmission. In comparison to S. sonnei and S. flexneri , comparatively little is currently understood about Shigella dysenteriae and Shigella boydii ; this needs to be addressed to reveal the full evolutionary landscape of the genus. Future laboratory research should be combined with genomics to address the survival, transmission and evolution of Shigella spp. in the environment, specifically focusing on how the environmental lifestyle can affect disease epidemiology and global public health. Shigella spp. harbour an arsenal of virulence factors that enable host invasion. Here, Baker and colleagues review how these bacteria have evolved from Escherichia coli on several occasions into highly specialized, human-restricted pathogens that have spread globally. Shigella spp. are some of the key pathogens responsible for the global burden of diarrhoeal disease. These facultative intracellular bacteria belong to the family Enterobacteriaceae, together with other intestinal pathogens, such as Escherichia coli and Salmonella spp. The genus Shigella comprises four different species, each consisting of several serogroups, all of which show phenotypic similarity, including invasive pathogenicity. DNA sequencing suggests that this similarity results from the convergent evolution of different Shigella spp. founders. Here, we review the evolutionary relationships between Shigella spp. and E . coli , and we highlight how the genomic plasticity of these bacteria and their acquisition of a distinctive virulence plasmid have enabled the development of such highly specialized pathogens. Furthermore, we discuss the insights that genotyping and whole-genome sequencing have provided into the phylogenetics and intercontinental spread of Shigella spp.

RNA sequencing provides a new perspective on the genome of Mycobacterium tuberculosis by revealing an extensive presence of non-coding RNA, including long 5' and 3' untranslated regions, antisense transcripts, and intergenic small RNA (sRNA) molecules. More than a quarter of all sequence reads mapping outside of ribosomal RNA genes represent non-coding RNA, and the density of reads mapping to intergenic regions was more than two-fold higher than that mapping to annotated coding sequences. Selected sRNAs were found at increased abundance in stationary phase cultures and accumulated to remarkably high levels in the lungs of chronically infected mice, indicating a potential contribution to pathogenesis. The ability of tubercle bacilli to adapt to changing environments within the host is critical to their ability to cause disease and to persist during drug treatment; it is likely that novel post-transcriptional regulatory networks will play an important role in these adaptive responses.

Background. Klebsiella pneumoniae is an opportunistic pathogen and leading cause of hospital-associated infections. Intensive care unit (ICU) patients are particularly at risk. Klebsiella pneumoniae is part of the healthy human microbiome, providing a potential reservoir for infection. However, the frequency of gut colonization and its contribution to infections are not well characterized. Methods. We conducted a 1-year prospective cohort study in which 498 ICU patients were screened for rectal and throat carriage of K. pneumoniae shortly after admission. Klebsiella pneumoniae isolated from screening swabs and clinical diagnostic samples were characterized using whole genome sequencing and combined with epidemiological data to identify likely transmission events. Results. Klebsiella pneumoniae carriage frequencies were estimated at 6% (95% confidence interval [CI], 3%–8%) among ICU patients admitted direct from the community, and 19% (95% CI, 14%–51%) among those with recent healthcare contact. Gut colonization on admission was significantly associated with subsequent infection (infection risk 16% vs 3%, odds ratio [OR] = 6.9, P < .001), and genome data indicated matching carriage and infection isolates in 80% of isolate pairs. Five likely transmission chains were identified, responsible for 12% of K. pneumoniae infections in ICU. In sum, 49% of K. pneumoniae infections were caused by the patients' own unique strain, and 48% of screened patients with infections were positive for prior colonization. Conclusions. These data confirm K. pneumoniae colonization is a significant risk factor for infection in ICU, and indicate ∼50% of K. pneumoniae infections result from patients' own microbiota. Screening for colonization on admission could limit risk of infection in the colonized patient and others.

Significance Common features have been observed in the genome sequences of bacterial pathogens that infect few hosts. These “host adaptations” include the acquisition of pathogenicity islands of multiple genes involved in disease, losses of whole genes, and even single mutations that affect gene function. Within Salmonella enterica is a natural model system of four pathogens that are each other’s closest relatives, including a host-generalist, two host-specialists, and one with strong host associations. With whole-genome sequences, we aimed to improve our understanding of the number, nature, and order of these host adaptation events, shedding light on how human and animal pathogens arose in the past, and potentially allowing us to predict how emerging pathogens will evolve in the future. Many bacterial pathogens are specialized, infecting one or few hosts, and this is often associated with more acute disease presentation. Specific genomes show markers of this specialization, which often reflect a balance between gene acquisition and functional gene loss. Within Salmonella enterica subspecies enterica , a single lineage exists that includes human and animal pathogens adapted to cause infection in different hosts, including S. enterica serovar Enteritidis (multiple hosts), S. Gallinarum (birds), and S. Dublin (cattle). This provides an excellent evolutionary context in which differences between these pathogen genomes can be related to host range. Genome sequences were obtained from ∼60 isolates selected to represent the known diversity of this lineage. Examination and comparison of the clades within the phylogeny of this lineage revealed signs of host restriction as well as evolutionary events that mark a path to host generalism. We have identified the nature and order of events for both evolutionary trajectories. The impact of functional gene loss was predicted based upon position within metabolic pathways and confirmed with phenotyping assays. The structure of S. Enteritidis is more complex than previously known, as a second clade of S. Enteritidis was revealed that is distinct from those commonly seen to cause disease in humans or animals, and that is more closely related to S. Gallinarum. Isolates from this second clade were tested in a chick model of infection and exhibited a reduced colonization phenotype, which we postulate represents an intermediate stage in pathogen–host adaptation.