Unique genomic sequences in a novel Mycobacterium avium subsp. hominissuis lineage enable fine scale transmission route tracing during pig movement.

Mycobacterium avium subsp. hominissuis (MAH) is one of the most prevalent mycobacteria causing non-tuberculous mycobacterial disease in humans and animals. Of note, MAH is a major cause of mycobacterial granulomatous mesenteric lymphadenitis outbreaks in pig populations. To determine the precise source of infection of MAH in a pig farm and to clarify the epidemiological relationship among pig, human and environmental MAH lineages, we collected 50 MAH isolates from pigs reared in Japan and determined draft genome sequences of 30 isolates. A variable number of tandem repeat analysis revealed that most pig MAH isolates in Japan were closely related to North American, European and Russian human isolates but not to those from East Asian human and their residential environments. Historical recombination analysis revealed that most pig isolates could be classified into SC2/4 and SC3, which contain MAH isolated from pig, European human and environmental isolates. Half of the isolates in SC2/4 had many recombination events with MAH lineages isolated from humans in East Asia. To our surprise, four isolates belonged to a new lineage (SC5) in the global MAH population. Members of SC5 had few footprints of inter-lineage recombination in the genome, and carried 80 unique genes, most of which were located on lineage specific-genomic islands. Using unique genetic features, we were able to trace the putative transmission route via their host pigs. Together, we clarify the possibility of species-specificity of MAH in addition to local adaptation. Our results highlight two transmission routes of MAH, one exposure on pig farms from the environment and the other via pig movement. Moreover, our study also warns that the evolution of MAH in pigs is influenced by MAH from patients and their residential environments, even if the MAH are genetically distinct.

Comprehensive Genome Analysis of Neisseria meningitidis from South America Reveals a Distinctive Pathogenicity-Related Prophage Repertoire.

Neisseria meningitidis, a bacterium that colonizes in the human nasopharynx, occasionally causes invasive meningococcal disease leading to meningitis or septicemia. Different serogroups and lineages (clonal complexes) are related to the occurrence and epidemiology of N. meningitidis. Despite vaccines for most serogroups, N. meningitidis lineages causing unusual clinical manifestations and a higher fatality rate compared to other lineages have been reported in South America. The present study focused on exploring the diversity of N. meningitidis prophages from South America and their relationship with the epidemiological variables of these strains. We found a high diversity of prophages among the different clonal complexes. By comparing them with previously described N. meningitidis phages and prophages, we revealed groups of prophages sharing similar compositions, which could be useful for prophage comparison in N. meningitidis. Furthermore, we observed a high correlation between the prophage content and epidemiological features, e.g., pathogenicity or clonal complex. Additionally, a distinctive filamentous prophage named here as IMSAR-11 (Invasive Meningococci from South America Related to cc11) was identified. Interestingly, two versions of IMSAR-11, circular and chromosomally integrated, were found. Overall, this study reinforces the importance of the genomic characterization of circulating N. meningitidis lineages to generate new targets for lineage monitoring, diagnosis, or appropriateness of vaccine development. Further studies are necessary to understand the role of these prophages in the persistence, dispersal, and virulence of N. meningitidis in the world.

A Standardized Procedure for Monitoring Harmful Algal Blooms in Chile by Metabarcoding Analysis.

Harmful algae blooms (HABs) monitoring has been implemented worldwide, and Chile, a country famous for its fisheries and aquaculture, has intensively used microscopic and toxin analyses for decades for this purpose. Molecular biological methods, such as high-throughput DNA sequencing and bacterial assemblage-based approaches, are just beginning to be introduced in Chilean HAB monitoring, and the procedures have not yet been standardized. Here, 16S rRNA and 18S rRNA metabarcoding analyses for monitoring Chilean HABs are introduced stepwise. According to a recent hypothesis, algal-bacterial mutualistic association plays a critical synergetic or antagonistic relationship accounting for bloom initiation, maintenance, and regression. Thus, monitoring HAB from algal-bacterial perspectives may provide a broader understanding of HAB mechanisms and the basis for early warning. Metabarcoding analysis is one of the best suited molecular-based tools for this purpose because it can detect massive algal-bacterial taxonomic information in a sample. The visual procedures of sampling to metabarcoding analysis herein provide specific instructions, aiming to reduce errors and collection of reliable data.

Capsular polysaccharide switching in Streptococcus suis modulates host cell interactions and virulence.

The capsular polysaccharide (CPS) of Streptococcus suis defines various serotypes based on its composition and structure. Though serotype switching has been suggested to occur between S. suis strains, its impact on pathogenicity and virulence remains unknown. Herein, we experimentally generated S. suis serotype-switched mutants from a serotype 2 strain that express the serotype 3, 4, 7, 8, 9, or 14 CPS. The effects of serotype switching were then investigated with regards to classical properties conferred by presence of the serotype 2 CPS, including adhesion to/invasion of epithelial cells, resistance to phagocytosis by macrophages, killing by whole blood, dendritic cell-derived pro-inflammatory mediator production and virulence using mouse and porcine infection models. Results demonstrated that these properties on host cell interactions were differentially modulated depending on the switched serotypes, although some different mutations other than loci of CPS-related genes were found in each the serotype-switched mutant. Among the serotype-switched mutants, the mutant expressing the serotype 8 CPS was hyper-virulent, whereas mutants expressing the serotype 3 or 4 CPSs had reduced virulence. By contrast, switching to serotype 7, 9, or 14 CPSs had little to no effect. These findings suggest that serotype switching can drastically alter S. suis virulence and host cell interactions.

Genomic features of Mycobacterium avium subsp. hominissuis isolated from pigs in Japan.

Mycobacterium avium subsp. hominissuis (MAH) is one of the most important agents causing non-tuberculosis mycobacterial infection in humans and pigs. There have been advances in genome analysis of MAH from human isolates, but studies of isolates from pigs are limited despite its potential source of infection to human. Here, we obtained 30 draft genome sequences of MAH from pigs reared in Japan. The 30 draft genomes were 4,848,678-5,620,788 bp in length, comprising 4652-5388 coding genes and 46-75 (median: 47) tRNAs. All isolates had restriction modification-associated genes and 185-222 predicted virulence genes. Two isolates had tRNA arrays and one isolate had a clustered regularly interspaced short palindromic repeat (CRISPR) region. Our results will be useful for evaluation of the ecology of MAH by providing a foundation for genome-based epidemiological studies.

Protocols for Monitoring Harmful Algal Blooms for Sustainable Aquaculture and Coastal Fisheries in Chile.

Harmful algae blooms (HABs) cause acute effects on marine ecosystems due to their production of endogenous toxins or their enormous biomass, leading to significant impacts on local economies and public health. Although HAB monitoring has been intensively performed at spatiotemporal scales in coastal areas of the world over the last decades, procedures have not yet been standardized. HAB monitoring procedures are complicated and consist of many methodologies, including physical, chemical, and biological water sample measurements. Each monitoring program currently uses different combinations of methodologies depending on site specific purposes, and many prior programs refer to the procedures in quotations. HAB monitoring programs in Chile have adopted the traditional microscopic and toxin analyses but not molecular biology and bacterial assemblage approaches. Here we select and optimize the HAB monitoring methodologies suitable for Chilean geography, emphasizing on metabarcoding analyses accompanied by the classical tools with considerations including cost, materials and instrument availability, and easiness and efficiency of performance. We present results from a pilot study using the standardized stepwise protocols, demonstrating feasibility and plausibility for sampling and analysis for the HAB monitoring. Such specific instructions in the standardized protocol are critical obtaining quality data under various research environments involving multiple stations, different analysts, various time-points, and long HAB monitoring duration.

Single-Cell Genomics of Novel Actinobacteria With the Wood-Ljungdahl Pathway Discovered in a Serpentinizing System.

Serpentinite-hosted systems represent modern-day analogs of early Earth environments. In these systems, water-rock interactions generate highly alkaline and reducing fluids that can contain hydrogen, methane, and low-molecular-weight hydrocarbons-potent reductants capable of fueling microbial metabolism. In this study, we investigated the microbiota of Hakuba Happo hot springs (∼50°C; pH∼10.5-11), located in Nagano (Japan), which are impacted by the serpentinization process. Analysis of the 16S rRNA gene amplicon sequences revealed that the bacterial community comprises Nitrospirae (47%), "Parcubacteria" (19%), Deinococcus-Thermus (16%), and Actinobacteria (9%), among others. Notably, only 57 amplicon sequence variants (ASV) were detected, and fifteen of these accounted for 90% of the amplicons. Among the abundant ASVs, an early-branching, uncultivated actinobacterial clade identified as RBG-16-55-12 in the SILVA database was detected. Ten single-cell genomes (average pairwise nucleotide identity: 0.98-1.00; estimated completeness: 33-93%; estimated genome size: ∼2.3 Mb) that affiliated with this clade were obtained. Taxonomic classification using single copy genes indicates that the genomes belong to the actinobacterial class-level clade UBA1414 in the Genome Taxonomy Database. Based on metabolic pathway predictions, these actinobacteria are anaerobes, capable of glycolysis, dissimilatory nitrate reduction and CO2 fixation via the Wood-Ljungdahl (WL) pathway. Several other genomes within UBA1414 and two related class-level clades also encode the WL pathway, which has not yet been reported for the Actinobacteria phylum. For the Hakuba actinobacterium, the energy metabolism related to the WL pathway is likely supported by a combination of the Rnf complex, group 3b and 3d [NiFe]-hydrogenases, [FeFe]-hydrogenases, and V-type (H+/Na+ pump) ATPase. The genomes also harbor a form IV ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO) complex, also known as a RubisCO-like protein, and contain signatures of interactions with viruses, including clustered regularly interspaced short palindromic repeat (CRISPR) regions and several phage integrases. This is the first report and detailed genome analysis of a bacterium within the Actinobacteria phylum capable of utilizing the WL pathway. The Hakuba actinobacterium is a member of the clade UBA1414/RBG-16-55-12, formerly within the group "OPB41." We propose to name this bacterium 'Candidatus Hakubanella thermoalkaliphilus.'

Continuation and replacement of Vibrio cholerae non-O1 clonal genomic groups isolated from Plecoglossus altivelis fish in freshwaters.

The dissemination and abundances of Vibrio species in aquatic environments are of interest, as some species cause emerging diseases in humans and in aquatic organisms like fish. It is suggested that Vibrio cholerae non-O1 infections of Plecoglossus altivelis ('ayu') were spread to various parts of Japan through the annual transplantation of juvenile fish. To investigate this, we used genome-aided tracing of 17 V. cholerae strains isolated from ayu between the 1970s and 1990s in different Japanese freshwater systems. The strains formed a genomic clade distinct from all known clades, which we designate as the Ayu clade. Two clonal genomic groups identified within the clade, Ayu-1 and Ayu-2, persisted for a few years (between 1977 to 1979 and 1987 to 1990, respectively), and clonal replacement of Ayu-1 by Ayu-2 took place over an 8-year period. Despite the high similarity between Ayu-1 and Ayu-2 (> 99.9% identity and > 97% fraction of genomes shared), differences in their gene repertoires were found, raising the possibility that they are phenotypically distinct. These results highlight the importance of genome-based studies for understanding the long-term dynamics of populations over the timescale of years.

Draft genome sequences of Mycolicibacterium peregrinum isolated from a pig with lymphadenitis and from soil on the same Japanese pig farm.

OBJECTIVES: Mycolicibacterium peregrinum, a rapidly growing mycobacterial species, can opportunistically infect humans and other animals. Although M. peregrinum infections in animals have been reported, the infection sources are unknown, as is information on its virulence and drug resistant genes, which limits our current understanding of this bacterium. To address this knowledge gap, we obtained draft genome sequences for two M. peregrinum isolates; one from a case of pig lymphadenitis and one from the pig farm's soil. DATA DESCRIPTION: We report here the draft genome sequences of M. peregrinum isolates 131_1 and 138 (6,451,733-bp and 6,479,047-bp). They were isolated from a pig with mesenteric lymph node lymphadenitis and from soil on the Japanese farm where the pig was reared. A sequence alignment identity score of 100% was obtained by in silico DNA-DNA hybridization of the two isolates, while 98.28% (isolate 131_1) and 98.27% (isolate 138) scores were recorded for hybridization with a human isolate. Both isolates carry arr-1, AAC(2')-Ib, RbpA, mtrA and tap drug-resistance genes. Isolates 131_1 and 138 carry 234 and 236 putative virulence genes, respectively. Therefore, environment M. peregrinum is potentially drug resistant and can cause swine lymphadenitis. Our data provides valuable new information for future studies on nontuberculous mycobacteria.

Draft Genome Sequences of Mycolicibacter senuensis Isolate GF74 and Mycobacterium colombiense Isolates GF28 and GF76 from a Swine Farm in Japan.

Several nontuberculous mycobacteria (NTM) occasionally infect humans and animals. Here, we report the draft genome sequences of Mycolicibacter senuensis isolate GF74 (4,792,997 bp) and Mycobacterium colombiense isolates GF28 and GF76 (5,473,554 bp and 5,426,852 bp, respectively) isolated from a swine farm in Japan. These sequences provide further information on NTM research.

Multi-gene phylogenetic analysis reveals that shochu-fermenting Saccharomyces cerevisiae strains form a distinct sub-clade of the Japanese sake cluster.

Shochu is a traditional Japanese distilled spirit. The formation of the distinguishing flavour of shochu produced in individual distilleries is attributed to putative indigenous yeast strains. In this study, we performed the first (to our knowledge) phylogenetic classification of shochu strains based on nucleotide gene sequences. We performed phylogenetic classification of 21 putative indigenous shochu yeast strains isolated from 11 distilleries. All of these strains were shown or confirmed to be Saccharomyces cerevisiae, sharing species identification with 34 known S. cerevisiae strains (including commonly used shochu, sake, ale, whisky, bakery, bioethanol and laboratory yeast strains and clinical isolate) that were tested in parallel. Our analysis used five genes that reflect genome-level phylogeny for the strain-level classification. In a first step, we demonstrated that partial regions of the ZAP1, THI7, PXL1, YRR1 and GLG1 genes were sufficient to reproduce previous sub-species classifications. In a second step, these five analysed regions from each of 25 strains (four commonly used shochu strains and the 21 putative indigenous shochu strains) were concatenated and used to generate a phylogenetic tree. Further analysis revealed that the putative indigenous shochu yeast strains form a monophyletic group that includes both the shochu yeasts and a subset of the sake group strains; this cluster is a sister group to other sake yeast strains, together comprising a sake-shochu group. Differences among shochu strains were small, suggesting that it may be possible to correlate subtle phenotypic differences among shochu flavours with specific differences in genome sequences. Copyright © 2017 John Wiley & Sons, Ltd.

Complete genome sequence and expression profile of the commercial lytic enzyme producer Lysobacter enzymogenes M497-1.

Lysobacter enzymogenes M497-1 is a producer of commercialized achromopeptidase and is expected to harbour genes encoding various other antimicrobial enzymes. Here, we present the complete sequence of the genome of M497-1 and the expression profiles of the genes for various antimicrobial enzymes. Of the 117 peptidase-encoding genes found in the 6.1-Mb genome of M497-1, 15 genes (aside from the gene encoding the achromopeptidase) were expressed at a level higher than that of the average ribosomal protein genes in the 24-h culture. Thus, the strain was found more valuable than hitherto considered. In addition, M497-1 harbours 98 genes involved in the biosynthesis of various natural products, 16 of which are M497-1-specific across 4 Lysobacter species. A gene cluster starting at LEN_2603 through LEN_2673 among the 98 genes closely resembled the lysobactin biosynthesis gene cluster of Lysobacter sp. ATCC 53042. It is likely that M497-1 may produce lysobactin or related antibacterial compounds. Furthermore, comparative genomic analysis of M497-1 and four other Lysobacter species revealed that their core genome structure comprises 3,737 orthologous groups. Our findings are expected to advance further biotechnological application of Lysobacter spp. as a promising source of natural bioactive compounds.

Complete genome and gene expression analyses of Asaia bogorensis reveal unique responses to culture with mammalian cells as a potential opportunistic human pathogen.

Asaia bogorensis, a member of acetic acid bacteria (AAB), is an aerobic bacterium isolated from flowers and fruits, as well as an opportunistic pathogen that causes human peritonitis and bacteraemia. Here, we determined the complete genomic sequence of the As. bogorensis type strain NBRC 16594, and conducted comparative analyses of gene expression under different conditions of co-culture with mammalian cells and standard AAB culture. The genome of As. bogorensis contained 2,758 protein-coding genes within a circular chromosome of 3,198,265 bp. There were two complete operons encoding cytochrome bo3-type ubiquinol terminal oxidases: cyoABCD-1 and cyoABCD-2. The cyoABCD-1 operon was phylogenetically common to AAB genomes, whereas the cyoABCD-2 operon belonged to a lineage distinctive from the cyoABCD-1 operon. Interestingly, cyoABCD-1 was less expressed under co-culture conditions than under the AAB culture conditions, whereas the converse was true for cyoABCD-2. Asaia bogorensis shared pathogenesis-related genes with another pathogenic AAB, Granulibacter bethesdensis, including a gene coding pathogen-specific large bacterial adhesin and additional genes for the inhibition of oxidation and antibiotic resistance. Expression alteration of the respiratory chain and unique hypothetical genes may be key traits that enable the bacterium to survive under the co-culture conditions.

Low frequency of endospore-specific genes in subseafloor sedimentary metagenomes.

Spore formation is considered to be one of the microbial strategies for long-term survival in subseafloor sedimentary habitats. However, our knowledge of the genetic and physiological characteristics of subseafloor microbes is limited. Here, we studied the distribution and frequency of genes that are related to endospore formation in 10 subseafloor sedimentary metagenomes from Site C9001 off Japan and Site 1229 off Peru. None or very low frequencies of endospore-specific genes (e.g. dpaA, dpaB, sspA, spo0A, spoIIGA, spoIIM, spoIIIAB, spoIVA, spoIVB, yabP, yunB, spoVM) were observed in the subseafloor metagenomes. Based on the number of universally conserved single copy genes, the frequency ratio of putative endospore-formers was estimated to be < 10%, which is consistent with the frequency of Clostridia-derived genomes (2-4%) but is lower than previous estimates based on the concentration of dipicolinic acid. Conceivable explanations for this discrepancy are as follows: the efficiency of lysis and DNA extraction of subseafloor endospore cells may have been lower than those of vegetative cells, conversion factor of dipicolinic acid content per cell may differ, and/or sporulation-related genes and other functional strategies for long-term survival in the deep subseafloor biosphere are evolutionarily distinct from known spore-forming gene repertoires.

High frequency of phylogenetically diverse reductive dehalogenase-homologous genes in deep subseafloor sedimentary metagenomes.

Marine subsurface sediments on the Pacific margin harbor diverse microbial communities even at depths of several hundreds meters below the seafloor (mbsf) or more. Previous PCR-based molecular analysis showed the presence of diverse reductive dehalogenase gene (rdhA) homologs in marine subsurface sediment, suggesting that anaerobic respiration of organohalides is one of the possible energy-yielding pathways in the organic-rich sedimentary habitat. However, primer-independent molecular characterization of rdhA has remained to be demonstrated. Here, we studied the diversity and frequency of rdhA homologs by metagenomic analysis of five different depth horizons (0.8, 5.1, 18.6, 48.5, and 107.0 mbsf) at Site C9001 off the Shimokita Peninsula of Japan. From all metagenomic pools, remarkably diverse rdhA-homologous sequences, some of which are affiliated with novel clusters, were observed with high frequency. As a comparison, we also examined frequency of dissimilatory sulfite reductase genes (dsrAB), key functional genes for microbial sulfate reduction. The dsrAB were also widely observed in the metagenomic pools whereas the frequency of dsrAB genes was generally smaller than that of rdhA-homologous genes. The phylogenetic composition of rdhA-homologous genes was similar among the five depth horizons. Our metagenomic data revealed that subseafloor rdhA homologs are more diverse than previously identified from PCR-based molecular studies. Spatial distribution of similar rdhA homologs across wide depositional ages indicates that the heterotrophic metabolic processes mediated by the genes can be ecologically important, functioning in the organic-rich subseafloor sedimentary biosphere.

Genome-wide survey of mutual homologous recombination in a highly sexual bacterial species.

The nature of a species remains a fundamental and controversial question. The era of genome/metagenome sequencing has intensified the debate in prokaryotes because of extensive horizontal gene transfer. In this study, we conducted a genome-wide survey of outcrossing homologous recombination in the highly sexual bacterial species Helicobacter pylori. We conducted multiple genome alignment and analyzed the entire data set of one-to-one orthologous genes for its global strains. We detected mosaic structures due to repeated recombination events and discordant phylogenies throughout the genomes of this species. Most of these genes including the "core" set of genes and horizontally transferred genes showed at least one recombination event. Taking into account the relationship between the nucleotide diversity and the minimum number of recombination events per nucleotide, we evaluated the recombination rate in every gene. The rate appears constant across the genome, but genes with a particularly high or low recombination rate were detected. Interestingly, genes with high recombination included those for DNA transformation and for basic cellular functions, such as biosynthesis and metabolism. Several highly divergent genes with a high recombination rate included those for host interaction, such as outer membrane proteins and lipopolysaccharide synthesis. These results provide a global picture of genome-wide distribution of outcrossing homologous recombination in a bacterial species for the first time, to our knowledge, and illustrate how a species can be shaped by mutual homologous recombination.

Domain movement within a gene: a novel evolutionary mechanism for protein diversification.

A protein function is carried out by a specific domain localized at a specific position. In the present study, we report that, within a gene, a specific amino acid sequence can move between a certain position and another position. This was discovered when the sequences of restriction-modification systems within the bacterial species Helicobacter pylori were compared. In the specificity subunit of Type I restriction-modification systems, DNA sequence recognition is mediated by target recognition domain 1 (TRD1) and TRD2. To our surprise, several sequences are shared by TRD1 and TRD2 of genes (alleles) at the same locus (chromosomal location); these domains appear to have moved between the two positions. The gene/protein organization can be represented as x-(TRD1)-y-x-(TRD2)-y, where x and y represent repeat sequences. Movement probably occurs by recombination at these flanking DNA repeats. In accordance with this hypothesis, recombination at these repeats also appears to decrease two TRDs into one TRD or increase these two TRDs to three TRDs (TRD1-TRD2-TRD2) and to allow TRD movement between genes even at different loci. Similar movement of domains between TRD1 and TRD2 was observed for the specificity subunit of a Type IIG restriction enzyme. Similar movement of domain between TRD1 and TRD2 was observed for Type I restriction-modification enzyme specificity genes in two more eubacterial species, Streptococcus pyogenes and Mycoplasma agalactiae. Lateral domain movements within a protein, which we have designated DOMO (domain movement), represent novel routes for the diversification of proteins.

Evolution in an oncogenic bacterial species with extreme genome plasticity: Helicobacter pylori East Asian genomes.

BACKGROUND: The genome of Helicobacter pylori, an oncogenic bacterium in the human stomach, rapidly evolves and shows wide geographical divergence. The high incidence of stomach cancer in East Asia might be related to bacterial genotype. We used newly developed comparative methods to follow the evolution of East Asian H. pylori genomes using 20 complete genome sequences from Japanese, Korean, Amerind, European, and West African strains. RESULTS: A phylogenetic tree of concatenated well-defined core genes supported divergence of the East Asian lineage (hspEAsia; Japanese and Korean) from the European lineage ancestor, and then from the Amerind lineage ancestor. Phylogenetic profiling revealed a large difference in the repertoire of outer membrane proteins (including oipA, hopMN, babABC, sabAB and vacA-2) through gene loss, gain, and mutation. All known functions associated with molybdenum, a rare element essential to nearly all organisms that catalyzes two-electron-transfer oxidation-reduction reactions, appeared to be inactivated. Two pathways linking acetyl~CoA and acetate appeared intact in some Japanese strains. Phylogenetic analysis revealed greater divergence between the East Asian (hspEAsia) and the European (hpEurope) genomes in proteins in host interaction, specifically virulence factors (tipα), outer membrane proteins, and lipopolysaccharide synthesis (human Lewis antigen mimicry) enzymes. Divergence was also seen in proteins in electron transfer and translation fidelity (miaA, tilS), a DNA recombinase/exonuclease that recognizes genome identity (addA), and DNA/RNA hybrid nucleases (rnhAB). Positively selected amino acid changes between hspEAsia and hpEurope were mapped to products of cagA, vacA, homC (outer membrane protein), sotB (sugar transport), and a translation fidelity factor (miaA). Large divergence was seen in genes related to antibiotics: frxA (metronidazole resistance), def (peptide deformylase, drug target), and ftsA (actin-like, drug target). CONCLUSIONS: These results demonstrate dramatic genome evolution within a species, especially in likely host interaction genes. The East Asian strains appear to differ greatly from the European strains in electron transfer and redox reactions. These findings also suggest a model of adaptive evolution through proteome diversification and selection through modulation of translational fidelity. The results define H. pylori East Asian lineages and provide essential information for understanding their pathogenesis and designing drugs and therapies that target them.

Helicobacter suis KB1 derived from pig gastric lymphoid follicles induces the formation of gastric lymphoid follicles in mice through the activation of B cells and CD4 positive cells.

"Helicobacter heilmannii" ("H. heilmannii"), which belongs to the genus Helicobacter, is a group of bacterial species that display a long spiral-shaped morphology. Recent studies have demonstrated that "H. heilmannii" type 1 is actually H. suis, which mainly colonizes the stomachs of various animals and humans. However, the influence of H. suis on gastric diseases remains to be fully elucidated. In this report, we revealed the relationship between natural H. suis infection and follicular gastritis in the pig stomachs. From sequence analysis of the 16S rRNA, urease A, and urease B genes, the presence of H. suis was confirmed in pig gastric lymphoid follicles, and this bacterium was named H. suis KB1. In addition, H. suis KB1 was inoculated into C57BL/6J mice, and the following mouse model of the pathogenesis of follicular gastritis by H. suis infection was established: H. suis KB1 colonizes the mouse stomach, and moreover, induces the development of lymphoid follicles and acquired immune responses characterized by the activation of B cells and CD4 positive cells. These results may lead to better understanding of the relationship between H. suis and gastric diseases, especially follicular gastritis; and furthermore, our findings emphasize the zoonotic aspects of animal-human infection by H. suis.

Birth and death of genes linked to chromosomal inversion.

The birth and death of genes is central to adaptive evolution, yet the underlying genome dynamics remain elusive. The availability of closely related complete genome sequences helps to follow changes in gene contents and clarify their relationship to overall genome organization. Helicobacter pylori, bacteria in our stomach, are known for their extreme genome plasticity through mutation and recombination and will make a good target for such an analysis. In comparing their complete genome sequences, we found that gain and loss of genes (loci) for outer membrane proteins, which mediate host interaction, occurred at breakpoints of chromosomal inversions. Sequence comparison there revealed a unique mechanism of DNA duplication: DNA duplication associated with inversion. In this process, a DNA segment at one chromosomal locus is copied and inserted, in an inverted orientation, into a distant locus on the same chromosome, while the entire region between these two loci is also inverted. Recognition of this and three more inversion modes, which occur through reciprocal recombination between long or short sequence similarity or adjacent to a mobile element, allowed reconstruction of synteny evolution through inversion events in this species. These results will guide the interpretation of extensive DNA sequencing results for understanding long- and short-term genome evolution in various organisms and in cancer cells.