Recent acquisition of Helicobacter pylori by Baka Pygmies

Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations and phylogenetic inference, we show that Baka almost certainly acquired their extant H. pylori through secondary contact with their agriculturalist neighbors

What traits are carried on mobile genetic elements, and why?

Although similar to any other organism, prokaryotes can transfer genes vertically from mother cell to daughter cell, they can also exchange certain genes horizontally. Genes can move within and between genomes at fast rates because of mobile genetic elements (MGEs). Although mobile elements are fundamentally self-interested entities, and thus replicate for their own gain, they frequently carry genes beneficial for their hosts and/or the neighbours of their hosts. Many genes that are carried by mobile elements code for traits that are expressed outside of the cell. Such traits are involved in bacterial sociality, such as the production of public goods, which benefit a cell's neighbours, or the production of bacteriocins, which harm a cell's neighbours. In this study we review the patterns that are emerging in the types of genes carried by mobile elements, and discuss the evolutionary and ecological conditions under which mobile elements evolve to carry their peculiar mix of parasitic, beneficial and cooperative genes

The Cytotoxic Necrotizing Factor of Yersinia pseudotuberculosis (CNFy) is Carried on Extracellular Membrane Vesicles to Host Cells

In this study we show Yersinia pseudotuberculosis secretes membrane vesicles (MVs) that contain different proteins and virulence factors depending on the strain. Although MVs from Y. pseudotuberculosis YPIII and ATCC 29833 had many proteins in common (68.8% of all the proteins identified), those located in the outer membrane fraction differed significantly. For instance, the MVs from Y. pseudotuberculosis YPIII harbored numerous Yersinia outer proteins (Yops) while they were absent in the ATCC 29833 MVs. Another virulence factor found solely in the YPIII MVs was the cytotoxic necrotizing factor (CNFy), a toxin that leads to multinucleation of host cells. The ability of YPIII MVs to transport this toxin and its activity to host cells was verified using HeLa cells, which responded in a dose-dependent manner; nearly 70% of the culture was multinucleated after addition of 5 mu g/ml of the purified YPIII MVs. In contrast, less than 10% were multinucleated when the ATCC 29833 MVs were added. Semi-quantification of CNFy within the YPIII MVs found this toxin is present at concentrations of 5 -10 ng per mu g of total MV protein, a concentration that accounts for the cellular responses see

Molecular Characterization of Transcriptional Regulation of rovA by PhoP and RovA in Yersinia pestis

BACKGROUND: Yersinia pestis is the causative agent of plague. The two transcriptional regulators, PhoP and RovA, are required for the virulence of Y. pestis through the regulation of various virulence-associated loci. They are the global regulators controlling two distinct large complexes of cellular pathways. METHODOLOGY/PRINCIPAL FINDINGS: Based on the LacZ fusion, primer extension, gel mobility shift, and DNase I footprinting assays, RovA is shown to recognize both of the two promoters of its gene in Y. pestis. The autoregulation of RovA appears to be a conserved mechanism shared by Y. pestis and its closely related progenitor, Y. pseudotuberculosis. In Y. pestis, the PhoP regulator responds to low magnesium signals and then negatively controls only one of the two promoters of rovA through PhoP-promoter DNA association. CONCLUSIONS/SIGNIFICANCE: RovA is a direct transcriptional activator for its own gene in Y. pestis, while PhoP recognizes the promoter region of rovA to repress its transcription. The direct regulatory association between PhoP and RovA bridges the PhoP and RovA regulons in Y. pestis

Linking species concepts to natural product discovery in the post-genomic era

A widely accepted species concept for bacteria has yet to be established. As a result, species designations are inconsistently applied and tied to what can be considered arbitrary metrics. Increasing access to DNA sequence data and clear evidence that bacterial genomes are dynamic entities that include large numbers of horizontally acquired genes have added a new level of insight to the ongoing species concept debate. Despite uncertainties over how to apply species concepts to bacteria, there is clear evidence that sequence-based approaches can be used to resolve cohesive groups that maintain the properties of species. This cohesion is clearly evidenced in the genus Salinispora, where three species have been discerned despite very close relationships based on 16S rRNA sequence analysis. The major phenotypic differences among the three species are associated with secondary metabolite production, which occurs in species-specific patterns. These patterns are maintained on a global basis and provide evidence that secondary metabolites have important ecological functions. These patterns also suggest that an effective strategy for natural product discovery is to target the cultivation of new Salinispora taxa. Alternatively, bioinformatic analyses of biosynthetic genes provide opportunities to predict secondary metabolite novelty and reduce the redundant isolation of well-known metabolites. Although much remains to be learned about the evolutionary relationships among bacteria and how fundamental units of diversity can be resolved, genus and species descriptions remain the most effective method of scientific communication

Whole genome sequencing to investigate the emergence of clonal complex 23 Neisseria meningitidis serogroup Y disease in the United States

In the United States, serogroup Y, ST-23 clonal complex Neisseria meningitidis was responsible for an increase in meningococcal disease incidence during the 1990s. This increase was accompanied by antigenic shift of three outer membrane proteins, with a decrease in the population that predominated in the early 1990s as a different population emerged later in that decade. To understand factors that may have been responsible for the emergence of serogroup Y disease, we used whole genome pyrosequencing to investigate genetic differences between isolates from early and late N. meningitidis populations, obtained from meningococcal disease cases in Maryland in the 1990s. The genomes of isolates from the early and late populations were highly similar, with 1231 of 1776 shared genes exhibiting 100% amino acid identity and an average πN = 0.0033 and average πS = 0.0216. However, differences were found in predicted proteins that affect pilin structure and antigen profile and in predicted proteins involved in iron acquisition and uptake. The observed changes are consistent with acquisition of new alleles through horizontal gene transfer. Changes in antigen profile due to the genetic differences found in this study likely allowed the late population to emerge due to escape from population immunity. These findings may predict which antigenic factors are important in the cyclic epidemiology of meningococcal disease

Dynamics of Genome Rearrangement in Bacterial Populations

Genome structure variation has profound impacts on phenotype in organisms ranging from microbes to humans, yet little is known about how natural selection acts on genome arrangement. Pathogenic bacteria such as Yersinia pestis, which causes bubonic and pneumonic plague, often exhibit a high degree of genomic rearrangement. The recent availability of several Yersinia genomes offers an unprecedented opportunity to study the evolution of genome structure and arrangement. We introduce a set of statistical methods to study patterns of rearrangement in circular chromosomes and apply them to the Yersinia. We constructed a multiple alignment of eight Yersinia genomes using Mauve software to identify 78 conserved segments that are internally free from genome rearrangement. Based on the alignment, we applied Bayesian statistical methods to infer the phylogenetic inversion history of Yersinia. The sampling of genome arrangement reconstructions contains seven parsimonious tree topologies, each having different histories of 79 inversions. Topologies with a greater number of inversions also exist, but were sampled less frequently. The inversion phylogenies agree with results suggested by SNP patterns. We then analyzed reconstructed inversion histories to identify patterns of rearrangement. We confirm an over-representation of “symmetric inversions”—inversions with endpoints that are equally distant from the origin of chromosomal replication. Ancestral genome arrangements demonstrate moderate preference for replichore balance in Yersinia. We found that all inversions are shorter than expected under a neutral model, whereas inversions acting within a single replichore are much shorter than expected. We also found evidence for a canonical configuration of the origin and terminus of replication. Finally, breakpoint reuse analysis reveals that inversions with endpoints proximal to the origin of DNA replication are nearly three times more frequent. Our findings represent the first characterization of genome arrangement evolution in a bacterial population evolving outside laboratory conditions. Insight into the process of genomic rearrangement may further the understanding of pathogen population dynamics and selection on the architecture of circular bacterial chromosomes

Genetic variation and linkage disequilibrium in Bacillus anthracis

We performed whole-genome amplification followed by hybridization of custom-designed resequencing arrays to resequence 303 kb of genomic sequence from a worldwide panel of 39 Bacillus anthracis strains. We used an efficient algorithm contained within a custom software program, UniqueMER, to identify and mask repetitive sequences on the resequencing array to reduce false-positive identification of genetic variation, which can arise from cross-hybridization. We discovered a total of 240 single nucleotide variants (SNVs) and showed that B. anthracis strains have an average of 2.25 differences per 10,000 bases in the region we resequenced. Common SNVs in this region are found to be in complete linkage disequilibrium. These patterns of variation suggest there has been little if any historical recombination among B. anthracis strains since the origin of the pathogen. This pattern of common genetic variation suggests a framework for recognizing new or genetically engineered strains

Yersinia enterocolitica palearctica serobiotype O:3/4 - a successful group of emerging zoonotic pathogens

<p>Abstract</p> <p>Background</p> <p>High-pathogenic <it>Y. enterocolitica </it>ssp. <it>enterocolitica </it>caused several human outbreaks in Northern America. In contrast, low pathogenic <it>Y. enterocolitica </it>ssp. <it>palearctica </it>serobiotype O:3/4 is responsible for sporadic cases worldwide with asymptomatic pigs being the main source of infection. Genomes of three <it>Y. enterocolitica </it>ssp. <it>palearctica </it>serobiotype O:3/4 human isolates (including the completely sequenced Y11 German DSMZ type strain) were compared to the high-pathogenic <it>Y. enterocolitica </it>ssp. <it>enterocolitica </it>8081 O:8/1B to address the peculiarities of the O:3/4 group.</p> <p>Results</p> <p>Most high-pathogenicity-associated determinants of <it>Y. enterocolitica </it>ssp. <it>enterocolitica </it>(like the High-Pathogenicity Island, <it>yts1 </it>type 2 and <it>ysa </it>type 3 secretion systems) are absent in <it>Y. enterocolitica </it>ssp. <it>palearctica </it>serobiotype O:3/4 genomes. On the other hand they possess alternative putative virulence and fitness factors, such as a different <it>ysp </it>type 3 secretion system, an RtxA-like and insecticidal toxins, and a N-acetyl-galactosamine (GalNAc) PTS system (<it>aga</it>-operon). Horizontal acquisition of two prophages and a tRNA-Asn-associated GIYep-01 genomic island might also influence the <it>Y. enterocolitica </it>ssp. <it>palearctica </it>serobiotype O:3/4 pathoadaptation. We demonstrated recombination activity of the PhiYep-3 prophage and the GIYep-01 island and the ability of the <it>aga</it>-operon to support the growth of the <it>Y. enterocolitica </it>ssp. <it>enterocolitica </it>O:8/1B on GalNAc.</p> <p>Conclusions</p> <p><it>Y. enterocolitica </it>ssp. <it>palearctica </it>serobiotype O:3/4 experienced a shift to an alternative patchwork of virulence and fitness determinants that might play a significant role in its host pathoadaptation and successful worldwide dissemination.</p

Oligomeric Coiled-Coil Adhesin YadA Is a Double-Edged Sword

Yersinia adhesin A (YadA) is an essential virulence factor for the food-borne pathogens Yersinia enterocolitica and Yersinia pseudotuberculosis. Suprisingly, it is a pseudogene in Yersinia pestis. Even more intriguing, the introduction of a functional yadA gene in Y. pestis EV76 was shown to correlate with a decrease in virulence in a mouse model. Here, we report that wild type (wt) Y. enterocolitica E40, as well as YadA-deprived E40 induced the synthesis of neutrophil extracellular traps (NETs) upon contact with neutrophils, but only YadA-expressing Y. enterocolitica adhered to NETs and were killed. As binding seemed to be a prerequisite for killing, we searched for YadA-binding substrates and detected the presence of collagen within NETs. E40 bacteria expressing V98D,N99A mutant YadA with a severely reduced ability to bind collagen were found to be more resistant to killing, suggesting that collagen binding contributes significantly to sensitivity to NETs. Wt Y. pestis EV76 were resistant to killing by NETs, while recombinant EV76 expressing YadA from either Y. pseudotuberculosis or Y. enterocolitica were sensitive to killing by NETs, outlining the importance of YadA for susceptibility to NET-dependent killing. Recombinant EV76 endowed with YadA from Y. enterocolitica were also less virulent for the mouse than wt EV76, as shown before. In addition, EV76 carrying wt YadA were less virulent for the mouse than EV76 expressing YadAV98D,N99A. The observation that YadA makes Yersinia sensitive to NETs provides an explanation as for why evolution selected for the inactivation of yadA in the flea-borne Y. pestis and clarifies an old enigma. Since YadA imposes the same cost to the food-borne Yersinia but was nevertheless conserved by evolution, this observation also illustrates the duality of some virulence functions