Host-Interactive Genes in Amerindian Helicobacter pylori Diverge from Their Old World Homologs and Mediate Inflammatory Responses

Helicobacter pylori is the dominant member of the gastric microbiota and has been associated with an increased risk of gastric cancer and peptic ulcers in adults. H. pylori populations have migrated and diverged with human populations, and health effects vary. Here, we describe the whole genome of the cag-positive strain V225d, cultured from a Venezuelan Piaroa Amerindian subject. To gain insight into the evolution and host adaptation of this bacterium, we undertook comparative H. pylori genomic analyses. A robust multiprotein phylogenetic tree reflects the major human migration out of Africa, across Europe, through Asia, and into the New World, placing Amerindian H. pylori as a particularly close sister group to East Asian H. pylori. In contrast, phylogenetic analysis of the host-interactive genes vacA and cagA shows substantial divergence of Amerindian from Old World forms and indicates new genotypes (e.g., VacA m3) involving these loci. Despite deletions in CagA EPIYA and CRPIA domains, V225d stimulates interleukin-8 secretion and the hummingbird phenotype in AGS cells. However, following a 33-week passage in the mouse stomach, these phenotypes were lost in isolate V225-RE, which had a 15-kb deletion in the cag pathogenicity island that truncated CagA and eliminated some of the type IV secretion system genes. Thus, the unusual V225d cag architecture was fully functional via conserved elements, but the natural deletion of 13 cag pathogenicity island genes and the truncation of CagA impaired the ability to induce inflammation.Helicobacter pylori is a microaerophilic bacterium of the Epsilonproteobacteria that has colonized the stomach since early in human evolution (45) and diverged with ancient human migrations (24, 45, 92). Thus, several major H. pylori populations, such as hpAfrica1, hpEurope, hspEAsia, and hspAmerind, whose names indicate their original geographic associations (45, 51), have been defined. In particular, similarities between the hspAmerind and hspEAsia populations suggest that the first colonizers of the New World brought H. pylori with them (24, 28). With recent mixing of human groups, H. pylori populations are also mixing and competing, with an apparent dominance by the hpEurope population at least in Latin America (19).H. pylori usually does not cause illness, but colonization with strains bearing the cag (cytotoxin-associated gene) pathogenicity island (cag PAI) (3, 7, 25, 52, 57, 61, 63) is associated with an increased risk of noncardia gastric adenocarcinoma and peptic ulcer disease (56, 64). Nonetheless, a high prevalence of cag-positive H. pylori strains occurs concurrently with low gastric cancer rates in Africa (40) and some regions in Latin America, such as the Venezuelan savannas and Amazonas (29, 53). Moreover, clinical and epidemiological data provide evidence for an inverse relationship between H. pylori colonization and the prevalence of certain metabolic disorders, esophageal diseases, asthma and allergic disorders, and acute infectious diseases, as well as a direct relationship with improved nutritional status of rural children (3, 14, 34, 37, 49, 68). That the host interaction with an indigenous gastric microbe provides some health benefits to the host is not unexpected given the well-established role of gastrointestinal microflora in maintaining gastroenteric homeostasis (8).The most thoroughly studied H. pylori proteins that interact with human cells are CagA and VacA. CagA is an effector protein injected into gastric epithelial cells by a type IV secretion system encoded by the cag PAI (10, 12, 15, 83). VacA is initially secreted from the bacterial cell by an autotransporter mechanism (16). Both proteins have multiple effects on host cells. Inside the host cell, phosphorylation of CagA on EPIYA repeats in the phosphotyrosine (PY) region (73) induces cellular elongation known as the hummingbird phenotype (72). CagA may also induce secretion of interleukin-8 (IL-8) (11), a process commonly attributed to NF-κB, and disrupt the barrier function of the tight junctions in polarized epithelial cells, leading to a loss of adhesion (1, 5). Other motifs in the PY region promote phosphorylation-independent effects (79). In addition, cagA may be considered an oncogene (60), since transgenic expression of cagA in mice leads to gastric epithelial hyperplasia through aberrant epithelial cell signaling and gastric carcinogenesis (60, 62). In contrast, VacA is a multifunctional protein with several activities in epithelial and immune cells (16). VacA induces cell vacuolation (43), alters mitochondrial membrane permeability (27, 41, 90), and increases epithelial monolayer permeability. VacA also activates several signal transduction pathways that are important in immune and epithelial cells, including the mitogen-activated protein (MAP) kinase and p38/ATF-2-mediated signal pathways (9, 55).Genomic analysis provides insights into the evolution of H. pylori strains and their relation with their human hosts and may be useful for the development of diagnostic tools and novel therapies. To date, there are six published complete H. pylori genomes, mostly from the hpEurope population (see Table SA1 in the supplemental material). Here, we report the whole genome of a newly characterized hspAmerind strain, V225d, and assess its genetic structure in comparison to those of Old World H. pylori strains through a comprehensive multiprotein phylogenetic analysis, as well as through single-gene examination of cagA and vacA, revealing clues to the evolution and migration of this strain into the New World and the implications for human health. We also present the results of functional and genomic studies using gastric epithelial cells demonstrating that V225d can induce an inflammatory host response, an effect that was lost following passage through the mouse stomach.     

Genomic comparison between a virulent type A1 strain of Francisella tularensis and its attenuated O-antigen mutant

We report the complete genome sequences of TI0902, a highly virulent type A1 strain, and TIGB03, a related, attenuated chemical mutant strain. Compared to the wild type, the mutant strain had 45 point mutations and a 75.9-kb duplicated region that had not been previously observed in Francisella species.     

African Wild Dog Dispersal and Implications for Management

Successful conservation of species that roam and disperse over large areas requires detailed understanding of their movement patterns and connectivity between subpopulations. But empirical information on movement, space use, and connectivity is lacking for many species, and data acquisition is often hindered when study animals cross international borders. The African wild dog (Lycaon pictus) exemplifies such species that require vast undisturbed areas to support viable, self-sustaining populations. To study wild dog dispersal and investigate potential barriers to movements and causes of mortality during dispersal, between 2016 and 2019 we followed the fate of 16 dispersing coalitions (i.e., same-sex group of ≥1 dispersing African wild dogs) in northern Botswana through global positioning system (GPS)-satellite telemetry. Dispersing wild dogs covered ≤54 km in 24 hours and traveled 150 km to Namibia and 360 km to Zimbabwe within 10 days. Wild dogs were little hindered in their movements by natural landscape features, whereas medium to densely human-populated landscapes represented obstacles to dispersal. Human-caused mortality was responsible for >90% of the recorded deaths. Our results suggest that a holistic approach to the management and conservation of highly mobile species is necessary to develop effective research and evidence-based conservation programs across transfrontier protected areas, including the need for coordinated research efforts through collaboration between national and international conservation authorities. © 2020 The Wildlife Society.     

Reproductive effort and phenology of seed production of savanna grasses with different growth form and life history

The phenology of seed production in natural savanna grasslands was studied in the grass speciesAristida congesta, Cymbopogon plurinodis, Cynodon dactylon, Digitaria eriantha ssp.pentzii, Eragrostis rigidior, Eragrostis superba, Panicum coloratum, Schmidtia pappophoroides, Tragus berteronianus andUrochloa panicoides. Maximum seed production varied according to life history strategy and growth form from 0.03 mg seed g^-1 shoot dry weight in the perennialD. eriantha ssp.pentzii which produces long stolons and 14.8 mg seed g^-1 shoot inE rigidior, which produces short geniculate stolons, to 169.1 mg g^-1 in the annualT. berteronianus. Seed production was in most species divided over several peaks during the season. Peaks of seed production were observed 3 to 7 months after the onset of the growth season depending on the start of the rains and the life history strategy and growth form of the species. Seed production varied from maxima of 180 seeds m^-2 inD. eriantha ssp.pentzii to 47000 seeds m^-2 in annual stands ofT. berteronianus. Except for annual grasslands withU. panicoides, seedling emergence data reported are smaller by at least a factor of 10 than the observed seed production. Among other factors, a low quality of produced seeds, predation by birds and insects and previous grazing by livestock may have contributed to this difference.