The Influence of Gastric Microbiota and Probiotics in Infection and Associated Diseases.

The role of microbiota in human health and disease is becoming increasingly clear as a result of modern microbiome studies in recent decades. The gastrointestinal tract is the major habitat for microbiota in the human body. This microbiota comprises several trillion microorganisms, which is equivalent to almost ten times the total number of cells of the human host.

Cultivation and molecular characterization of viable Helicobacter pylori from the root canal of 170 deciduous teeth of children.

Background: Helicobacter pylori is a persistent pathogen in the human stomach. However, the proposed transmission route via the oral cavity is not understood and under intense debate. While dozens of studies have shown by PCR that H.

Two remarkable serine/leucine polymorphisms in Helicobacter pylori: functional importance for serine protease HtrA and adhesin BabA.

Single nucleotide polymorphisms (SNPs) account for significant genomic variability in microbes, including the highly diverse gastric pathogen Helicobacter pylori. However, data on the effects of specific SNPs in pathogen-host interactions are scarce. Recent functional studies unravelled how a serine/leucine polymorphism in serine protease HtrA affects the formation of proteolytically active trimers and modulates cleavage of host cell-to-cell junction proteins during infection.

Cancer-associated SNPs in bacteria: lessons from Helicobacter pylori.

Several single-nucleotide polymorphisms (SNPs) in human chromosomes are known to predispose to cancer. However, cancer-associated SNPs in bacterial pathogens were unknown until discovered in the stomach pathogen Helicobacter pylori. Those include an alanine-threonine polymorphism in the EPIYA-B phosphorylation motif of the injected effector protein CagA that affects cancer risk by modifying inflammatory responses and loss of host cell polarity.

Helicobacter pylori-Induced Host Cell DNA Damage and Genetics of Gastric Cancer Development.

Gastric cancer is a very serious and deadly disease worldwide with about one million new cases every year. Most gastric cancer subtypes are associated with genetic and epigenetic aberrations caused by chromosome instability, microsatellite instability or Epstein-Barr virus infection. Another risk factor is an infection with Helicobacter pylori, which also triggers severe alterations in the host genome.

Pathogenomics of Helicobacter pylori.

The human stomach bacterium Helicobacter pylori, the causative agent of gastritis, ulcers and adenocarcinoma, possesses very high genetic diversity. H. pylori has been associated with anatomically modern humans since their origins over 100,000 years ago and has co-evolved with its human host ever since.

A single-nucleotide polymorphism in Helicobacter pylori promotes gastric cancer development.

Single-nucleotide polymorphisms (SNPs) in various human genes are key factors in carcinogenesis. However, whether SNPs in bacterial pathogens are similarly crucial in cancer development is unknown. Here, we analyzed 1,043 genomes of the stomach pathogen Helicobacter pylori and pinpointed a SNP in the serine protease HtrA (position serine/leucine 171) that significantly correlates with gastric cancer.

Early and late genome-wide gastric epithelial transcriptome response during infection with the human carcinogen .

Infection of the stomach by is a major risk factor for the development of gastric cancer. Colonization of the gastric epithelium leads to the activation of multiple disease-related signaling pathways. Serine protease HtrA represents an important secreted virulence factor that mediates cleavage of cellular junctions.

Evolution and Role of Proteases in Lifestyle and Pathogenesis.

Infection with the main human food-borne pathogen causes campylobacteriosis that accounts for a substantial percentage of gastrointestinal infections. The disease usually manifests as diarrhea that lasts for up to two weeks. possesses an array of peptidases and proteases that are critical for its lifestyle and pathogenesis.

Contribution of a Novel Pertussis Toxin-Like Factor in Mediating Persistent Otitis Media.

Chronic otitis media (COM) is the long-term infection and inflammation of the middle ears typically caused by upper respiratory tract pathogens that are able to ascend the Eustachian tube. Our understanding of contributing factors is limited because human otopathogens cannot naturally colonize or persist in the middle ears of mice. We recently described a natural COM in mice caused by and proposed this as an experimental system to study bacterial mechanisms of immune evasion that allow persistent infection of the middle ear.

Modeling the catarrhal stage of Bordetella pertussis upper respiratory tract infections in mice.

Pertussis (whooping cough) is a highly transmissible human respiratory disease caused by Bordetella pertussis, a human-restricted pathogen. Animal models generally involve pneumonic infections induced by depositing large numbers of bacteria in the lungs of mice. These models have informed us about the molecular pathogenesis of pertussis and guided development of vaccines that successfully protect against severe disease.

Unique TLR9 Activation by Helicobacter pylori Depends on the cag T4SS, But Not on VirD2 Relaxases or VirD4 Coupling Proteins.

The genomes of the gastric bacterial pathogen Helicobacter pylori harbor multiple type-IV secretion systems (T4SSs). Here we analyzed components of three T4SSs, the cytotoxin-associated genes (cag) T4SS, TFS3 and TFS4. The cag T4SS delivers the effector protein CagA and the LPS-metabolite ADP-heptose into gastric epithelial cells, which plays a pivotal role in chronic infection and development of gastric disease.

Natural History and Ecology of Interactions Between Species and Amoeba.

A variety of bacteria have evolved the ability to interact with environmental phagocytic predators such as amoebae, which may have facilitated their subsequent interactions with phagocytes in animal hosts. Our recent study found that the animal pathogen can evade predation by the common soil amoeba , survive within, and hijack its complex life cycle as a propagation and dissemination vector. However, it is uncertain whether the mechanisms allowing interactions with predatory amoebae are conserved among species, because divergence, evolution, and adaptation to different hosts and ecological niches was accompanied by acquisition and loss of many genes.

Pertactin contributes to shedding and transmission of Bordetella bronchiseptica.

Whooping cough is resurging in the United States despite high vaccine coverage. The rapid rise of Bordetella pertussis isolates lacking pertactin (PRN), a key vaccine antigen, has led to concerns about vaccine-driven evolution. Previous studies showed that pertactin can mediate binding to mammalian cells in vitro and act as an immunomodulatory factor in resisting neutrophil-mediated clearance.

Modeling Immune Evasion and Vaccine Limitations by Targeted Nasopharyngeal Bordetella pertussis Inoculation in Mice.

Conventional pertussis animal models deliver hundreds of thousands of Bordetella pertussis bacteria deep into the lungs, rapidly inducing severe pneumonic pathology and a robust immune response. However, human infections usually begin with colonization and growth in the upper respiratory tract. We inoculated only the nasopharynx of mice to explore the course of infection in a more natural exposure model.

's historical journey through Siberia and the Americas.

The gastric bacterium shares a coevolutionary history with humans that predates the out-of-Africa diaspora, and the geographical specificities of populations reflect multiple well-known human migrations. We extensively sampled from 16 ethnically diverse human populations across Siberia to help resolve whether ancient northern Eurasian populations persisted at high latitudes through the last glacial maximum and the relationships between present-day Siberians and Native Americans. A total of 556 strains were cultivated and genotyped by multilocus sequence typing, and 54 representative draft genomes were sequenced.

Campylobacter Virulence Factors and Molecular Host-Pathogen Interactions.

Campylobacter jejuni and Campylobacter coli can be frequently isolated from poultry and poultry-derived products, and in combination these two species cause a large portion of human bacterial gastroenteritis cases. While birds are typically colonized by these Campylobacter species without clinical symptoms, in humans they cause (foodborne) infections at high frequencies, estimated to cost billions of dollars worldwide every year. The clinical outcome of Campylobacter infections comprises malaise, diarrhea, abdominal pain and fever.

Evolution and Conservation of Intracellular Survival in Eukaryotic Host Cells.

The classical bordetellae possess several partially characterized virulence mechanisms that are studied in the context of a complete extracellular life cycle in their mammalian hosts. Yet, classical bordetellae have repeatedly been reported within dendritic cells (DCs) and alveolar macrophages in clinical samples, and experiments convincingly demonstrate that the bacteria can survive intracellularly within mammalian phagocytic cells, an ability that appears to have descended from ancestral progenitor species that lived in the environment and acquired the mechanisms to resist unicellular phagocytic predators. Many pathogens, including , , , and , are known to parasitize and multiply inside eukaryotic host cells.

Acellular Pertussis Vaccine Components: Today and Tomorrow.

Pertussis is a highly communicable acute respiratory infection caused by Immunity is not lifelong after natural infection or vaccination. Pertussis outbreaks occur cyclically worldwide and effective vaccination strategies are needed to control disease. Whole-cell pertussis (wP) vaccines became available in the 1940s but have been replaced in many countries with acellular pertussis (aP) vaccines.

Conservation of Ancient Genetic Pathways for Intracellular Persistence Among Animal Pathogenic Bordetellae.

Animal and human pathogens of the genus are not commonly considered to be intracellular pathogens, although members of the closely related classical bordetellae are known to enter and persist within macrophages and have anecdotally been reported to be intracellular in clinical samples. , the species closest to the ancestral lineage of the classical bordetellae, infects a wide range of mammals but is known to have an alternate life cycle, persisting, replicating and disseminating with amoeba. These observations give rise to the hypothesis that the ability for intracellular survival has an ancestral origin and is common among animal-pathogenic and environmental species.

Enhancement of immune response against Bordetella spp. by disrupting immunomodulation.

Well-adapted pathogens must evade clearance by the host immune system and the study of how they do this has revealed myriad complex strategies and mechanisms. Classical bordetellae are very closely related subspecies that are known to modulate adaptive immunity in a variety of ways, permitting them to either persist for life or repeatedly infect the same host. Exploring the hypothesis that exposure to immune cells would cause bordetellae to induce expression of important immunomodulatory mechanisms, we identified a putative regulator of an immunomodulatory pathway.

in ancient human remains.

The bacterium () infects the stomachs of approximately 50% of all humans. With its universal occurrence, high infectivity and virulence properties it is considered as one of the most severe global burdens of modern humankind. It has accompanied humans for many thousands of years, and due to its high genetic variability and vertical transmission, its population genetics reflects the history of human migrations.

Genotypic and phenotypic adaptation of pathogens: lesson from the genus Bordetella.

Purpose Of Review: To relate genomic changes to phenotypic adaptation and evolution from environmental bacteria to obligate human pathogens, focusing on the examples within Bordetella species.

Recent Findings: Recent studies showed that animal-pathogenic and human-pathogenic Bordetella species evolved from environmental ancestors in soil. The animal-pathogenic Bordetella bronchiseptica can hijack the life cycle of the soil-living amoeba Dictyostelium discoideum, surviving inside single-celled trophozoites, translocating to the fruiting bodies and disseminating along with amoeba spores.

Virulent Epidemic Pneumonia in Sheep Caused by the Human Pathogen .

The human pathogen has emerged as a frequent cause of hospital-acquired infections, but infection of animals has rarely been observed. Here we analyzed an outbreak of epidemic pneumonia killing hundreds of sheep on a farm in Pakistan and identified as the infecting agent. A pure culture of strain AbPK1 isolated from lungs of sick animals was inoculated into healthy sheep, which subsequently developed similar disease symptoms.

Blood or Serum Exposure Induce Global Transcriptional Changes, Altered Antigenic Profile, and Increased Cytotoxicity by Classical Bordetellae.

The classical bordetellae sense and respond to a variety of environments outside and within their mammalian hosts. By causing inflammation and tissue damage, we reasoned that bordetellae are likely to encounter components of blood and/or serum during the course of a respiratory infection, and that detecting and responding to these would be advantageous. Therefore, we hypothesized that classical bordetellae have the ability to sense and respond to blood or serum.