Many host-adapted bacterial pathogens contain DNA methyltransferases (mod genes) that are subject to phase-variable expression (high-frequency reversible ON/OFF switching of gene expression). In Haemophilus influenzae and pathogenic Neisseria, the random modA gene, associated with a type III restriction modification (R-M) system, controls regulon genes (a "phasevarion"), via differential methylation genome in ON OFF states. Phase-variable R-M systems also found Helicobacter pylori,...

Significance Bacteria can obtain genes from other bacteria, or the surrounding environment, by horizontal gene transfer (HGT). While it is clear that HGT very important for microbial populations, not understood how changes rate mechanisms of adaptation. In this study, we evolve populations bacteria Helicobacter pylori and use DNA sequencing to track movement as they spread through population. We show help antibiotic resistance establish at a low frequency in population, even absence...

Enterotoxigenic Escherichia coli (ETEC) is an enteric pathogen that causes cholera-like diarrhea in humans and animals. ETEC secretes a heat-labile enterotoxin (LT), which resembles cholera toxin, but the actual mechanism of LT secretion presently unknown. We have identified previously unrecognized type II protein pathway prototypic human strain, H10407 (serotype O78:H11). The genes for this are absent from E. K-12, although examination K-12 genome suggests it probably once possessed them....

The type IV secretion system (T4SS) of Helicobacter pylori triggers massive inflammatory responses during gastric infection by mechanisms that are poorly understood. Here we provide evidence for a novel pathway which the T4SS structural component, CagL, induces interleukin-8 (IL-8) independently CagA translocation and peptidoglycan-sensing nucleotide-binding oligomerization domain 1 (NOD1) signalling. Recombinant CagL was sufficient to trigger IL-8 secretion, requiring activation α5 β1...

Autotransporters are secreted proteins that assembled into the outer membrane of bacterial cells. The passenger domains autotransporters crucial for pathogenesis, with some remaining attached to surface while others released by proteolysis. An enigma remains as whether should be considered a class secretion system, or simply substrate peculiar requirements their secretion. We sought establish sensitive search protocol could identify and characterize diverse from genome sequence data. new...

Ethoxzolamide (EZA), acetazolamide, and methazolamide are clinically used sulphonamide drugs designed to treat non-bacteria-related illnesses (e.g. glaucoma), but they also show antimicrobial activity against the gastric pathogen Helicobacter pylori. EZA showed highest activity, was effective clinical isolates resistant metronidazole, clarithromycin, and/or amoxicillin, suggesting that kills H. pylori via mechanisms different from of these antibiotics. The frequency single-step spontaneous...

ABSTRACT Picornavirus RNA replication requires the formation of complexes (RCs) consisting virus-induced vesicles associated with viral nonstructural proteins and RNA. Brefeldin A (BFA) has been shown to strongly inhibit poliovirus but not encephalomyocarditis virus (EMCV). Here, we demonstrate that parechovirus 1 (ParV1) is partly resistant BFA, whereas echovirus 11 (EV11) inhibited. Since BFA inhibits COPI-dependent steps in endoplasmic reticulum (ER)-Golgi transport, tested a hypothesis...

Significance Horizontal gene transfer (HGT)—the of DNA between lineages—is responsible for a large proportion the genetic variation that contributes to evolution in microbial populations. While HGT can bring beneficial innovation, from other species or strains also have deleterious effects. In this study, we evolve populations bacteria Helicobacter pylori and use sequencing identify over 40,000 variants transferred by HGT. We measure cost many these find both strongly mutations are natural...

Serotype G6 and G8 rotaviruses are rarely found in man may have originated animals. Human serotype rotaviruses, isolated from hospitalised children at various locations Australia, were characterised. Deduced amino acid sequences of the major neutralising antigen, V7, showed significant identity to cognate proteins prototype human bovine viruses, respectively, strains reacted with serotype-specific monoclonal antibodies, an enzyme immunoassay. The VP4 type was determined as P[14] for all...

The Gram-negative bacterium, Helicobacter pylori, causes chronic gastritis, peptic ulcers, and gastric cancer in humans. Although the epithelium is primary site of H. pylori colonization, can gain access to deeper tissues. Concurring with this notion, has been found vicinity endothelial cells submucosa. Endothelial play crucial roles innate immune response, wound healing tumorigenesis. This study examines molecular mechanisms by which interacts triggers inflammatory responses cells. We...

Abstract The Helicobacter pylori phase variable gene modH , typified by HP1522 in strain 26695, encodes a N 6 -adenosine type III DNA methyltransferase. Our previous studies identified multiple strain-specific variants ( modH1 – modH19 ) and showed that variation of modH5 H. P12 influenced expression motility-associated genes outer membrane protein hopG . However, the ModH5 recognition motif mechanism which controls were unknown. Here, using comparative single molecule real-time sequencing,...

The natural immune response to Helicobacter pylori neither clears infection nor prevents reinfection. However, the ability of secretory antibodies influence course H. has not been determined. We compared progression in wild-type C57BL/6 mice with that lacking polymeric immunoglobulin receptor (pIgR) is essential for secretion antibody across mucosal surfaces. SS1-infected and pIgR knockout (KO) were sampled longitudinally gastrointestinal bacterial load, response, histological changes....

Previous studies suggest overrepresentation of particular polymorphisms within the Helicobacter pylori CagL hypervariable motif (CagLHM) in gastric cancer-associated isolates. However, these disease correlations were geographically variable and ambiguous. We compared correlation several hundred diverse sequences identified 33 CagLHM sequence combinations with disparate geographical distribution, revealing substantial worldwide diversity, particularly Asian countries. Notably, E59 I60...

Bacterial infections typically elicit a strong Heat Shock Response (HSR) in host cells. However, the gastric pathogen Helicobacter pylori has unique ability to repress this response, mechanism of which yet be elucidated. This study sought characterize underlying mechanisms by H. down-modulates HSP expression upon infection. Examination isogenic mutant strains defective components type IV secretion system (T4SS), identified substrate, CagA, essential for down-modulation HSPs HSPH1 (HSP105),...

Carriage of the CagA oncoprotein by human gastric cancer-associated pathogen Helicobacter pylori is significantly associated with this typically benign chronic infection advancing to a potentially fatal outcome. However it remains be elucidated why only small subset individuals infected H. CagA-positive strains develops cancer. translocates into host cells using type IV secretion apparatus that interacts integrin receptors via three-amino-acid-residue RGD motif on protein CagL. The CagL also...

Worldwide trials of rotavirus vaccines are currently in progress, but the basis cross-reactive immunity between serotypes is yet to be elucidated. The involvement outer capsid proteins, VP7 and VP4, production neutralizing antibody (N-Ab) unclear, may important for success animal rotavirus-based candidate that lack a VP4 human origin. In this study, VP7- VP4-specific N-Ab was assayed sera from children experiencing primary (27 children) and/or secondary (14 infections using human-animal...

Sixty-eight mother-infant pairs were followed for 12–17 months after birth. Rotavirus infections in children detected by EIA of weekly fecal antigen and anti-rotavirus IgA levels, IgG sera at birth, 6, or age, neutralizing antibody (NA) monthly samples maternal breast milk. Primary rotavirus infection was 26 (in 15 [58%] excretion, 12 [46%] seroconversion, 22 [85%] elevations antibodies [IgA coproconversion] consecutive specimens). "challenge" rises levels NA milk 9 (47%) 19 mothers,...

Cytotoxin-associated gene product A (CagA) is a major virulence factor secreted by Helicobacter pylori. CagA activity in the gastric epithelium associated with higher risk of cancer development. Bacterial type IV secretion system (T4SS)-mediated translocation into cytosol human epithelial cells occurs via poorly understood mechanism that requires interaction host membrane lipid phosphatidylserine (PS) and cell receptor integrin α₅β₁. Here we have characterized isolated recombinant middle...

This study was designed to evaluate three techniques most commonly used identify the VP4 (P) types of human group A fecal rotaviruses. The included PCR with nested primers and hybridization PCR-generated probes (to determine P genotypes). results obtained by these genetic were evaluated against those an enzyme immunoassay (EIA) incorporating neutralizing monoclonal antibodies (N-MAbs) reacting major serotypes (serotypes P1A, P1B, P2A). rotaviruses present in 102 specimens determined under...

Studies of active immunization against Helicobacter pylori indicate that antibodies play a minor role in immunity. There is also evidence, however, the translocation stomach may be insufficient to achieve functional antibody levels gastric lumen. We have used suckling mouse model passive immunity determine if perorally delivered can protect infection with H. pylori. Female C57BL/6 mice were immunized parenterally formalin-fixed cells three clinical isolates (3HP) or mouse-adapted strain SS1...

Abstract Helicobacter pylori is a gram‐negative bacterial pathogen that chronically inhabits the human stomach. To survive and maintain advantage, it has evolved unique host–pathogen interactions mediated by ‐specific proteins in outer membrane. These membrane ( OMP s) are anchored to cell surface via C‐terminal β‐barrel domain, which requires their assembly machinery BAM ). Here we have assessed complexity of domains employed H. pylori, characterized complex. Around 50 s were with...

Helicobacter pylori populations recovered from the human stomach display extensive recombination and quasispecies development, this suggests frequent exchange of DNA between different strains in vivo. In vitro, however, most H. restriction to uptake non-self DNA, as measured using selectable markers, regardless their competency for transformation with self DNA. We have examined effect markers on double-crossover efficiencies three reference (1061, 26695 & SS1) one clinical isolate (CHP1)...