The role of Helicobacter pylori outer membrane proteins in adherence and pathogenesis

Helicobacter pylori is one of the most successful human pathogens, whichcolonizes the mucus layer of the gastric epithelium of more than 50% of the world’spopulation. This curved, microaerophilic, Gram-negative bacterium induces a chronicactive gastritis, often asymptomatic, in all infected individuals. In some cases, this gastritisevolves to more severe diseases such as peptic ulcer disease, gastric adenocarcinoma, andgastric mucosa-associated lymphoid tissue lymphoma. H. pylori has developed a unique setof factors, actively supporting its successful survival and persistence in its natural hostileecological niche, the human stomach, throughout the individual’s life, unless treated. In thehuman stomach, the vast majority of H. pylori cells are motile in the mucus layer lining,but a small percentage adheres to the epithelial cell surfaces. Adherence to the gastricepithelium is important for the ability of H. pylori to cause disease because this intimateattachment facilitates: (1) colonization and persistence, by preventing the bacteria frombeing eliminated from the stomach, by mucus turnover and gastric peristalsis; (2) evasionfrom the human immune system and (3) efficient delivery of proteins into the gastric cell,such as the CagA oncoprotein. Therefore, bacteria with better adherence propertiescolonize the host at higher densities. H. pylori is one of the most genetically diversebacterial species known and is equipped with an extraordinarily large set of outermembrane proteins, whose role in the infection and persistence process will be discussed in this review, as well as the different receptor structures that have been so far described for mucosal adherence

High worldwide conservation of a Helicobacter pylori outer membrane protein

The genetic diversity and evolution of homD, coding for Helicobacter pylori outer membrane protein (OMP) was investigated in a panel of approximately 200 clinical and reference strains, isolated from patients from different geographical origins and presenting different gastric diseases. PCR, sequencing and bioinformatics analyses were used. The homD gene was present in all strains, at a conserved locus, and showed a low genomic diversity, displaying high similarity at both nucleotide and amino acid level. A similarity plot analysis also showed a high level of sequence conservation, although a small region (~30 nucleotides) differed between Western strains and the other strains (East Asian/Ameridian and African). This region was also found in some allelic variants of another hom family member, the homC gene, suggesting the existence of recombination events between these two OMP encoding genes. Sequence analysis of the HomD predicted protein showed a N terminus region with a variable number of KP motif repeats (2 9 KP), with a correlation between the lowest number of KP motif repeats (£4 KP) and peptic ulcer disease and the highest number of repeats (£7 KP) and gastritis. In silico analysis of the HomD protein showed that the region of KP motif repeats exhibits a strong hydrophilicity and antigenicity and a high probability of being exposed to the bacterial surface, suggesting that HomD is immunogenic. These results suggest that homD gene is an important H. pylori antigen and, because of its high global conservation, it is likely to constitute a new vaccine target

Hafnia, an enterobacterial genus naturally resistant to colistin revealed by three susceptibility testing methods

ObjectivesTo determine the susceptibility to colistin of Hafnia alvei and Hafnia paralvei, and to compare methods for colistin resistance detection in the Hafnia genus.MethodsA collection of 25 Hafnia isolates was studied. Species were identified by using 16S rRNA gene sequencing with subsequent phylogeny analysis. Susceptibility to colistin was determined using the broth microdilution (BMD) reference method, the Phoenix automated system, the Rapid Polymyxin NP test, the Etest system and the disc diffusion method.ResultsThe collection consisted of 15 H. alvei and 10 H. paralvei isolates. Based on the 16S rRNA analysis, a close relationship of the Hafnia genus with naturally colistin-resistant enterobacterial genera (Proteus, Morganella, Providencia and Serratia) was identified. Susceptibility testing performed using the BMD method, the Phoenix automated system and the Rapid Polymyxin NP test revealed a high rate of colistin resistance (96%). Underestimation of colistin resistance using Etest strips (72%) and the disc diffusion method (0%) was observed.ConclusionsThe high rate of colistin resistance observed within the Hafnia genus and its close phylogenetic relationship with naturally colistin-resistant genera suggest that Hafnia is a naturally colistin-resistant enterobacterial genus

Disease association with two Helicobacter pylori duplicate outer membrane protein genes, homB and homA

<p>Abstract</p> <p>Background</p> <p><it>homB </it>encodes a <it>Helicobacter pylori </it>outer membrane protein. This gene was previously associated with peptic ulcer disease (PUD) and was shown to induce activation of interleukin-8 secretion <it>in vitro</it>, as well as contributing to bacterial adherence. Its 90%-similar gene, <it>homA</it>, was previously correlated with gastritis. The present study aimed to evaluate the gastric disease association with <it>homB </it>and <it>homA</it>, as well as with the <it>H. pylori </it>virulence factors <it>cagA</it>, <it>babA </it>and <it>vacA</it>, in 415 <it>H. pylori </it>strains isolated from patients from East Asian and Western countries. The correlation among these genotypes was also evaluated.</p> <p>Results</p> <p>Both <it>homB </it>and <it>homA </it>genes were heterogeneously distributed worldwide, with a marked difference between East Asian and Western strains. In Western strains (n = 234, 124 PUD and 110 non-ulcer dyspepsia (NUD), <it>homB</it>, <it>cagA </it>and <it>vacA </it>s1 were all significantly associated with PUD (p = 0.025, p = 0.014, p = 0.039, respectively), and <it>homA </it>was closely correlated with NUD (p = 0.072). In East Asian strains (n = 138, 73 PUD and 65 NUD), <it>homB </it>was found more frequently than <it>homA</it>, and none of these genes was associated with the clinical outcome.</p> <p>Overall, <it>homB </it>was associated with the presence of <it>cagA </it>(p = 0.043) and <it>vacA </it>s1 (p < 0.001), whereas <it>homA </it>was found more frequently in <it>cagA</it>-negative (p = 0.062) and <it>vacA </it>s2 (p < 0.001) strains.</p> <p>Polymorphisms in <it>homB </it>and <it>homA </it>copy number were observed, with a clear geographical specificity, suggesting an involvement of these genes in host adaptation. A correlation between the <it>homB </it>two-copy genotype and PUD was also observed, emphasizing the role of <it>homB </it>in the virulence of the strain.</p> <p>Conclusion</p> <p>The global results suggest that <it>homB </it>and <it>homA </it>contribute to the determination of clinical outcome.</p

Tsukamurella tyrosinosolvens - An unusual case report of bacteremic pneumonia after lung transplantation

<p>Abstract</p> <p>Background</p> <p>Lung transplant recipients have an increased risk for actinomycetales infection secondary to immunosuppressive regimen.</p> <p>Case presentation</p> <p>A case of pulmonary infection with bacteremia due to <it>Tsukamurella tyrosinosolvens </it>in a 54-year old man who underwent a double lung transplantation four years previously is presented.</p> <p>Conclusion</p> <p>The identification by conventional biochemical assays was unsuccessful and <it>hsp </it>gene sequencing was used to identify <it>Tsukamurella tyrosinosolvens</it>.</p

Allelic diversity and phylogeny of homB, a novel co-virulence marker of Helicobacter pylori

<p>Abstract</p> <p>Background</p> <p>The <it>homB </it>gene is a <it>Helicobacter pylori </it>disease-marker candidate, strongly associated with peptic ulcer disease, while <it>homA</it>, its paralogue gene with 90% sequence identity, is correlated with non-ulcer dyspepsia. The HomB encoded outer membrane protein was shown to contribute to the proinflammatory properties of <it>H. pylori </it>and also to be involved in bacterial adherence.</p> <p>This study investigated the distribution of <it>homB </it>and <it>homA </it>genes in 455 <it>H. pylori </it>strains from East Asian and Western countries, and carried out sequence comparison and phylogenetic analyses.</p> <p>Results</p> <p>Both <it>homB </it>and <it>homA </it>genes were heterogeneously distributed worldwide, with a marked difference between East Asian and Western strains.</p> <p>Analysis of <it>homB </it>and <it>homA </it>sequences revealed diversity regarding the number of copies and their genomic localization, with East Asian and Western strains presenting different genotypes. Moreover, <it>homB </it>and <it>homA </it>sequence analysis suggests regulation by phase variation. It also indicates possible recombination events, leading to gene duplication or <it>homB</it>/<it>homA </it>conversion which may as well be implicated in the regulation of these genes. Phylogenetic reconstruction of <it>homB </it>and <it>homA </it>revealed clustering according to the geographic origin of strains. Allelic diversity in the middle region of the genes was observed for both <it>homB </it>and <it>homA</it>, although there was no correlation between any allele and disease. For each gene, a dominant worldwide allele was detected, suggesting that <it>hom</it>B/<it>hom</it>A allelic variants were independent of the geographical origin of the strain. Moreover, all alleles were demonstrated to be expressed <it>in vivo</it>.</p> <p>Conclusion</p> <p>Overall, these results suggest that <it>homB </it>and <it>homA </it>genes are good candidates to be part of the pool of <it>H. pylori </it>OMPs implicated in host-bacteria interface and also contributing to the generation of antigenic variability, and thus involved in <it>H. pylori </it>persistence.</p

Autophagy induced by Helicobacter pylori infection is necessary for gastric cancer stem cell emergence

Background: The main cause of gastric cancer is the infection by the bacterium Helicobacter pylori which induces a chronic inflammation and an epithelial-to-mesenchymal transition (EMT) leading to the emergence of cells with cancer stem cell (CSC) properties. However, the underlying mechanisms have not been fully characterized. Moreover, H. pylori modulates the host cell autophagic process, but a few studies have investigated the role of this process in tumoral transformation. The aim of this study was to determine whether H. pylori-induced autophagy has a role in CSC emergence. Methods: Autophagic flux in response to H. pylori infection was characterized in AGS cell line expressing the tandem-tagged mCherry-GFP-LC3 protein and using a ratiometric flow cytometry analysis. Then, AGS and MKN45 cell lines were treated with bafilomycin or chloroquine, two pharmaceutical well-known inhibitors of autophagy, and different EMT and CSC characteristics were analyzed. Results: First, a co-expression of the gastric CSC marker CD44 and the autophagic marker LC3 in mice and human stomach tissues infected with H. pylori was observed. Then, we demonstrated in vitro that H. pylori was able to activate the autophagy process with a reduced autophagic flux. Finally, infected cells were treated with autophagy inhibitors, which reduced (i) appearance of mesenchymal phenotypes and migration ability related to EMT and (ii) CD44 expression as well as tumorsphere formation capacities reflecting CSC properties. Conclusion: In conclusion, all these data show that H. pylori-induced autophagy is implicated in gastric CSC emergence and could represent an interesting therapeutic target.This work was supported by the French foundation Ligue contre le Cancer (Pyrénées Atlantiques)

Arcobacter butzleri: Underestimated Enteropathogen

Molecular methods applied to 2,855 strains of Campylobacter-like organisms received from a surveillance network of Campylobacter infections in France identified 29 Arcobacter butzleri infections. This species ranks fourth for Campylobacteraceae isolation and appears to have the same pathogenic potential as the other species in the genus