70 research outputs found
Private Ordering, Collective Action, and the Self-Enforcing Range of Contracts. The Case of French Livestock Industry
Contract enforcement is acknowledged as a major issue in Law and in Economics. Contrasting substitution and complementary perspectives with respect to the role of private versus public enforcement institutions, this article analyses how contract law can support private institutions, and enhance economic efficiency. With multilateral agreements at stake, self-regulation and reputation mechanisms at the core of private ordering have limitations that collective organizations backed by the Law help to overcome. The analysis is substantiated by empirical data from the cattle industry. Our results suggest the need for a broader approach to contract regulation by legal scholars and antitrust-authorities.Contract Law, Private Enforcement, Transaction Costs, Self-Regulation, Coalitions, Cartels, Collective Organization
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
Positive selection in the evolution of Helicobacter pylori outer membrane proteins
Homologous recombination in Helicobacter pylori has been extensively described to
occur via Outer Membrane Proteins (OMPs), regulating protein expression and
generating allelic diversity, while the importance of single nucleotide polymorphisms
(SNP) remains little studied.
We used an OMP-encoding gene, homC, as a model to evaluate the weight of
positive selection in the evolution of H. pylori, by using G200 sequences obtained
from strains collected worldwide. N-site and branch-site phylogenetic analysis by
maximum likelihood models were used to identify specific codons that may be
important in homC evolution, and to evaluate the impact of selective pressure on
the geographic segregation of strains, respectively.
The N-site overall analysis showed that 14 of the 742 (1.9%) homC codons are
likely under positive selection (likelihood-ratio test (LRT), p < 10-61). Four of
these codons are located in the most variable allelic gene middle region, probably
reflecting recombination-derived hitchhiking events. On the other hand, eight
codons are located in the more conserved 5¢and 3¢ gene regions, although the
significance of this distribution remains to be clarified.
Branch-site analysis revealed 36 codons (4.9%) under positive selection (LRT,
p < 10-41), showing a non-random distribution, and 89% of these particular
codons (p < 10-3) support the phylogenetic segregation of European strains from
both African and East Asian strains. The lack of visible recombination within this
segment suggests an important biological role of point mutations in the evolution
of H. pylori OMPs.
In conclusion, homC SNP analysis suggests that, besides recombination, positive
selection contributes as well to the evolution of H. pylori OMPs
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
Diversity and phylogeny of the Helicobacter pylori outer membrane protein-encoding gene homC
The genetic diversity and evolution of the homC gene was evaluated 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.
All the strains tested harboured a complete homC gene at a conserved locus.
Phylogenetic reconstruction of homC showed a geographical segregation, with
three predominant groups: Western, East Asian/Amerindian and African. A
similarity plot analysis suggested a conserved profile of gene segmentation, where
three segments were defined. In the first segment (5¢ end extremity), sequences
were separated according to the geographical origin of the strain. A higher level of
diversity (<50%) was observed in the middle segment, while the third segment (3¢
end extremity) was the most conserved (~90%). In the middle segment, eight
allelic variants were identified, with geographic specificity regarding the most
prevalent ones. The AI allele was predominant and exclusive of Western strains.
The AII allele was predominant in African strains and was the only allele present
in the three geographical groups. The AIV allele was predominant in East Asian/
Amerindian strains and was not observed in Western strains. The Western group
showed greater molecular distance while the sequences from the East Asian/
Amerindian group were the closest.
Overall, the regular presence of homC and its allelic variability suggest that this
gene is a good candidate to be part of the pool of H. pylori outer membrane
proteins involved in bacterial persistence
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
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
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
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
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