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The Gram-negative bacterium

Helicobacter pylori is a common component of the human stomach microbiota, possibly dating back to the speciation of Homo sapiens. A history of pathogen evolution in allopatry has led to the development of genetically distinct H. pylori subpopulations, associated with different human populations, and more recent admixture among H. pylori subpopulations can provide information about human migrations. However, little is known about the degree to which some H. pylori genes are conserved in the face of admixture, potentially indicating host adaptation, or how virulence genes spread among different populations. We analyzed H. pylori genomes from 14 countries in the Americas, strains from the Iberian Peninsula, and public genomes from Europe, Africa, and Asia, to investigate how admixture varies across different regions and gene families. Whole-genome analyses of 723 H. pylori strains from around the world showed evidence of frequent admixture in the American strains with a complex mosaic of contributions from H. pylori populations originating in the Americas as well as other continents. Despite the complex admixture, distinctive genomic fingerprints were identified for each region, revealing novel American H. pylori subpopulations. A pan-genome Fst analysis showed that variation in virulence genes had the strongest fixation in America, compared with non-American populations, and that much of the variation constituted non-synonymous substitutions in functional domains. Network analyses suggest that these virulence genes have followed unique evolutionary paths in the American populations, spreading into different genetic backgrounds, potentially contributing to the high risk of gastric cancer in the region., This work was supported by “Consejo Nacional de Ciencia y Tecnología” (CONACYT; no. 576951) grant to ZYM-R, and by Magnus Bergvalls Foundation and Swedish Society for Medical Research (SSMF) to KT. SKS and BP are funded by the Medical Research Council (MR/L015080/1). Supported in part by the US National Cancer Institute National Cancer Institute to DRM (P01 CA028842, R01 CA190612, K07 CA125588, P30 CA068485). We are very grateful to Daniel Falush (Unit of Statistical Genetics of Bacteria, Institut Pasteur of Shanghai) for his critical input during the analysis of the presented data. We acknowledge the Aklavik H. pylori Project Planning Committee (Northwest Territories, Canada) for providing input on our presentation of this analysis.

Erratum in: Nat Commun. 2023 Mar 20;14(1):1539. doi: 10.1038/s41467-023-37302-5. Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori fromEurope and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying selection to remove them during admixture. Simulations show that population fitness can be restored after bottlenecks bymigration and subsequent admixture of small numbers of bacteria from non-bottlenecked populations. We conclude that recent spread of African DNA has been driven by deleterious mutations accumulated during the original out-of-Africa bottleneck. This work was supported by Sequencing Grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (221S0002, 18KK0266, 19H03473, 21H00346 and 22H02871) to Y.Y. F.F.V. is financed by FCT through Assistant Researcher grant CEECIND/03023/2017 and a project grant PTDC/BTM-TEC/3238/ 2020. I.K. studentship was funded by the National Strategic Reference Framework Operational Program “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014-2020, project No. MIS5002486) and sequencing of strains was supported by the InfeNeutra Project (NSRF 2007-2013, project no. MIS450598) of the Ministry of Culture and Edu- cation, Greece. K.T. and the sequencing of KI isolates was supported by Erik Philip-Sörensen Foundation grant G2016-08, and Swedish Society for Medical research (SSMF). All primary bioinformatics and parts of the comparative genomics were performed on resources provided by Swedish National Infrastructure for Computing (SNIC) through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under projects snic2018-8-24 and uppstore2017270. Work by S.S. was supported by the German Research Foundation (DFG, project number 158 989 968–SFB 900/A1) and by the Bavarian Ministry of Sci- ence and the Arts in the framework of the Bavarian Research Network “New Strategies Against Multi-Resistant Pathogens by Means of Digital Networking—bayresq.net”. D.F. was supported by Shanghai Municipal Science and Technology Major Project No. 2019SHZDZX02. info:eu-repo/semantics/publishedVersion

Glutaredoxin, Grx, is a small protein containing an active site cysteine pair and was discovered in 1976 by Arne Holmgren. The Grx system, comprised of Grx, glutathione, glutathione reductase, and NADPH, was first described as an electron donor for Ribonucleotide Reductase but, from the first discovery in E.coli, the Grx family has impressively grown, particularly in the last two decades. Several isoforms have been described in different organisms (from bacteria to humans) and with different functions. The unique characteristic of Grxs is their ability to catalyse glutathione-dependent redox regulation via glutathionylation, the conjugation of glutathione to a substrate, and its reverse reaction, deglutathionylation. Grxs have also recently been enrolled in iron sulphur cluster formation. These functions have been implied in various physiological and pathological conditions, from immune defense to neurodegeneration and cancer development thus making Grx a possible drug target. This review aims to give an overview on Grxs, starting by a phylogenetic analysis of vertebrate Grxs, followed by an analysis of the mechanisms of action, the specific characteristics of the different human isoforms and a discussion on aspects related to human physiology and diseases., LC, FTO and VB would like to dedicate this work to the memory of Professor Arne Holmgren, discoverer of glutaredoxin, a reference in redox research, a great mentor and storyteller. It was a privilege to work and learn from him. The authors want to thank also all the excellent scientists with whom Arne worked for their contribution to increases the knowledge about glutaredoxins. The authors thank Dr Colin Miller for proofreading the manuscript. LC was supported by the Swedish Cancer Society (961), the Swedish Research Council Medicine (13X-3529) and a grant from the Swedish Fulbright Commission (2020). VB and FFV are supported by iMed.ULisboa’s strategic project (UIDP/04138/2020; UIDB/04138/2020), financed by national funds from Fundação para a Ciência e Tecnologia, Portugal (FCT; www.fct.pt). VB is financed by national funds via Fundação para a Ciência e Tecnologia through Norma Transitória - DL57/2016/CP1376/CT002. FFV is financed by Fundação para a Ciência e Tecnologia through Assistant Researcher grant CEECIND/03023/2017.

Background Helicobacter pylori is a human gastric carcinogen that is highly prevalent in Latin American. The prophages of H. pylori show a structured population and contribute to the diversity of this bacterium. However, H. pylori prophages present in American strains have not been described to date. In this study, we identified, characterized, and present the phylogenetic analysis of the prophages present in Colombian H. pylori strains. Methods To characterize Colombian H. pylori strains and their prophages, a Multilocus Sequences Typing (MLST) and a Prophage Sequences Typing (PST), using the integrase and holin genes, were performed. Furthermore, five Colombian H. pylori had their full genome sequenced, and six Colombian H.pylori retrieved from databases, allowing to determine the prophage complete genome and insertion site. Results The integrase gene frequency was 12.6% (27/213), while both integrase and holin genes were present in 4.2% (9/213) of the samples analyzed. The PST analysis showed that Colombian prophages belong to different populations, including hpSWEurope, hpNEurope, hpAfrica1, and a new population, named hpColombia. The MLST analysis classified most of the Colombia strains in the hpEurope population. Conclusions The new H. pylori prophage population revealed that Colombian prophages follow a unique evolutionary trajectory, contributing to bacterial diversity. The global H. pylori prophage phylogeny highlighted five phylogenetic groups, one more than previously reported. After the arrival of Europeans, the Colombian H. pylori bacteria and their prophages formed an independent evolutionary line to adapt to the new environment and new human hosts.

The study of the gastric pathogen Helicobacter pylori brought us interesting data on the history of mankind. Based on multi-locus sequence typing, it was possible to trace the migration of Homo sapiens all around the world, and to infer the time when he went Out of Africa. Beside these phylogeographic aspects, paleomicrobiology gave us important information on life in the Neolithic period, following the discovery of Ötzi, the Iceman, who was living in the Tyrolean Alps 5200 years ago, and from whom a Helicobacter pylori genome was sequenced. This review presents the data accumulated in these different fields.

Background Individuals with arterial hypertension often have an autonomic nervous system (ANS) imbalance with predominance of sympathetic ANS. This predominance can lead to injury of several organs affecting its functioning. There is evidence that performing high intensity resistance training (RT) with heavier loads and a lower number of repetitions results in lower cardiovascular stress when compared with lighter loads and a higher number of repetitions. However, the effects of different protocols of RT in autonomic modulation are not known. Therefore, the aim of the study was to analyze and compare the effects of different protocols of high intensity of effort RT on autonomic cardiac modulation of hypertensive women. Methods A randomized crossover design clinical trial was conducted with 15 postmenopausal hypertensive women who underwent a control session and two high intensity RT protocols involving 6 and 15 repetition maximum (RM). Heart rate variability (HRV), systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and double product (DP) were collected pre, immediately post, 1 h post, and 24 h post each protocol. Repeated-measures ANOVA were used. Results SBP was higher for 6RM than control immediately after session (p

The review uses the Helicobacter pylori, the gastric bacterium that colonizes the human stomach, to address how to obtain information from bacterial genomes about prophage biology. In a time of continuous growing number of genomes available, this review provides tools to explore genomes for prophage presence, or other mobile genetic elements and virulence factors. The review starts by covering the genetic diversity of H. pylori and then moves to the biologic basis and the bioinformatics approaches used for studding the H. pylori phage biology from their genomes and how this is related with the bacterial population structure. Aspects concerning H. pylori prophage biology, evolution and phylogeography are discussed.

Background Helicobacter pylori infection is common in Algeria, but there are few data on the characterization of isolated strains. The aim of this study was to update data on the prevalence of H. pylori in patients submitted to endoscopy, antibiotic resistance, and phylogeography of H. pylori strains isolated in Algiers. Materials and Methods This is a prospective study carried out between November 2015 and August 2016. The culture of H. pylori was performed on antral and fundic gastric biopsies of adult patients from 3 hospitals. A real-time PCR using the fluorescence resonance energy transfer (FRET) principle for the detection of H. pylori followed by a melting curve analysis for the detection of mutations associated with resistance to clarithromycin was applied. Differentiation between antral and fundic isolates of the same patient was also determined by RAPD, and an MLST typing was performed for characterization of the phylogeographic group of H. pylori. Results By real-time PCR, the prevalence of H. pylori infection among the 147 patients included was 57%. Culture was positive in only 29% of the cases. Twenty-seven percent of patients had received H. pylori eradication treatment. The primary and secondary resistance rates to clarithromycin were 23% and 36%, respectively, and to metronidazole, 45% and 71%, respectively. Only one isolate was resistant to levofloxacin, and no resistance to amoxicillin, tetracycline, and rifampicin was detected. A double population was present in 14 patients. The MLST analysis classified the 42 H. pylori strains from 38 patients in 2 haplotypes: hpEurope (33) and hpNEAfrica (9). Conclusion The prevalence of H. pylori remains high in Algeria but appears to be decreasing in recent years. High resistance to clarithromycin requires increased monitoring of the evolution of antibiotic resistance and adaptation of eradication therapy.

As Helicobacter pylori infects half the world's population and displays an extensive intraspecies diversity, genomics is a powerful tool to understand evolution and disease, to identify factors that confer higher risk of severe sequelae, and to find new approaches for therapy both among bacterial and host targets. In line with these objectives, this review article summarizes the major findings in Helicobacter genomics in papers published between April 2016 and March 2017.

The human gastric colonizer Helicobacter pylori is useful to track human migrations given the agreement between the bacterium phylogeographic distribution and human migrations. As Portugal was an African and Brazilian colonizer for over 400 years, we hypothesized that Portuguese isolates were likely genetically closer with those from countries colonized by Portuguese in the past. We aimed to characterize the population structure of several Portuguese-speaking countries, including Portugal, Brazil, Angola, and Cape Verde.We included strains isolated in Portugal from Portuguese and from former Portuguese colonies. These strains were typed by multilocus sequence typing (MLST) for seven housekeeping genes. We also retrieved from Multi Locus Sequence Typing Web site additional housekeeping gene sequences, namely from Angola and Brazil.We provided evidence that strains from Portuguese belong to hpEurope and that the introgression of hpEurope in non-European countries that speak Portuguese is low, except for Brazil and Cape Verde, where hpEurope accounted for one quarter and one half of the population, respectively. We found genetic similarity for all strains from Portuguese-speaking countries that belong to hpEurope population. Moreover, these strains showed a predominance of ancestral Europe 2 (AE2) over ancestral Europe 1 (AE1), followed by ancestral Africa 1.H. pylori is a useful marker even for relative recent human migration events and may become rapidly differentiated from founder populations. H. pylori from Portuguese-speaking countries assigned to hpEurope appears to be a hybrid population resulting from the admixture of AE1, AE2 and ancestral hpAfrica1.

Aims To understand whether the variability found in the proteome of Helicobacter pylori relates to the genomic methylation, virulence and associated gastric disease. Methods and Results We applied the Minimum-Common-Restriction-Modification (MCRM) algorithm to genomic methylation data of 30 Portuguese H. pylori strains, obtained by genome sensitivity to Type II restriction enzymes' digestion. All the generated dendrograms presented three clusters with no association with gastric disease. Comparative analysis of two-dimensional gel electrophoresis (2DE) maps obtained for total protein extracts of 10 of these strains, representative of the three main clusters, revealed that among 70 matched protein spots (in a universe of 300), 16 were differently abundant (P

The development of high-throughput whole genome sequencing (WGS) technologies is changing the face of microbiology, facilitating the comparison of large numbers of genomes from different lineages of a same organism. Our aim was to review the main advances on Helicobacter pylori “omics” and to understand how this is improving our knowledge of the biology, diversity and pathogenesis of H. pylori. Since the first H. pylori isolate was sequenced in 1997, 510 genomes have been deposited in the NCBI archive, providing a basis for improved understanding of the epidemiology and evolution of this important pathogen. This review focuses on works published between April 2015 and March 2016. Helicobacter “omics” is already making an impact and is a growing research field. Ultimately these advances will be translated into a routine clinical laboratory setting in order to improve public health.

Objectives Nuclear medicine (NM) is a rapidly developing field. In Portugal, no occupational study has been conducted yet that characterizes the professional profile of NM technologists (NMTs). We investigated the clinical tasks performed by NMTs in Portugal, analysing their practices with regard to radiation protection matters and their compliance with established international guidelines for best practice. Methods A questionnaire targeted at NMTs was constructed and distributed among 105 NMTs working in Portugal (an estimated 88% of the NMT population in Portugal). Questions addressed the demographic profile, academic background and professional profile of NMTs, with emphasis on practices adopted in NM tasks and radiation protection. Results In all, 51.4% of the 105 NMTs responded. The majority (70.4%) of the NMTs studied were women, with an average age of 34.3 (± 10.4) years and 11.6 (± 10.6) years of professional experience. The reported NM tasks included radiopharmaceutical preparation (96.3%), PET (44.4%), intravenous administration (74.1%), administration with dose containers (97.7%) and administration with syringe shields (76.9%). The use of a protective lead apron was rare (2.7%). The average individual dose recorded was 3.8 (± 2.7%) mSv/year. Conclusion NMTs in Portugal are generally young women with specialized academic education, consistent with the developments in NM technology and education in Portugal since the past decade. The majority of NMT activities are focused on conventional NM. The estimated annual average individual dose is below the established legal limit. However, radiation protection practices related to staff protection are not harmonized, revealing key aspects to be considered in future education and training.

© 2017 John Wiley & Sons Ltd., Background: Helicobacter pylori virulence is associated with different clinical outcomes. The existence of an intact dupA gene from tfs4b cluster has been suggested as a predictor for duodenal ulcer development. However, the role of tfs plasticity zone clusters in the development of ulcers remains unclear. We studied several H. pylori strains to characterize the gene arrangement of tfs3 and tfs4 clusters and their impact in the inflammatory response by infected gastric cells. Methods: The genome of 14 H. pylori strains isolated from Western patients, pediatric (n=10) and adult (n=4), was fully sequenced using the Illumina platform MiSeq, in addition to eight pediatric strains previously sequenced. These strains were used to infect human gastric cells, and the secreted interleukin-8 (IL-8) was quantified by ELISA. The expression of virB2, dupA, virB8, virB10, and virB6 was assessed by quantitative PCR in adherent and nonadherent fractions of H. pylori during in vitro co-infection, at different pH values. Results: We have found that cagA-positive H. pylori strains harboring a complete tfs plasticity zone cluster significantly induce increased production of IL-8 from gastric cells. We have also found that the region spanning from virB2 to virB10 genes constitutes an operon, whose expression is increased in the adherent fraction of bacteria during infection, as well as in both adherent and nonadherent fractions at acidic conditions. Conclusions: A complete tfs plasticity zone cluster is a virulence factor that may be important for the colonization of H. pylori and to the development of severe outcomes of the infection with cagA-positive strains., This work was supported by the FCT-PTDC/BIM-MEC/1051/2012 grant from the Fundação para a Ciência e a Tecnologia (FCT) (to M.O.). B.S. and F.F.V. are recipients of postdoctoral fellowships (PTDC/BIM- MEC/1051/2012 and SFRH/BPD/95125/2013, respectively) from FCT, and R.R is recipient of a fellowship (BRJ-DDI/2012) from the National Institute of Health. WGS and capillary sequencing were performed at Unidade de Tecnologia e Inovação (Departamento de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal).

Summary The distinction between pathogen elimination and damage limitation during infection is beginning to change perspectives on infectious disease control, and has recently led to the development of novel therapies that focus on reducing the illness caused by pathogens (‘‘damage limitation’’) rather than reducing pathogen burdens directly (‘‘pathogen elimination’’). While beneficial at the individual host level, the population consequences of these interventions remain unclear. To address this issue, we present a simple conceptual framework for damage limitation during infection that distinguishes between therapies that are either host-centric (pro-tolerance) or pathogen-centric (anti-virulence). We then draw on recent developments from the evolutionary ecology of disease tolerance to highlight some potential epidemiological and evolutionary responses of pathogens to medical interventions that target the symptoms of infection. Just as pathogens are known to evolve in response to antimicrobial and vaccination therapies, we caution that claims of ‘‘evolution-proof’’ anti-virulence interventions may be premature, and further, that in infections where virulence and transmission are linked, reducing illness without reducing pathogen burden could have non-trivial epidemiological and evolutionary consequences that require careful examination. Two Ways of Surviving

Considering the recommended indications for Helicobacter pylori (H. pylori) eradication therapy and the broad spectrum of available diagnostic methods, a reliable diagnosis is mandatory both before and after eradication therapy. Only highly accurate tests should be used in clinical practice, and the sensitivity and specificity of an adequate test should exceed 90%. The choice of tests should take into account clinical circumstances, the likelihood ratio of positive and negative tests, the cost-effectiveness of the testing strategy and the availability of the tests. This review concerns some of the most recent developments in diagnostic methods of H. pylori infection, namely the contribution of novel endoscopic evaluation methodologies for the diagnosis of H. pylori infection, such as magnifying endoscopy techniques and chromoendoscopy. In addition, the diagnostic contribution of histology and the urea breath test was explored recently in specific clinical settings and patient groups. Recent studies recommend enhancing the number of biopsy fragments for the rapid urease test. Bacterial culture from the gastric biopsy is the gold standard technique, and is recommended for antibiotic susceptibility test. Serology is used for initial screening and the stool antigen test is particularly used when the urea breath test is not available, while molecular methods have gained attention mostly for detecting antibiotic resistance.

Helicobacter pylori is a common human pathogen infecting about 30% of children and 60% of adults worldwide and is responsible for diseases such as gastritis, peptic ulcer and gastric cancer. Treatment against H. pylori is based on the use of antibiotics, but therapy failure can be higher than 20% and is essentially due to an increase in the prevalence of antibiotic-resistant bacteria, which has led to the search for alternative therapies. In this review, we discuss alternative therapies for H. pylori, mainly phytotherapy and probiotics. Probiotics are live organisms or produced substances that are orally administrated, usually in addition to conventional antibiotic therapy. They may modulate the human microbiota and promote health, prevent antibiotic side effects, stimulate the immune response and directly compete with pathogenic bacteria. Phytomedicine consists of the use of plant extracts as medicines or health-promoting agents, but in most cases the molecular mode of action of the active ingredients of these herbal extracts is unknown. Possible mechanisms include inhibition of H. pylori urease enzyme, disruption of bacterial cell membrane, and modulation of the host immune system. Other alternative therapies are also reviewed.

Helicobacter pylori chronically infects the gastric mucosa in more than half of the human population; in a subset of this population, its presence is associated with development of severe disease, such as gastric cancer. Genomic analysis of several strains has revealed an extensive H. pylori pan-genome, likely to grow as more genomes are sampled. Here we describe the draft genome sequence (63 contigs; 26× mean coverage) of H. pylori strain B45, isolated from a patient with gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The major finding was a 24.6-kb prophage integrated in the bacterial genome. The prophage shares most of its genes (22/27) with prophage region II of Helicobacter acinonychis strain Sheeba. After UV treatment of liquid cultures, circular DNA carrying the prophage integrase gene could be detected, and intracellular tailed phage-like particles were observed in H. pylori cells by transmission electron microscopy, indicating that phage production can be induced from the prophage. PCR amplification and sequencing of the integrase gene from 341 H. pylori strains from different geographic regions revealed a high prevalence of the prophage (21.4%). Phylogenetic reconstruction showed four distinct clusters in the integrase gene, three of which tended to be specific for geographic regions. Our study implies that phages may play important roles in the ecology and evolution of H. pylori., IMPORTANCE Helicobacter pylori chronically infects the gastric mucosa in more than half of the human population, and while most of the infected individuals do not develop disease, H. pylori infection doubles the risk of developing gastric cancer. An abundance and diversity of viruses (phages) infect microbial populations in most environments and are important mediators of microbial diversity. Our finding of a 24.6-kb prophage integrated inside an H. pylori genome and the observation of circular integrase gene-containing DNA and phage-like particles inside cells upon UV treatment demonstrate that we have discovered a viable H. pylori phage. The additional finding of integrase genes in a large proportion of screened isolates of diverse geographic origins indicates that the prevalence of prophages may have been underestimated in H. pylori. Since phages are important drivers of microbial evolution, the discovery should be important for understanding and predicting genetic diversity in H. pylori.

Helicobacter pylori is a Gram-negative microaerophilic bacterium that has colonized the human gastric mucosa. This infection is very common and affects more than half of the human population. The prevalence is however unbalanced between rural developing areas (more than 80%) and urban developed areas (less than 40%). H. pylori is responsible for several pathologies, such as gastritis, peptic ulcer and gastric cancer but its transmission pathway is still not clear. The risk factors for H. pylori infection include poor social and economic development; poor hygienic practices; absence of hygienic drinking water; and unsanitary prepared food. There is evidence supporting a gastro-oral, oral-oral and faecal-oral transmission, but no predominant mechanism of transmission has been yet identified. Transmission may occur in a vertical mode (e.g. from parents to child) or in a horizontal mode (across individuals or from environmental contamination). In either case, the involvement of water and food cannot be excluded as vehicles or sources of infection. Indirect evidence of presence of H. pylori in water and food, namely the detection of its DNA and survival studies after artificial contamination of food and water has been described. This paper reviews data both favourable and against the role of water and food in the transmission of H. pylori, exploring their role as a potential transmission vehicle for person-to-person and food-chain transmission. The likelihood of the transmission pathway in developing rural and developed urban areas appears to be different. In developed areas, person-to-person transmission within families appears to be dominant, while in the rural developing areas the transmission pathway appears to be more complex. In this later case, the transmission by contaminated food, water, or via intensive contact between infants and non-parental caretakers may have a greater influence than within-family transmission.

Background Helicobacter pylori colonizes the human stomach and is associated with gastritis, peptic ulcer, and gastric cancer. This ubiquitous association between H. pylori and humans is thought to be present since the origin of modern humans. The H. pylori genome encodes for an exceptional number of restriction and modifications (R-M) systems. To evaluate if R-M systems are an adequate tool to determine the geographic distribution of H. pylori strains, we typed 221 strains from Africa, America, Asia, and Europe, and evaluated the expression of different 29 methyltransferases. Results Independence tests and logistic regression models revealed that ten R-M systems correlate with geographical localization. The distribution pattern of these methyltransferases may have been originated by co-divergence of regional H. pylori after its human host migrated out of Africa. The expression of specific methyltransferases in the H. pylori population may also reflect the genetic and cultural background of its human host. Methyltransferases common to all strains, M. HhaI and M. NaeI, are likely conserved in H. pylori, and may have been present in the bacteria genome since the human diaspora out of Africa. Conclusion This study indicates that some methyltransferases are useful geomarkers, which allow discrimination of bacterial populations, and that can be added to our tools to investigate human migrations., This work was partially supported by New England Biolabs, Inc. (USA)

The genome sequences of three Helicobacter pylori strains revealed an abundant number of putative restriction and modification (R-M) systems within a small genome (1.60 to 1.67 Mb). Each R-M system includes an endonuclease that cleaves a specific DNA sequence and a DNA methyltransferase that methylates either adenosine or cytosine within the same DNA sequence. These are believed to be a defense mechanism, protecting bacteria from foreign DNA. They have been classified as selfish genetic elements; in some instances it has been shown that they are not easily lost from their host cell. Possibly because of this phenomenon, the H. pylori genome is very rich in R-M systems, with considerable variation in potential recognition sequences. For this reason the protective aspect of the methyltransferase gene has been proposed as a tool for typing H. pylori isolates. We studied the expression of H. pylori methyltransferases by digesting the genomic DNAs of 50 strains with 31 restriction endonucleases. We conclude that methyltransferase diversity is sufficiently high to enable the use of the genomic methylation status as a typing tool. The stability of methyltransferase expression was assessed by comparing the methylation status of genomic DNAs from strains that were isolated either from the same patient at different times or from different stomach locations (antrum and corpus). We found a group of five methyltransferases common to all tested strains. These five may be characteristic of the genetic pool analyzed, and their biological role may be important in the host/bacterium interaction., This work was partially supported by New England Biolabs, Inc.

Helicobacter pylori (H. pylori) successfully colonizes the human stomach of the majority of the human population. This infection always causes chronic gastritis, but may evolve to serious outcomes, such as peptic ulcer, gastric carcinoma or mucosa-associated lymphoid tissue lymphoma. H. pylori first line therapy recommended by the Maastricht-4 Consensus Report comprises the use of two antibiotics and a proton-pomp inhibitor, but in some regions failure associated with this treatment is already undesirable high. Indeed, treatment failure is one of the major problems associated with H. pylori infection and is mainly associated with bacterial antibiotic resistance. In order to counteract this situation, some effort has been allocated during the last years in the investigation of therapeutic alternatives beyond antibiotics. These include vaccines, probiotics, photodynamic inactivation and phage therapy, which are briefly revisited in this review. A particular focus on phytomedicine, also described as herbal therapy and botanical therapy, which consists in the use of plant extracts for medicinal purposes, is specifically addressed, namely considering its history, category of performed studies, tested compounds, active principle and mode of action. The herbs already experienced are highly diverse and usually selected from products with a long history of employment against diseases associated with H. pylori infection from each country own folk medicine. The studies demonstrated that many phytomedicine products have an anti-H. pylori activity and gastroprotective action. Although the mechanism of action is far from being completely understood, current knowledge correlates the beneficial action of herbs with inhibition of essential H. pylori enzymes, modulation of the host immune system and with attenuation of inflammation.