Helicobacter Pylori's Plasticity Zones Are Novel Transposable Elements

BACKGROUND:Genes present in only certain strains of a bacterial species can strongly affect cellular phenotypes and evolutionary potentials. One segment that seemed particularly rich in strain-specific genes was found by comparing the first two sequenced Helicobacter pylori genomes (strains 26695 and J99) and was named a "plasticity zone". PRINCIPAL FINDINGS:We studied the nature and evolution of plasticity zones by sequencing them in five more Helicobacter strains, determining their locations in additional strains, and identifying them in recently released genome sequences. They occurred as discrete units, inserted at numerous chromosomal sites, and were usually flanked by direct repeats of 5'AAGAATG, a sequence generally also present in one copy at unoccupied sites in other strains. This showed that plasticity zones are transposable elements, to be called TnPZs. Each full length TnPZ contained a cluster of type IV protein secretion genes (tfs3), a tyrosine recombinase family gene ("xerT"), and a large (>or=2800 codon) orf encoding a protein with helicase and DNA methylase domains, plus additional orfs with no homology to genes of known function. Several TnPZ types were found that differed in gene arrangement or DNA sequence. Our analysis also indicated that the first-identified plasticity zones (in strains 26695 and J99) are complex mosaics of TnPZ remnants, formed by multiple TnPZ insertions, and spontaneous and transposable element mediated deletions. Tests using laboratory-generated deletions showed that TnPZs are not essential for viability, but identified one TnPZ that contributed quantitatively to bacterial growth during mouse infection and another that affected synthesis of proinflammatory cytokines in cell culture. CONCLUSIONS:We propose that plasticity zone genes are contained in conjugative transposons (TnPZs) or remnants of them, that TnPZ insertion is mediated by XerT recombinase, and that some TnPZ genes affect bacterial phenotypes and fitness

Interleukin-1 beta single-nucleotide polymorphism\u27s C allele is associated with elevated risk of gastric cancer in helicobacter pylori-infected Peruvians

Particular alleles of the interleukin-1B (IL-1B) gene have been correlated with increased risk of atrophic gastritis and gastric cancer in the populations of East Asia and Europe. No such data exist from Peru, a developing country with a population genotypically different from others studied and with a high prevalence of Helicobacter pylori infection and gastric cancer. We conducted a case-control study comparing 334 hospitalized patients with atrophic gastritis or gastric cancer with 158 nonatrophic gastritis patients (controls). Conditional logistic regression analysis revealed that an increased risk of atrophic gastritis (odds ratio, 5.60) and gastric cancer (odds ratio, 2.36) was associated with the IL-1B-511 C allele. Our study is the first to establish this allele as a risk for these conditions. Given the high prevalence of H. pylori and recurrence rate after treatment, IL-1B-511 single-nucleotide polymorphism analysis may identify those individuals who would benefit most from robust H. pylori eradication efforts in Peru

LPG stove and fuel intervention among pregnant women reduce fine particle air pollution exposures in three countries: Pilot results from the HAPIN trial

The Household Air Pollution Intervention Network trial is a multi-country study on the effects of a liquefied petroleum gas (LPG) stove and fuel distribution intervention on women's and children's health. There is limited data on exposure reductions achieved by switching from solid to clean cooking fuels in rural settings across multiple countries. As formative research in 2017, we recruited pregnant women and characterized the impact of the intervention on personal exposures and kitchen levels of fine particulate matter (PM2.5) in Guatemala, India, and Rwanda. Forty pregnant women were enrolled in each site. We measured cooking area concentrations of and personal exposures to PM2.5 for 24 or 48 h using gravimetric-based PM2.5 samplers at baseline and two follow-ups over two months after delivery of an LPG cookstove and free fuel supply. Mixed models were used to estimate PM2.5 reductions. Median kitchen PM2.5 concentrations were 296 μg/m3 at baseline (interquartile range, IQR: 158-507), 24 μg/m3 at first follow-up (IQR: 18-37), and 23 μg/m3 at second follow-up (IQR: 14-37). Median personal exposures to PM2.5 were 134 μg/m3 at baseline (IQR: 71-224), 35 μg/m3 at first follow-up (IQR: 23-51), and 32 μg/m3 at second follow-up (IQR: 23-47). Overall, the LPG intervention was associated with a 92% (95% confidence interval (CI): 90-94%) reduction in kitchen PM2.5 concentrations and a 74% (95% CI: 70-79%) reduction in personal PM2.5 exposures. Results were similar for each site. CONCLUSIONS: The intervention was associated with substantial reductions in kitchen and personal PM2.5 overall and in all sites. Results suggest LPG interventions in these rural settings may lower exposures to the WHO annual interim target-1 of 35 μg/m3. The range of exposure contrasts falls on steep sections of estimated exposure-response curves for birthweight, blood pressure, and acute lower respiratory infections, implying potentially important health benefits when transitioning from solid fuels to LPG

Links between sex-related expectations about alcohol, heavy episodic drinking and sexual risk among young men in a shantytown in Lima, Peru

CONTEXT: Alcohol use is frequently identified as a contributor to risky sexual behaviors; however, research results are mixed. Given the conflicting evidence, researchers have focused on other factors, such as expectations about alcohol's effects that might help explain the relationship of alcohol use and risky sexual behaviors. METHODS: Cross-sectional data from 312 sexually experienced males aged 18-30 in a shantytown in Lima, Peru, were used in logistic regression models to identify associations of heavy episodic drinking and sex-related expectations about alcohol with sexual risk behaviors. RESULTS: Heavy episodic drinking was associated with having had two or more sexual partners and having had sex with a casual partner in the past year (odds ratios, 2.8 and 2.5, respectively). After controlling for alcohol consumption, sex-related expectations about alcohol were associated with these high-risk sexual behaviors, as well as with not using a condom at last sex (1.2) and not using a condom at last sex with a casual partner (1.3). CONCLUSION: Beliefs about the effect of alcohol on sexual performance could help explain links between alcohol consumption and risky sexual behavior not completely accounted for by the pharmacological effects of alcohol

Gender differences in sex-related alcohol expectancies in young adults from a peri-urban area in Lima, Peru

OBJECTIVES: To estimate the effect of sex-related alcohol expectancies (SRAE) on hazardous drinking prevalence and examine gender differences in reporting SRAE. METHODS: Trained research assistants administered part of a questionnaire to 393 men and 400 women between 18 and 30 years old from a peri-urban shantytown in Lima, Peru. The remaining questions were self-administered. Two measuring instruments-one testing for hazardous drinking and one for SRAE-were used. Multivariate data analysis was performed using logistic regression. RESULTS: Based on odds ratios adjusted for socio-demographic variables (age, marital status, education, and employment status) (n = 793), men with one or two SRAE and men with three or more SRAE were 2.3 (95% confidence interval (CI) = 1.4-3.8; p = 0.001) and 3.9 (95% CI = 2.1-7.3; p < 0.001) times more likely than men with no SRAE, respectively, to be hazardous drinkers. Reporting of SRAE was significantly higher in men versus women. CONCLUSION: In a shantytown in Lima, SRAE is associated with hazardous drinking among men, but not among women, and reporting of SRAE differs by gender

Effectiveness of Enterobacterial Repetitive Intergenic Consensus PCR and Random Amplified Polymorphic DNA Fingerprinting for Helicobacter pylori Strain Differentiation

We compared the robustness and discriminatory power of the enterobacterial repetitive intergenic consensus (ERIC) and random amplified polymorphic DNA (RAPD) fingerprinting methods for detecting cases of mixed Helicobacter pylori infection in Peruvian shantytown residents. H. pylori isolates from 63 participants were cultured, and five single colonies and a pool of additional colonies from each participant were analyzed by ERIC-PCR and by RAPD tests with four 10-nucleotide primers (one primer per reaction). There was 94% agreement between the ERIC and RAPD profiles in classifying sets of isolates as uniform versus closely related but not identical versus probably unrelated, indicating a high kappa statistic of 0.8942. Subtle differences in related ERIC or RAPD patterns likely reflect gene transfer between strains, recombination, and/or mutation, whereas markedly different patterns reflect infection by unrelated strains. At least half of infected shantytown residents seemed to carry more than one H. pylori strain, although in 19 of 31 persons, the strains were closely related. Three RAPD tests, each with a different primer, were needed to achieve the sensitivity of one ERIC test. ERIC-PCR constitutes a resource- and time-efficient method for H. pylori strain differentiation

Validation of String Test for Diagnosis of Helicobacter pylori Infections

The method of recovering Helicobacter pylori DNA or viable cells absorbed on a string that a person has swallowed and that is retrieved an hour later (string test) should be a useful alternative to traditional analysis of cells or DNA obtained by endoscopy, which is invasive, uncomfortable, relatively costly, and ill-suited for community-based and pediatric studies. Here we assayed the sensitivity and validity of the string test versus conventional endoscopic biopsy for detecting and analyzing H. pylori infection. Forty-four people with gastric complaints were studied using both H. pylori culture and urease gene (ureB) PCR. H. pylori organisms cultured from strings and biopsy specimens from the same patients were fingerprinted by the randomly amplified polymorphic DNA (RAPD) method. Biopsy sections were also hematoxylin and eosin and silver stained for H. pylori detection. H. pylori was cultured from 80% of strings and detected by PCR from 91% of strings from participants whose biopsies had been H. pylori positive by culture, PCR, and/or histology. Strains recovered from strings and biopsy specimens yielded identical or closely related RAPD profiles in each of the 24 cases tested. We conclude that the string test is a useful method for H. pylori recovery and analysis when relatively noninvasive procedures are needed

Autosome STRs in Native South America-Testing Models of Association With Geography and Language

Information on one Ecuadorian and three Peruvian Amerindian populations for 11 autosomal short tandem repeat (STR) loci is presented and incorporated in analyses that includes 26 other Native groups spread all over South America. Although in comparison with other studies we used a reduced number of markers, the number of populations included in our analyses is currently unmatched by any genome-wide dataset. The genetic polymorphisms indicate a clear division of the populations into three broad geographical areas: Andes, Amazonia, and the Southeast, which includes the Chaco and southern Brazil. The data also show good agreement with proposed hypotheses of splitting and dispersion of major language groups over the last 3,000 years. Therefore, relevant aspects of Native American history can be traced using as few as 11 STR autosomal markers coupled with a broad geographic distribution of sampled populations. Am J Phys Anthropol 145: 371-381, 2011. (C) 2011 Wiley-Liss, Inc

Chronic exposure to biomass fuel smoke and markers of endothelial inflammation

Indoor smoke exposure may affect cardiovascular disease (CVD) risk via lung-mediated inflammation, oxidative stress, and endothelial inflammation. We sought to explore the association between indoor smoke exposure from burning biomass fuels and a selected group of markers for endothelial inflammation. We compared serum concentrations of amyloid A protein, E-selectin, soluble ICAM-1 and VCAM-1, von Willebrand factor (VWF), and high sensitivity C-reactive protein (hs-CRP) in 228 biomass exposed vs. 228 non-exposed participants living in Puno, Peru. Average age was 56 years (SD=13), average BMI was 26.5 kg/m(2) (SD=4.4), 48% were male, 59.4% completed high school and 2% reported a physician diagnosis of CVD. In unadjusted analysis, serum levels of soluble ICAM-1 (330 vs. 302 ng/mL; p<0.001), soluble VCAM-1 (403 vs. 362 ng/mL; p<0.001), and E-selectin (54.2 vs. 52.7 ng/mL; p=0.05) were increased in biomass exposed vs. non-exposed participants, respectively; whereas serum levels of vWF (1148 vs. 1311 mU/mL; p<0.001) and hs-CRP (2.56 vs. 3.12 mg/L; p<0.001) were decreased, respectively. In adjusted analyses, chronic exposure to biomass fuels remained positively associated with serum levels of soluble ICAM-1 (p=0.03) and VCAM-1 (p=0.05) and E-selectin (p=0.05), and remained negatively associated with serum levels of vWF (p=0.02) and hs-CRP (p<0.001). Daily exposure to biomass fuel smoke was associated with important differences in specific biomarkers of endothelial inflammation and may help explain accelerated atherosclerosis among those who are chronically exposed

DNA-Level Diversity and Relatedness of Helicobacter pylori Strains in Shantytown Families in Peru and Transmission in a Developing-Country Setting▿

The efficiency of transmission of a pathogen within families compared with that between unrelated persons can affect both the strategies needed to control or eradicate infection and how the pathogen evolves. In industrialized countries, most cases of transmission of the gastric pathogen Helicobacter pylori seems to be from mother to child. An alternative model, potentially applicable among the very poor in developing countries, where infection is more common and the sanitary infrastructure is often deficient, invokes frequent transmission among unrelated persons, often via environmental sources. In the present study, we compared the genotypes of H. pylori from members of shantytown households in Peru to better understand the transmission of H. pylori in developing-country settings. H. pylori cultures and/or DNAs were obtained with informed consent by the string test (a minimally invasive alternative to endoscopy) from at least one child and one parent from each of 62 families. The random amplified polymorphic DNA fingerprints of 57 of 81 (70%) child-mother strain pairs did not match, nor did the diagnostic gene sequences (>1% DNA sequence difference), independent of the child's age (range, 1 to 39 years). Most strains from siblings or other paired family members were also unrelated. These results suggest that H. pylori infections are often community acquired in the society studied. Transmission between unrelated persons should facilitate the formation of novel recombinant genotypes by interstrain DNA transfer and selection for genotypes that are well suited for individual hosts. It also implies that the effective prevention of H. pylori infection and associated gastroduodenal disease will require anti-H. pylori measures to be applied communitywide