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1.
Lab Invest ; 104(2): 100310, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38135155

RESUMEN

Diagnostic methods for Helicobacter pylori infection include, but are not limited to, urea breath test, serum antibody test, fecal antigen test, and rapid urease test. However, these methods suffer drawbacks such as low accuracy, high false-positive rate, complex operations, invasiveness, etc. Therefore, there is a need to develop simple, rapid, and noninvasive detection methods for H. pylori diagnosis. In this study, we propose a novel technique for accurately detecting H. pylori infection through machine learning analysis of surface-enhanced Raman scattering (SERS) spectra of gastric fluid samples that were noninvasively collected from human stomachs via the string test. One hundred participants were recruited to collect gastric fluid samples noninvasively. Therefore, 12,000 SERS spectra (n = 120 spectra/participant) were generated for building machine learning models evaluated by standard metrics in model performance assessment. According to the results, the Light Gradient Boosting Machine algorithm exhibited the best prediction capacity and time efficiency (accuracy = 99.54% and time = 2.61 seconds). Moreover, the Light Gradient Boosting Machine model was blindly tested on 2,000 SERS spectra collected from 100 participants with unknown H. pylori infection status, achieving a prediction accuracy of 82.15% compared with qPCR results. This novel technique is simple and rapid in diagnosing H. pylori infection, potentially complementing current H. pylori diagnostic methods.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/diagnóstico , Espectrometría Raman , Estómago , Ureasa/análisis , Sensibilidad y Especificidad
2.
Crit Rev Microbiol ; : 1-30, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38910506

RESUMEN

Helicobacter pylori is a gram-negative bacterium that colonizes the stomach of approximately half of the worldwide population, with higher prevalence in densely populated areas like Asia, the Caribbean, Latin America, and Africa. H. pylori infections range from asymptomatic cases to potentially fatal diseases, including peptic ulcers, chronic gastritis, and stomach adenocarcinoma. The management of these conditions has become more difficult due to the rising prevalence of drug-resistant H. pylori infections, which ultimately lead to gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. In 1994, the International Agency for Research on Cancer (IARC) categorized H. pylori as a Group I carcinogen, contributing to approximately 780,000 cancer cases annually. Antibiotic resistance against drugs used to treat H. pylori infections ranges between 15% and 50% worldwide, with Asian countries having exceptionally high rates. This review systematically examines the impacts of H. pylori infection, the increasing prevalence of antibiotic resistance, and the urgent need for accurate diagnosis and precision treatment. The present status of precision treatment strategies and prospective approaches for eradicating infections caused by antibiotic-resistant H. pylori will also be evaluated.

3.
BMC Microbiol ; 23(1): 360, 2023 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-37993791

RESUMEN

BACKGROUND: Helicobacter pylori lipopolysaccharide (LPS) structures vary among strains of different geographic origin. The aim of this study was to characterize the LPS O-antigen profiles of H. pylori strains isolated from Southwest China, and to further analyze the association of Lewis antigen expression with clinical outcomes and antibiotic resistance. RESULTS: A total of 71 H. pylori isolates from Southwest China were included for LPS profiling by silver staining and Western blotting after SDS-PAGE electrophoresis. We demonstrated that all the clinical isolates had the conserved lipid A and core-oligosaccharide, whereas the O-antigen domains varied significantly among the isolates. Compared with the common presence of the glucan/heptan moiety in LPS O-antigen structure of European strains, the clinical isolates in this study appeared to lack the glucan/heptan moiety. The expression frequency of Lex, Ley, Lea, and Leb was 66.2% (47/71), 84.5% (60/71), 56.3% (40/71), and 31.0% (22/71), respectively. In total, the expression of type II Lex and/or Ley was observed in 69 (97.2%) isolates, while type I Lea and/or Leb were expressed in 49 (69.0%) isolates. No association of Lewis antigen expression with clinical outcomes or with antibiotic resistance was observed. CONCLUSIONS: H. pylori strains from Southwest China tend to produce heptan-deficient LPS and are more likely to express type I Lewis antigens as compared with Western strains. This may suggest that H. pylori evolves to change its LPS structure for adaptation to different hosts.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Humanos , Lipopolisacáridos/metabolismo , Antígenos O , Antígenos del Grupo Sanguíneo de Lewis/metabolismo , Glucanos
4.
Helicobacter ; 28(4): e12985, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37066609

RESUMEN

BACKGROUND: As the reduced eradication rate of Helicobacter pylori (H. pylori), we introduced string-test and quantitative PCR (qPCR) for susceptibility-guided therapy innovatively. The practicality of the string test was evaluated. METHODS: It was an open-label, non-randomized, parallel, single-center study, in which subjects tested by 13 C- urea breath test (UBT) and string-qPCR were enrolled. Based on the results of string-qPCR, we calculated clarithromycin and levofloxacin resistance rates and gave 13 C-UBT positive patients 14 days susceptibility-guided bismuth quadruple therapy. In the empirical therapy group, we retrospectively analyzed the treatment results of 13 C-UBT positive patients also treated with bismuth quadruple at Shenzhen Luohu People's Hospital from January 2021 to May 2022. The eradication rate was compared between susceptibility-guided therapy and empirical therapy groups. RESULTS: The diagnosis of H. pylori infection using the string-qPCR had an overall concordance rate of 95.9% with the 13 C-UBT results. Based on the results of string-qPCR, the clarithromycin and levofloxacin resistance rates were 26.1% and 31.8%, respectively. The patients who were given 14 days susceptibility-guided bismuth-based quadruple therapy achieved a high H. pylori eradication rate of 91.8%. Retrospective analysis of patient treatment data from January 2021 to May 2022 available in the hospital database revealed an overall success rate of 82.3% for those who received empirical bismuth-based quadruple therapies, which is marginally significantly lower than that of the string-qPCR susceptibility-guided group (p = 0.084). CONCLUSION: The high treatment success rate of 91.8% indicates that the string-qPCR test is a valuable and feasible approach for clinical practice to help improve H. pylori treatment success rate.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Humanos , Amoxicilina/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bismuto/uso terapéutico , Claritromicina/farmacología , Claritromicina/uso terapéutico , Quimioterapia Combinada , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/genética , Levofloxacino/farmacología , Levofloxacino/uso terapéutico , Reacción en Cadena de la Polimerasa , Estudios Retrospectivos , Resultado del Tratamiento
5.
Int J Mol Sci ; 24(14)2023 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-37511140

RESUMEN

Helicobacter pylori has a unique lipopolysaccharide structure that is essential in maintaining its cell envelope integrity and imbues the bacterium with natural resistance to cationic antimicrobial peptides (CAMPs). Our group has recently elucidated the complete set of LPS glycosyltransferase genes in H. pylori reference strain G27. Here, with a series of eight systematically constructed LPS glycosyltransferase gene mutants (G27ΔHP1578, G27ΔHP1283, G27ΔHP0159, G27ΔHP0479, G27ΔHP0102, G27ΔwecA, G27ΔHP1284 and G27ΔHP1191), we investigated the roles of H. pylori LPS glycosyltransferases in maintaining cell morphology, cell wall permeability, and antimicrobial susceptibilities. We demonstrated that deletion of these LPS glycosyltransferase genes did not interfere with bacterial cell wall permeability, but resulted in significant morphological changes (coccoid, coiled "c"-shape, and irregular shapes) after 48 h growth as compared to the rod-like cell shape of the wild-type strain. Moreover, as compared with the wild-type, none of the LPS mutants had altered susceptibility against clarithromycin, levofloxacin, amoxicillin, tetracycline, and metronidazole. However, the deletion of the conserved LPS glycosyltransferases, especially the O-antigen-initiating enzyme WecA, displayed a dramatic increase in susceptibility to the CAMP polymyxin B and rifampicin. Taken together, our findings suggest that the LPS glycosyltransferases play critical roles in the maintenance of the typical spiral morphology of H. pylori, as well as resistance to CAMPs and rifampicin. The LPS glycosyltransferases could be promising targets for developing novel anti-H. pylori drugs.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Humanos , Lipopolisacáridos , Helicobacter pylori/genética , Glicosiltransferasas/genética , Rifampin , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Metronidazol , Amoxicilina , Claritromicina , Pared Celular , Péptidos Catiónicos Antimicrobianos , Permeabilidad , Infecciones por Helicobacter/microbiología
6.
J Infect Dis ; 226(Suppl 5): S486-S492, 2022 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-36478248

RESUMEN

BACKGROUND: Helicobacter pylori infection is an infectious disease and thus the eradication treatment should be guided by susceptibility testing. This study aimed to assess the applicability of broth microdilution as a routine susceptibility testing method for H. pylori. METHODS: Susceptibility profiles of clarithromycin (CLR) and levofloxacin (LEV) resistance in 76 clinical H. pylori isolates were simultaneously assessed using agar dilution and broth microdilution methods. The correlation between the minimum inhibitory concentrations (MICs) obtained by the 2 methods was assessed by means of linear regression analysis. RESULTS: The correlation between the MICs determined by broth microdilution method and agar dilution method was good for both CLR (r = 0.966) and LEV (r = 0.959). The susceptibility agreement between the 2 methods was 100% for CLR and 96.1% for LEV. Using the broth microdilution method, the false resistance was found in 3.9% (3 of 76) strains for LEV susceptibility testing. No false susceptibility was found for either CLR or LEV, and no false resistance was found for susceptibility testing of CLR. CONCLUSIONS: The broth microdilution method is suitable for routine susceptibility testing of clinical H. pylori isolates.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Humanos
7.
J Infect Dis ; 226(Suppl 5): S479-S485, 2022 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-36478247

RESUMEN

BACKGROUND: The aim of this study was to evaluate the rifamycin cross-resistance in Helicobacter pylori, and whether the use of rifampicin E-test strips to screen H. pylori rifabutin resistance is appropriate. METHODS: A total of 89 H. pylori isolates were included. Rifampicin minimum inhibitory concentrations (MICs) were obtained by E-test, while the MICs for rifapentine, rifaximin, and rifabutin were determined by agar dilution method. The rifamycin resistance rates based on different breakpoints were compared. Isolates with high-level rifampicin resistance were subjected to whole-genome sequencing. RESULTS: A wide distribution of MICs (mostly in the range 0.125-8 mg/L) was observed for rifampicin, rifapentine, and rifaximin. Using MIC >1, ≥ 4, and > 4 mg/L as the breakpoints, resistance rates to rifampicin/rifapentine/rifaximin were 60.4%/48.3%/38.2%, 28.1%/25.8%/23.6%, and 15.7%/16.9%/7.9%, respectively. However, the rifabutin MICs of all the tested H. pylori isolates were extremely low (≤0.016 mg/L). Applying MIC ≥ 0.125 mg/L as the breakpoint, rifabutin resistance was nil. No mutation was found in the rpoB gene sequences of the 2 isolates with high-level rifampicin resistance. CONCLUSIONS: There is a lack of cross-resistance between rifabutin and other rifamycins in H. pylori. The use of rifampicin E-test to predict H. pylori rifabutin resistance is inappropriate.


Asunto(s)
Helicobacter pylori , Rifabutina , Rifabutina/farmacología , Helicobacter pylori/genética
8.
BMC Microbiol ; 22(1): 196, 2022 08 13.
Artículo en Inglés | MEDLINE | ID: mdl-35964011

RESUMEN

BACKGROUND: The prevalence of Helicobacter pylori antibiotic susceptibility in the Tibet Autonomous Region, China is not determined. This study aimed to evaluate the antibiotic resistance patterns of H. pylori isolates there. RESULTS: A total of 153 (38.5%) H. pylori strains were successfully isolated from 397 patients in People's Hospital of Tibet Autonomous Region, China. The overall resistance rates were as follows: clarithromycin (27.4%), levofloxacin (31.3%), metronidazole (86.2%), amoxicillin (15.6%), tetracycline (0%), furazolidone (0.6%), and rifampicin (73.2%). Only 2.0% of H. pylori isolates were susceptible to all tested antimicrobials, with mono resistance, dual resistance, triple resistance, quadruple resistance, and quintuple resistance being 18.3%, 44.4%, 18.3%, 12.4%, and 4.6%, respectively. The resistance rates to levofloxacin (40.5%) and amoxicillin (21.5%) in strains isolated from female patients were significantly higher than those from male patients (21.6% and 9.5%, respectively). CONCLUSIONS: This study demonstrates high H. pylori resistance rates to clarithromycin, levofloxacin, metronidazole, and rifampicin, whereas moderate resistance to amoxicillin, and negligible resistant to tetracycline, and furazolidone in Tibet Autonomous Region, China. The high resistance to rifampicin warns further investigation of its derivative, rifabutin.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Amoxicilina , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , China/epidemiología , Claritromicina , Farmacorresistencia Bacteriana , Femenino , Furazolidona , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/epidemiología , Humanos , Levofloxacino , Masculino , Metronidazol , Pruebas de Sensibilidad Microbiana , Rifampin , Tetraciclina/farmacología , Tibet/epidemiología
9.
Helicobacter ; 27(2): e12873, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35151236

RESUMEN

BACKGROUND AND AIMS: As with other infectious diseases, Helicobacter pylori eradication regimens should be guided by susceptibility testing to achieve excellent success rate, especially in the era of high antibiotic resistance. However, susceptibility testing for H. pylori is rarely performed, which can be partly ascribed to the current lack of standardization of testing methods and the lack of unified consensus on the antibiotic resistance breakpoints. The aim of this review was to call for an international consensus on standardization and harmonization of H. pylori susceptibility testing. METHODS: We summarize and compare the advantages and disadvantages of four different phenotypic antimicrobial susceptibility testing (AST) methods (agar dilution, E-test, disk diffusion, and broth microdilution) and the molecular susceptibility testing method for H. pylori. RESULTS: The standard phenotypic testing methods and the molecular testing methods have their own advantages and disadvantages. Compared to the standard phenotypic methods, the molecular testing method does not require successful H. pylori culture, and therefore, is much more rapid and convenient for clinical use. However, the currently available molecular testing method is only suitable for detecting clarithromycin and quinolone susceptibility profiles in H. pylori. Although the standard AST is time-consuming, it is currently the only way to test the susceptibility of H. pylori to all the commonly used antibiotics. CONCLUSION: To make H. pylori susceptibility testing become a clinical routine, an international consensus on standardization and harmonization of H. pylori AST is needed. Future efforts are needed for optimizing broth culture of H. pylori, and developing commercial AST plates for achieving high throughput and automated susceptibility testing for H. pylori.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Claritromicina , Farmacorresistencia Bacteriana , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Pruebas de Sensibilidad Microbiana , Estándares de Referencia
10.
Biomed Eng Online ; 21(1): 1, 2022 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-34983542

RESUMEN

OBJECTIVE: Bowel sounds (BS) carry useful information about gastrointestinal condition and feeding status. Interest in computerized bowel sound-based analysis has grown recently and techniques have evolved rapidly. An important first step for these analyses is to extract BS segments, whilst neglecting silent periods. The purpose of this study was to develop a convolutional neural network-based BS detector able to detect all types of BS with accurate time stamps, and to investigate the effect of food consumption on some acoustic features of BS with the proposed detector. RESULTS: Audio recordings from 40 volunteers were collected and a BS dataset consisting of 6700 manually labelled segments was generated for training and testing the proposed BS detector. The detector attained 91.06% and 90.78% accuracy for the validation dataset and across-subject test dataset, respectively, with a well-balanced sensitivity and specificity. The detection rates evaluated on different BS types were also satisfactory. Four acoustic features were evaluated to investigate the food effect. The total duration and spectral bandwidth of BS showed significant differences before and after food consumption, while no significant difference was observed in mean-crossing rate values. CONCLUSION: We demonstrated that the proposed BS detector is effective in detecting all types of BS, and providing an accurate time stamp for each BS. The characteristics of BS types and the effect on detection accuracy is discussed. The proposed detector could have clinical application for post-operative ileus prognosis, and monitoring of food intake.


Asunto(s)
Acústica , Redes Neurales de la Computación , Recolección de Datos , Ingestión de Alimentos , Humanos , Complicaciones Posoperatorias
11.
PLoS Genet ; 15(11): e1008497, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31747390

RESUMEN

The lipopolysaccharide O-antigen structure expressed by the European Helicobacter pylori model strain G27 encompasses a trisaccharide, an intervening glucan-heptan and distal Lewis antigens that promote immune escape. However, several gaps still remain in the corresponding biosynthetic pathway. Here, systematic mutagenesis of glycosyltransferase genes in G27 combined with lipopolysaccharide structural analysis, uncovered HP0102 as the trisaccharide fucosyltransferase, HP1283 as the heptan transferase, and HP1578 as the GlcNAc transferase that initiates the synthesis of Lewis antigens onto the heptan motif. Comparative genomic analysis of G27 lipopolysaccharide biosynthetic genes in strains of different ethnic origin revealed that East-Asian strains lack the HP1283/HP1578 genes but contain an additional copy of HP1105 and JHP0562. Further correlation of different lipopolysaccharide structures with corresponding gene contents led us to propose that the second copy of HP1105 and the JHP0562 may function as the GlcNAc and Gal transferase, respectively, to initiate synthesis of the Lewis antigen onto the Glc-Trio-Core in East-Asian strains lacking the HP1283/HP1578 genes. In view of the high gastric cancer rate in East Asia, the absence of the HP1283/HP1578 genes in East-Asian H. pylori strains warrants future studies addressing the role of the lipopolysaccharide heptan in pathogenesis.


Asunto(s)
Infecciones por Helicobacter/genética , Lipopolisacáridos/genética , Antígenos O/genética , Neoplasias Gástricas/genética , Pueblo Asiatico , Fucosiltransferasas/genética , Fucosiltransferasas/inmunología , Glucanos/genética , Glicosiltransferasas/genética , Glicosiltransferasas/inmunología , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/genética , Helicobacter pylori/inmunología , Helicobacter pylori/patogenicidad , Humanos , Antígenos del Grupo Sanguíneo de Lewis/genética , Antígenos del Grupo Sanguíneo de Lewis/inmunología , Lipopolisacáridos/química , Lipopolisacáridos/inmunología , Mutagénesis , Antígenos O/inmunología , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/patología
12.
BMC Med ; 19(1): 73, 2021 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-33750355

RESUMEN

BACKGROUND: Maternal folic acid (FA) supplementation before and in early pregnancy prevents neural tube defects (NTD), but it is uncertain whether continuing FA after the first trimester has benefits on offspring health. We aimed to evaluate the effect of FA supplementation throughout pregnancy on cognitive performance and brain function in the child. METHODS: Follow-up investigation of 11-year-old children, residing in Northern Ireland, whose mothers had participated in a randomised trial of Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) in pregnancy and received 400 µg/day FA or placebo from the 14th gestational week. Cognitive performance (Full Scale Intelligence Quotient, Verbal Comprehension, Working Memory, Perceptual Reasoning, and Processing Speed) was assessed using the Wechsler Intelligence Scale for Children. Neuronal function was assessed using magnetoencephalographic (MEG) brain imaging. RESULTS: Of 119 mother-child pairs in the FASSTT trial, 68 children were assessed for neurocognitive performance at 11-year follow-up (Dec 2017 to Nov 2018). Children of mothers randomised to FA compared with placebo scored significantly higher in two Processing Speed tests, i.e. symbol search (mean difference 2.9 points, 95% CI 0.3 to 5.5, p = 0.03) and cancellation (11.3 points, 2.5 to 20.1, p = 0.04), whereas the positive effect on Verbal Comprehension was significant in girls only (6.5 points, 1.2 to 11.8, p = 0.03). MEG assessment of neuronal responses to a language task showed increased power at the Beta (13-30 Hz, p = 0.01) and High Gamma (49-70 Hz, p = 0.04) bands in children from FA-supplemented mothers, suggesting more efficient semantic processing of language. CONCLUSIONS: Continued FA supplementation in pregnancy beyond the early period currently recommended to prevent NTD can benefit neurocognitive development of the child. MEG provides a non-invasive tool in paediatric research to objectively assess functional brain activity in response to nutrition and other interventions. TRIAL REGISTRATION: ISRCTN ISRCTN19917787 . Registered on 15 May 2013.


Asunto(s)
Desarrollo Infantil , Cognición , Suplementos Dietéticos , Ácido Fólico , Efectos Tardíos de la Exposición Prenatal , Cesárea , Niño , Femenino , Ácido Fólico/uso terapéutico , Estudios de Seguimiento , Humanos , Masculino , Embarazo , Tercer Trimestre del Embarazo
13.
J Antimicrob Chemother ; 75(11): 3152-3155, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-32676634

RESUMEN

OBJECTIVES: Drug resistance of Helicobacter pylori is a major clinical problem worldwide. The objective of the present study was to investigate the prevalence of antibiotic-resistant H. pylori in the city of Shenzhen in China, as well as to identify the genetic mutations specifically associated with drug resistance rather than unrelated phylogenetic signals. METHODS: Antibiotic susceptibility testing was performed on 238 clinical strains successfully isolated from H. pylori-positive dyspeptic patients who underwent gastroscopy at the Department of Gastroenterology in Shenzhen People's Second Hospital. Following WGS of all strains using Illumina technology, mutation and phylogenetic analyses were performed. RESULTS: The resistance rates were 84.9%, 35.3%, 25.2% and 2.1% for metronidazole, clarithromycin, ciprofloxacin and rifampicin, respectively. An A2143G conversion in the 23S rRNA gene was the primary mutation observed in clarithromycin-resistant strains, whilst N87K/I and D91G/N/Y in GyrA were detected in ciprofloxacin-resistant strains. In RdxA, our results demonstrated that only R16H/C and M21A are significant contributors to metronidazole resistance; there were 15 other sites, but these are phylogenetically related and thus unrelated to metronidazole resistance. CONCLUSIONS: There is a high prevalence of metronidazole, clarithromycin and ciprofloxacin resistance and a low prevalence of rifampicin resistance in H. pylori from Shenzhen, China. Omission of phylogenetically related sites will help to improve identification of sites genuinely related to antibiotic resistance in H. pylori and, we believe, other species.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , China/epidemiología , Claritromicina/farmacología , Farmacorresistencia Bacteriana , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/genética , Humanos , Metronidazol/farmacología , Pruebas de Sensibilidad Microbiana , Mutación , Filogenia , ARN Ribosómico 23S/genética
15.
BMC Med ; 17(1): 196, 2019 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-31672132

RESUMEN

BACKGROUND: Periconceptional folic acid prevents neural tube defects (NTDs), but it is uncertain whether there are benefits for offspring neurodevelopment arising from continued maternal folic acid supplementation beyond the first trimester. We investigated the effect of folic acid supplementation during trimesters 2 and 3 of pregnancy on cognitive performance in the child. METHODS: We followed up the children of mothers who had participated in a randomized controlled trial in 2006/2007 of Folic Acid Supplementation during the Second and Third Trimesters (FASSTT) and received 400 µg/d folic acid or placebo from the 14th gestational week until the end of pregnancy. Cognitive performance of children at 7 years was evaluated using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) and at 3 years using the Bayley's Scale of Infant and Toddler Development (BSITD-III). RESULTS: From a total of 119 potential mother-child pairs, 70 children completed the assessment at age 7 years, and 39 at age 3 years. At 7 years, the children of folic acid treated mothers scored significantly higher than the placebo group in word reasoning: mean 13.3 (95% CI 12.4-14.2) versus 11.9 (95% CI 11.0-12.8); p = 0.027; at 3 years, they scored significantly higher in cognition: 10.3 (95% CI 9.3-11.3) versus 9.5 (95% CI 8.8-10.2); p = 0.040. At both time points, greater proportions of children from folic acid treated mothers compared with placebo had cognitive scores above the median values of 10 (girls and boys) for the BSITD-III, and 24.5 (girls) and 21.5 (boys) for the WPPSI-III tests. When compared with a nationally representative sample of British children at 7 years, WPPSI-III test scores were higher in children from folic acid treated mothers for verbal IQ (p < 0.001), performance IQ (p = 0.035), general language (p = 0.002), and full scale IQ (p = 0.001), whereas comparison of the placebo group with British children showed smaller differences in scores for verbal IQ (p = 0.034) and full scale IQ (p = 0.017) and no differences for performance IQ or general language. CONCLUSIONS: Continued folic acid supplementation in pregnancy beyond the early period recommended to prevent NTD may have beneficial effects on child cognitive development. Further randomized trials in pregnancy with follow-up in childhood are warranted. TRIAL REGISTRATION: ISRCTN ISRCTN19917787 . Registered 15 May 2013.


Asunto(s)
Desarrollo Infantil/efectos de los fármacos , Cognición/efectos de los fármacos , Suplementos Dietéticos , Ácido Fólico/farmacología , Niño , Preescolar , Femenino , Ácido Fólico/administración & dosificación , Estudios de Seguimiento , Edad Gestacional , Humanos , Masculino , Embarazo , Primer Trimestre del Embarazo , Segundo Trimestre del Embarazo , Tercer Trimestre del Embarazo
16.
PLoS Pathog ; 13(6): e1006464, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28644872

RESUMEN

Helicobacter pylori infection causes chronic active gastritis that after many years of infection can develop into peptic ulceration or gastric adenocarcinoma. The bacterium is highly adapted to surviving in the gastric environment and a key adaptation is the virulence factor urease. Although widely postulated, the requirement of urease expression for persistent infection has not been elucidated experimentally as conventional urease knockout mutants are incapable of colonization. To overcome this constraint, conditional H. pylori urease mutants were constructed by adapting the tetracycline inducible expression system that enabled changing the urease phenotype of the bacteria during established infection. Through tight regulation we demonstrate that urease expression is not only required for establishing initial colonization but also for maintaining chronic infection. Furthermore, successful isolation of tet-escape mutants from a late infection time point revealed the strong selective pressure on this gastric pathogen to continuously express urease in order to maintain chronic infection. In addition to mutations in the conditional gene expression system, escape mutants were found to harbor changes in other genes including the alternative RNA polymerase sigma factor, fliA, highlighting the genetic plasticity of H. pylori to adapt to a changing niche. The tet-system described here opens up opportunities to studying genes involved in the chronic stage of H. pylori infection to gain insight into bacterial mechanisms promoting immune escape and life-long infection. Furthermore, this genetic tool also allows for a new avenue of inquiry into understanding the importance of various virulence determinants in a changing biological environment when the bacterium is put under duress.


Asunto(s)
Gastritis/genética , Silenciador del Gen/fisiología , Infecciones por Helicobacter/inmunología , Helicobacter pylori/genética , Ureasa/metabolismo , Animales , Proteínas Bacterianas/metabolismo , Enfermedad Crónica , Mucosa Gástrica/microbiología , Gastritis/microbiología , Expresión Génica/genética , Ratones , Neoplasias Gástricas/genética
17.
PLoS Pathog ; 13(3): e1006280, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28306723

RESUMEN

Helicobacter pylori lipopolysaccharide promotes chronic gastric colonisation through O-antigen host mimicry and resistance to mucosal antimicrobial peptides mediated primarily by modifications of the lipid A. The structural organisation of the core and O-antigen domains of H. pylori lipopolysaccharide remains unclear, as the O-antigen attachment site has still to be identified experimentally. Here, structural investigations of lipopolysaccharides purified from two wild-type strains and the O-antigen ligase mutant revealed that the H. pylori core-oligosaccharide domain is a short conserved hexasaccharide (Glc-Gal-DD-Hep-LD-Hep-LD-Hep-KDO) decorated with the O-antigen domain encompassing a conserved trisaccharide (-DD-Hep-Fuc-GlcNAc-) and variable glucan, heptan and Lewis antigens. Furthermore, the putative heptosyltransferase HP1284 was found to be required for the transfer of the third heptose residue to the core-oligosaccharide. Interestingly, mutation of HP1284 did not affect the ligation of the O-antigen and resulted in the attachment of the O-antigen onto an incomplete core-oligosaccharide missing the third heptose and the adjoining Glc-Gal residues. Mutants deficient in either HP1284 or O-antigen ligase displayed a moderate increase in susceptibility to polymyxin B but were unable to colonise the mouse gastric mucosa. Finally, mapping mutagenesis and colonisation data of previous studies onto the redefined organisation of H. pylori lipopolysaccharide revealed that only the conserved motifs were essential for colonisation. In conclusion, H. pylori lipopolysaccharide is missing the canonical inner and outer core organisation. Instead it displays a short core and a longer O-antigen encompassing residues previously assigned as the outer core domain. The redefinition of H. pylori lipopolysaccharide domains warrants future studies to dissect the role of each domain in host-pathogen interactions. Also enzymes involved in the assembly of the conserved core structure, such as HP1284, could be attractive targets for the design of new therapeutic agents for managing persistent H. pylori infection causing peptic ulcers and gastric cancer.


Asunto(s)
Helicobacter pylori/química , Helicobacter pylori/patogenicidad , Lipopolisacáridos/química , Antígenos O/química , Animales , Western Blotting , Cromatografía de Gases , Modelos Animales de Enfermedad , Infecciones por Helicobacter/microbiología , Interacciones Huésped-Patógeno/fisiología , Ratones , Ratones Endogámicos C57BL , Resonancia Magnética Nuclear Biomolecular , Oligosacáridos/química , Dominios Proteicos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
18.
Helicobacter ; 24(1): e12544, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30324717

RESUMEN

BACKGROUND: Helicobacter pylori, gastric cancer-causing bacteria, survive in their gastric environment of more than 50% of the world population. The presence of H. pylori in the gastric vicinity promotes the development of various diseases including peptic ulcer and gastric carcinoma. H. pylori produce and secret Vacuolating cytotoxin A (VacA), a major toxin facilitating the bacteria against the host defense system. The toxin causes multiple effects in epithelial cells and immune cells, especially T cells, B cells, and Macrophages. METHODS: This review describes the diverse functionalities of protein toxin VacA. The specific objective of this review is to address the overall structure, mechanism, and functions of VacA in various cell types. The recent advancements are summarized and discussed and thus conclusion is drawn based on the overall reported evidences. RESULTS: The searched articles on H. pylori VacA were evaluated and limited up to 66 articles for this review. The articles were divided into four major categories including articles on vacA gene, VacA toxin, distinct effects of VacA toxin, and their effects on various cells. Based on these studies, the review article was prepared. CONCLUSIONS: This review describes an overview of how VacA is secreted by H. pylori and contributes to colonization and virulence in multiple ways by affecting epithelial cells, T cells, Dendritic cells, B cells, and Macrophages. The reported evidence suggests that the comprehensive outlook need to be developed for understanding distinctive functionalities of VacA.


Asunto(s)
Proteínas Bacterianas/metabolismo , Toxinas Bacterianas/metabolismo , Citotoxinas/metabolismo , Helicobacter pylori/química , Helicobacter pylori/patogenicidad , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Toxinas Bacterianas/química , Toxinas Bacterianas/genética , Citotoxinas/química , Citotoxinas/genética , Células Epiteliales , Helicobacter pylori/crecimiento & desarrollo , Humanos , Linfocitos , Macrófagos , Vacuolas/metabolismo , Virulencia
19.
J Acoust Soc Am ; 144(6): EL485, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30599659

RESUMEN

Humans have been interested in bowel sounds and wondered about their origins for millennia. To better understand the phenomenon, a mathematical model of bowel sound generation was developed based on a spring-mass-damping system. This is similar to vocal folds models for speech. The bowel sound model has four parameters that link to bowel activities: the individual wave component, pressure index, component quantity, and component interval time. All types of bowel sound documented previously can be modelled by combining different values for these parameters. Further, a 2500 ms bowel sound incorporating all the common types was simulated to present the model's accuracy.

20.
Sensors (Basel) ; 18(12)2018 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-30513934

RESUMEN

Interpretation of bowel sounds (BS) provides a convenient and non-invasive technique to aid in the diagnosis of gastrointestinal (GI) conditions. However, the approach's potential is limited by variation between BS and their irregular occurrence. A short, manual auscultation is sufficient to aid in diagnosis of only a few conditions. A longer recording has the potential to unlock additional understanding of GI physiology and clinical utility. In this paper, a low-cost and straightforward piezoelectric acoustic sensing device was designed and used for long BS recordings. The migrating motor complex (MMC) cycle was detected using this device and the sound index as the biomarker for MMC phases. This cycle of recurring motility is typically measured using expensive and invasive equipment. We also used our recordings to develop an improved categorization system for BS. Five different types of BS were extracted: the single burst, multiple bursts, continuous random sound, harmonic sound, and their combination. Their acoustic characteristics and distribution are described. The quantities of different BS during two-hour recordings varied considerably from person to person, while the proportions of different types were consistent. The sensing devices provide a useful tool for MMC detection and study of GI physiology and function.

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