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In view of a large number of people infected with Helicobacter pylori (H. pylori) with great harm followed, there is an urgent need to develop a non-invasive, easy-to-operate, and rapid detection method, and to identify effective sterilization strategies. In this study, highly specific nanoprobes with nanozyme activity, Ag@Pt nanoparticles (NPs) with the antibody, were utilized as a novel lateral flow immunoassay (LFIA). The optical label (Ag@Pt NPs) was enhanced by the introduction of the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) and compared with a gold nanoparticles (Au NPs) optical label. Under the optimal condition, Ag@Pt-LFIA and TMB-enhanced Ag@Pt-LFIA for H. pylori were successfully established, two of which were over twofold and 100-fold more sensitive than conventional visual Au NP-based LFIA, respectively. Furthermore, Ag@Pt NPs with the antibody irradiated with NIR laser (808 nm) at a power intensity of 550 mW/cm 2 for 5 min exhibited a remarkable antibacterial effect. The nanoprobes could close to bacteria through effective interactions between antibodies and bacteria, thereby benefiting photothermal sterilization. Overall, Ag@Pt NPs provide promising applications in pathogen detection and therapeutic applications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The rise in the antibiotic resistance rate of Helicobacter pylori has led to an increasing eradication failure of this carcinogenic bacterial pathogen worldwide. This underlines the need for alternative antibacterial strategies against H. pylori infection. Antimicrobial photodynamic therapy (aPDT) is a promising non-pharmacological antibacterial technology. In this study, the selective killing activities of three benzylidene cyclopentanone (BCP) photosensitizers (Y1, P1 and P3) towards H. pylori over normal human gastric epithelial GES-1 cells were evaluated and the ex vivo photodynamic inactivation effect was preliminarily assessed on twelve H. Pylor-infected mice. Results showed that under the irradiation of 24 J/cm 2 532 nm laser, Y1, P1 and P3 at 2.5 μM induced a 3-log 10 reduction of H. pylori CFU (99.9% killing). Confocal images showed that P3, unlike Y1 and P1, could not be uptaken by GES-1 cells. P3 at 2.5 to 20 μM showed not significant (p > 0.05) phototoxicity to GES-1 cells, nevertheless, Y1 and P1 under the same concentrations exhibited remarkable phototoxicity to GES-1 cells. In the co-culture of H. pylori and GES-1 cells, P3 at 2.5 μM led to a complete eradication of H. pylori under the irradiation of 24 J/cm 2 532 nm laser. While for the GES-1 cells, no significant (p > 0.05) phototoxicity was observed under the same aPDT dosage. The ex vivo experiments showed that P3 mediated aPDT resulted in 82.4% to 100% reduction of H. pylori CFU without damaging the gastric mucosa. To sum up, P3 is a promising anti-H. pylori photosensitizer with the ability to selectively photo-inactivate H. pylori while sparing normal gastric tissues., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction. Growing concern about the increasing frequency of resistance of Helicobacter pylori to the available antimicrobial agents worldwide has encouraged the search for new strategies in treating and eradicating H. pylori infections. Endoscopic blue-light therapy has been used in patients with H. pylori gastritis with limited success due to subsequent repopulation with H. pylori . Clinical trials using Curcumin could not eradicate infection either. Aim. We studied the effect of blue light emitting diodes (LEDs) in conjunction with Curcumin on H. pylori , since this has not been previously reported. Methodology. We examined the effect of Curcumin with and without irradiation with blue LEDs on the viability of H. pylori and four key factors important for colonization and establishment of H. pylori infection, namely urease production, motility, adhesion and biofilm formation. Results. We found that a combination of Curcumin and blue LEDs caused significant reductions in viability, urease production, motility, haemagglutination activity, as well as increased disruption of mature preformed biofilms of H. pylori , in comparison to Curcumin alone ( P <0.0001), at sublethal concentrations of Curcumin. Conclusion. Targeting the virulence factors of H. pylori with blue LED photoactivated Curcumin would theoretically cripple this pathogen from colonizing and causing tissue damage and perhaps overcome the problem of repopulation with H. pylori that often occurs following endoscopic blue-light therapy.

Background: The endogenous photosensitizing porphyrins in Helicobacter pylori (H. pylori), make blue light therapy an attractive addition to the armamentarium in the war against this very prevalent and difficult to treat infectious agent., Methods: In the current study we examined in vitro the effect of blue LED (Light Emitting Diode) irradiation for 1-6 minutes on the viability and virulence factors of H. pylori, which allow this microorganism to colonize and establish infection. Specifically, we examined the effects of blue LED on urease production, motility, adhesion and biofilm formation., Results: We found that exposure to blue LED for 1-6 minutes significantly decreased the viability of H. pylori and caused decreased urease activity, as well as, swarming motility. Furthermore, blue LED irradiation for 6 minutes caused greater than 50% disruption of preformed mature biofilms of H. pylori, relative to controls., Conclusions: Collectively, the results of our in-vitro study indicate that therapy with blue LED may be an added weapon in the eradication of H. pylori by targeting the virulence factors of this very common pathogen. We envisage that phototherapy will have an adjuvant effect on conventional anti-H. pylori therapy, especially considering its efficacy in biofilm disruption and the fact that microorganisms are unlikely to develop resistance as a result of the multi-target effects.

Since many years it has been acknowledged that some bacterial species, among which H. pylori, P. aeruginosa, P. acnes accumulate endogenous photosensitizers (PS) in the form of porphyrins. This makes antibacterial photodynamic therapy (PDT) easier to perform due to the possible avoidance of external PS. In this study, we focus on gastric infections associated with the presence of Helicobacter pylori (H. pylori), known to accumulate and release both protoporphyrin IX (PPIX) and coproporphyrins. PDT versus H. pylori can be carried out by modified endoscopes or by new ingestible luminous devices under development. In both cases of in vitro and in vivo applications, either for therapy (PDT) or diagnosis, scientific literature lacks studies on the possible side-effects of light treatments on the surrounding tissues. To this aim we evaluated in vitro side-effects due to a possible intrinsic photosensitivity of gastric mucosa or to a photosensitization by the PS released from the bacterium itself. Photo-toxicity studies were conducted on the AGS cell line (ATCC® CRL-1739™), commonly used as a model for the stomach mucosa tissue, considering PPIX as the photosensitizing agent. After first evaluations of PPIX dark toxicity, its uptake and accumulation sites, photo-toxicity tests were conducted using a LED light source peaked at 400 nm, by varying both PPIX concentration (50 nM - 2 μM) and light dose in the range 0.6-13 J/cm 2 , representing different treatment procedures found in literature. The oxidative stress consequent to irradiation was investigated both in terms of ROS production and assessment of the activity of enzymes involved in ROS-related biological mechanisms. A significant phototoxic effect was found only for PPIX concentration > 100 nM for all tested light doses. This indicates that the evaluated photo-treatments do not cause side effects even with the sensitization due to PPIX released by the bacteria., (Copyright © 2018. Published by Elsevier B.V.)

Background and Aim: Infection by Helicobacter pylori is implicated in a wide range of upper gastrointestinal diseases. Owing to the rapid emergence of antibiotic-resistant strains of H. pylori, the development of novel treatment modalities for antibiotic-resistant H. pylori infection is a key priority. Blue light-emitting diodes (LED) may represent a unique option owing to their antimicrobial effect. In this study, we aimed to evaluate the anti-proliferative effect of blue LED against antibiotic-resistant H. pylori., Methods: Ten antibiotic-resistant strains and one sensitive H. pylori strain were used in this study. After irradiation by blue LED along time course, the viability of H. pylori was evaluated by enumerating colony forming units. Morphological changes in H. pylori were observed using a scanning electron microscope. Reductase activity was measured as an indicator of bacterial cellular activity. Total reactive oxygen species was monitored using fluorescence intensity and fluorescence microscope imaging., Results: After irradiation by blue LED, the numbers of H. pylori in all the strains were significantly reduced compared with control group. The H. pylori exhibited a short rod-shaped morphology after irradiation; no such change was observed in H. pylori not exposed to blue LED. Re-irradiation of surviving strain after the initial irradiation also exhibited the same anti-proliferation effect. After blue LED irradiation, bacterial cellular activity was lower, and total reactive oxygen species production was significantly higher in blue LED group, compared with that in control., Conclusions: Blue LED could be a new treatment to eradicate infection with antibiotic-resistant H. pylori., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Gastrointestinal endoscopy is an important tool for the indentification and treatment of disorders of the gastrointestinal tract. However, nosocomial infections of Helicobacter pylori have been linked to the use of contaminated endoscopes. Disinfectants such as glutaraldehyde, ortho-phthalaldehyde and peracetic acid are generally used in the reprocesssing of endoscopes, but these chemicals are hazardous to human health. Thus, safer reprocessing and disinfecion methods are needed. In this study, we applied a dielectric barrier discharge (DBD) plasma torch for inactivation of H. pylori to investigate a potential new methodology to disinfect endoscopes. Suspensions of H. pylori in 10% glycerol were subjected to the DBD plasma torch, which reduced the viable cell count to undetectable levels after 2 min of treatment. Furthermore, urease activity of H. pylori was eliminated after 2 min-plasma treatment, while plasma-treatment reduced the intact DNA of H. pylori in a time-dependent manner. Next, we examined several potential bactericidal factors produced by the DBD plasma torch. Two min-plasma treatment resulted in a small temperature rise (4 °C), ultraviolet radiation (UV) generation, and the production of hydrogen peroxide. H. pylori samples were then exposed to equivalent levels of each of these factors in turn. Our results showed that treatment with heat and hydrogen peroxide at the levels produced after 2-min of plasma treatment did not efficiently inactivate H. pylori, whereas exposure to UV had a significant bactericidal effect. Taken together, UV generated by the plasma torch may be crucial for efficient inactivation of H. pylori by damaging the bacterial DNA., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To investigate the eradicate effect of Helicobacter pylori in differentiated thyroid cancer patients who underwent I therapy., Materials and Methods: A total of 130 patients with differentiated thyroid cancer underwent I treatment. None of the patients had a history of stomach-related diseases. The C-urea breath test (UBT) was carried out for H. pylori examination before I treatment. The cut-off value for C-UBT was 4%. For H. pylori test-positive patients, a second C-UBT was performed 4-6 weeks after I treatment. T-tests were used to compare the difference before and 4-6 weeks after I treatment., Results: A total of 42 of 130 (32.31%) patients were H. pylori positive. The average value of H. pylori was 28.36% before I, whereas the value was 18.18% after I therapy. A significant decrease in C-UBT was found after I treatment compared with before therapy (P<0.01)., Conclusion: Our preliminary data showed that I exerts certain eradication effects on H. pylori, which could provide a new approach to multidrug resistance pathogens. As the exact molecular mechanism of this phenomenon is still unclear, future clinical applications of this anecdotal finding require further assessments.

A photo-medical capsule that emits blue light for Helicobacter pylori treatment was described in this paper. The system consists of modules for pH sensing and measuring, light-emitting diode driver circuit, radio communication and microcontroller, and power management. The system can differentiate locations by monitoring the pH values of the gastrointestinal tract, and turn on and off the blue light according to the preset range of pH values. Our experimental tests show that the capsule can operate in the effective light therapy mode for more than 32 minutes and the wireless communication module can reliably transmit the measured pH value to a receiver located outside the body.

Background: Photodynamic therapy (PDT) is a method for killing cells (bacterial, fungal and cancer cells) or virus using photosensitizers (PS) and light of various wavelengths. In vitro PDT using endoscopic light against H. pylori was effective at a concentration of 0.2mg/mL of MB. The purpose of this study was to increase the effect of photodynamic modality against H. pylori by addition of chitosan to MB., Methods: The bactericidal effect was measured by counting viable cells after PDT. The degree of damage to DNA was confirmed using alkaline gel electrophoresis. Cellular DNA damage was demonstrated by ethidium bromide monoazide-quantitative polymerase chain reaction (EMA-qPCR)., Results: In the groups treated with either 0.04 mg/mL MB alone or 0.02 mg/mL MB with endoscopic light for 15 min, viable cells were decreased approximately tenfold. The group treated with 0.04 mg/mL of MB with light, showed more effective bactericidal activity than 0.02 mg/mL of MB treatment. By 0.05% chitosan pre-treatment followed with 0.04 mg/mL of MB and light irradiation, viable cells were decreased 10(7)-fold. The DNA damage caused by PDT as demonstrated by alkaline gel electrophoresis was greater in the MB plus chitosan-treated group than in control and MB-treated groups. Cellular DNA damage demonstrated by EMA-qPCR was also greater in the group treated with MB plus chitosan than in the MB-treated group., Conclusion: The bactericidal effects with PDT using MB were increased with the concentration of photosensitizer and chitosan treatment, peculiarly before endoscopic light irradiation., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Helicobacter pylori (HP) infections are considered to be the main cause for chronic gastritis and gastric ulcers, whereby more than half of the world's population is nowadays infected. The increased use of antibiotics is leading to an enhanced resistance. Photodynamic inactivation of bacteria seems to be a potential alternative for antibiotic therapies. In our study we used the photosensitizer Chlorin e6 (Ce6) in combination with red light-emitting diodes to inactivate HP in vitro. Ce6 uptake is determined by spectroscopy. Furthermore diverse experiments of different concentrations in the range of 0-100 μM of the photosensitizer and exposure times up to 300 s are carried out in order to find optimal irradiation parameters (wavelength: 660 nm, power density: 9 mW/cm(2), absorbed dose: up to 2.7 J/cm(2)). The data show a significant reduction after already a few seconds of illumination, even with a low Ce6 concentration in the sub-μM-region. At a concentration of 100 μM a nearly total inactivation (6-log10-reduction) of HP was achieved within 60s of irradiation., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Purpose: Radioactive Iodine therapy (RAIT) plays a major role in the treatment of hyperthyroidism. In addition to the thyroid gland, significant amounts of radioactive iodine are maintained in the stomach. The aim of this study was to determine if RAIT has any effect on Helicobacter pylori infection, based on the C urea breath test (UBT)., Materials and Methods: The study included 85 patients with hyperthyroidism scheduled to undergo RAIT and 69 hyperthyroid subjects in whom methimazole treatment was planned. All subjects had pretreatment-positive UBT results, and the test was repeated on the first and third months after RAIT and methimazole treatment., Results: After a mean RAIT dose of 15 mCi (range, 10-20 mCi), UBT became negative in 13 (15.3%) of 85 patients on the first month and 18 (21.2%) of 85 patients on the third month. All subjects treated with methimazole remained UBT positive on the first and third months of methimazole treatment (100%). Reduction in the number of UBT-positive patients on both the first and the third months after RAIT was statistically significant (P < 0.001). Distribution of hyperthyroidism etiologies and thyroid autoantibody levels in subjects with UBT that became negative and in subjects with UBT that remained positive were similar in the RAIT group (P > 0.05). Urea breath test negativity rates did not differ according to the radioiodine dose., Conclusions: Our findings indirectly showed that RAIT might have an antimicrobial effect on H. pylori. Clinical applications of this beneficial effect of RAIT on H. pylori should be further evaluated.

We investigated whether near-ultraviolet light emitted from light-emitting diodes (LEDs) effects Helicobacter pylori viability and whether this new method can potentially apply to eradication therapy. Three H. pylori strains were used for near-ultraviolet (UV) LED irradiation experiments. Viability of isolates exposed to near-UV light was compared with controls by counting colony forming units. A time-dependent bactericidal effect of near-UV light was definitely observed. LED irradiation with near-UV light showed effective bactericidal activity against H. pylori strains. Eradication therapy with LED might provide a new avenue of treatment in patients refractory to eradication due to antibiotic resistance and/or adverse effects of antibiotics.

About half of the world's population is currently infected with Helicobacter pylori, which is involved in the development of several gastro-duodenal pathologies. The increasing number of antibiotic resistance reduces the effectiveness of the first-line therapy, so new strategies to improve the H. pylori eradication rates are needed. Antimicrobial Photodynamic Therapy (APDT) benefits from photogenerated reactive oxygen species, such as singlet oxygen, which inactivate microorganisms by means of photosensitising dyes and visible light. Therefore, it could be a suitable alternative for H. pylori eradication in the gastro-duodenal tract, particularly in patients infected with antibiotic resistant strains. We evaluated APDT against H. pylori, in vitro, using a new photosensitising material (PSM) based on a ruthenium(II) complex covalently bound to micrometric glass beads. Five H. pylori isolates (classified according to cagA genotype, and metronidazole-clarithromycin resistance) were used. Bacteria were mixed with the PSM and incubated in the dark or illuminated by blue light. Aliquots (min 1', 2', 5', 15' and 30') were cultured and colonies were counted after 2-3 days. A 99.99999% decrease was detected in the number of colonies in the irradiated wells where the bacterium was mixed with the PSM, compared to non-illuminated wells or with irradiated wells without PSM. It was also confirmed that DNA is a molecular target for oxidant species released during APDT (evaluated by alkaline gel electrophoresis after endonuclease III incubation, ureC and cagA RT-PCR, and bacterial fingerprint). Results were independent of cagA gene and antibiotic resistances., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Helicobacter pylori might be readily affected with photodynamic therapy (PDT) by weak wavelengths, because it has few repair genes. Recently, gastrointestinal endoscopy emitting specific wavelengths (narrowband imaging, NBI) has been developed for the early detection of tumors. Coincidentally, its wavelength (415 nm) is very similar to the wavelength (410 nm) that activates protoporphyrin IX (PpIX) as a photosensitizer (PS). Therefore, we studied in vitro PDT against H. pylori using NBI and conventional white light (WL) according to low or high concentration of PpIX along with exposure time. The bactericidal effects, the degree of oxidative DNA damage and membrane integrity of H. pylori after PDT were evaluated. In the control, the numbers of viable cells remained constant during the experiment. Viable cells after PDT using both endoscopic light irradiation, were decreased approximately 10(3) - 10(5) fold at low concentration of PpIX and below 0.80 × 10 at high concentration of PpIX. Only membrane damage after PDT was observed microscopically in H. pylori without DNA injury. Conclusively, either the bactericidal effect in high concentration or the decrease of bacterial loading in low concentration of PpIX, would be expected with PDT using endoscopic light (NBI or WL)., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Blue light, particularly in the wavelength range of 405-470 nm, has attracted increasing attention due to its intrinsic antimicrobial effect without the addition of exogenous photosensitizers. In addition, it is commonly accepted that blue light is much less detrimental to mammalian cells than ultraviolet irradiation, which is another light-based antimicrobial approach being investigated. In this review, we discussed the blue light sensing systems in microbial cells, antimicrobial efficacy of blue light, the mechanism of antimicrobial effect of blue light, the effects of blue light on mammalian cells, and the effects of blue light on wound healing. It has been reported that blue light can regulate multi-cellular behavior involving cell-to-cell communication via blue light receptors in bacteria, and inhibit biofilm formation and subsequently potentiate light inactivation. At higher radiant exposures, blue light exhibits a broad-spectrum antimicrobial effect against both Gram-positive and Gram-negative bacteria. Blue light therapy is a clinically accepted approach for Propionibacterium acnes infections. Clinical trials have also been conducted to investigate the use of blue light for Helicobacter pylori stomach infections and have shown promising results. Studies on blue light inactivation of important wound pathogenic bacteria, including Staphylococcus aureus and Pseudomonas aeruginosa have also been reported. The mechanism of blue light inactivation of P. acnes, H. pylori, and some oral bacteria is proved to be the photo-excitation of intracellular porphyrins and the subsequent production of cytotoxic reactive oxygen species. Although it may be the case that the mechanism of blue light inactivation of wound pathogens (e.g., S. aureus, P. aeruginosa) is the same as that of P. acnes, this hypothesis has not been rigorously tested. Limited and discordant results have been reported regarding the effects of blue light on mammalian cells and wound healing. Under certain wavelengths and radiant exposures, blue light may cause cell dysfunction by the photo-excitation of blue light sensitizing chromophores, including flavins and cytochromes, within mitochondria or/and peroxisomes. Further studies should be performed to optimize the optical parameters (e.g., wavelength, radiant exposure) to ensure effective and safe blue light therapies for infectious disease. In addition, studies are also needed to verify the lack of development of microbial resistance to blue light., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

For naturally competent microorganisms, such as Helicobacter pylori, the steps that permit recombination of exogenous DNA are not fully understood. Immediately downstream of an H. pylori gene (dprA) that facilitates high-frequency natural transformation is HP0334 (dprB), annotated to be a putative Holliday junction resolvase (HJR). We showed that the HP0334 (dprB) gene product facilitates high-frequency natural transformation. We determined the physiologic roles of DprB by genetic analyses. DprB controls in vitro growth, survival after exposure to UV or fluoroquinolones, and intragenomic recombination. dprB ruvC double deletion dramatically decreases both homologous and homeologous transformation and survival after exposure to DNA-damaging agents. Moreover, the DprB protein binds to synthetic Holliday junction structures rather than double-stranded or single-stranded DNA. These results demonstrate that the dprB product plays important roles affecting inter- and intragenomic recombination. We provide evidence that the two putative H. pylori HJRs (DprB and RuvC) have overlapping but distinct functions involving intergenomic (primarily DprB) and intragenomic (primarily RuvC) recombination.

Helicobacter pylori is a bacterial pathogen colonizing half of the world's human population. It has been implicated in a number of gastric diseases, from asymptomatic gastritis to cancer. It is characterized by an amazing genetic variability that results from high mutation rates and efficient DNA homologous recombination and transformation systems. Here, we report the characterization of H. pylori RecA (HpRecA), a protein shown to be involved in DNA repair, transformation, and mouse colonization. The biochemical characterization of the purified recombinase reveals activities similar to those of Escherichia coli RecA (EcRecA). We show that in H. pylori, HpRecA is present in about 80,000 copies per cell during exponential growth and decreases to about 50,000 copies in stationary phase. The amount of HpRecA remains unchanged after induction of DNA lesions, suggesting that HpRecA is always expressed at a high level in order to repair DNA damage or facilitate recombination. We performed HpRecA localization analysis by adding a Flag tag to the protein, revealing two different patterns of localization. During exponential growth, RecA-Flag presents a diffuse pattern, overlapping with the DAPI (4',6-diamidino-2-phenylindole) staining of DNA, whereas during stationary phase, the protein is present in more defined areas devoid of DAPI staining. These localizations are not affected by inactivation of competence or DNA recombination genes. Neither UV irradiation nor gamma irradiation modified HpRecA localization, suggesting the existence of a constitutive DNA damage adaptation system.

Unlabelled: 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.

Photodynamic therapy (PDT) is a method for inactivating cells (viral, bacterial and cancer cells) using photosensitizers (PS) and light of various wavelengths. Helicobacter pylori might be easily affected by light because it has few genes to repair light-induced DNA damage. In vitro PDT against H. pylori was conducted using endoscopic white light and methylene blue (MB) as the PS before application to in vivo study. The bactericidal effects were measured by counting viable cells after PDT. The degree of oxidative damage of DNA was confirmed using alkaline gel electrophoresis, real-time PCR (RT-PCR) and an assay of 8-hydroxy-2-deoxyguanosine (8-OHdG). In the control group, the number of viable cells was maintained constantly during the experiment. In the groups treated with either 0.2mg/mlMB alone or white light with 0.02mg/mlMB for 10min, bacteria decreased approximately a hundredfold. The killing effect increased proportionally to the PS concentration and the duration of irradiation. DNA damage by PDT proven by alkaline gel electrophoresis, RT-PCR and assay of 8-OHdG, was greater in PDT-treated groups than in control. PDT using MB and endoscopic white light showed effective bactericidal activity in vitro by oxidative DNA damage of H. pylori., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The aim of this work was to investigate the effects of exposure to extremely low-frequency electromagnetic fields (ELF-EMF) both on biofilm formation and on mature biofilm of Helicobacter pylori. Bacterial cultures and 2-day-old biofilm of H. pylori ATCC 43629 were exposed to ELF-EMF (50 Hz frequency-1 mT intensity) for 2 days to assess their effect on the cell adhesion and on the mature biofilm detachment, respectively. All the exposed cultures and the respective sham exposed controls were studied for: the cell viability status, the cell morphological analysis, the biofilm mass measurement, the genotypic profile, and the luxS and amiA gene expression. The ELF-EMF acted on the bacterial population during the biofilm formation displaying significant differences in cell viability, as well as, in morphotypes measured by the prevalence of spiral forms (58.41%) in respect to the controls (33.14%), whereas, on mature biofilm, no significant differences were found when compared to the controls. The measurement of biofilm cell mass was significantly reduced in exposed cultures in both examined experimental conditions. No changes in DNA patterns were recorded, whereas a modulation in amiA gene expression was detected. An exposure to ELF-EMF of H. pylori biofilm induces phenotypic changes on adhering bacteria and decreases the cell adhesion unbalancing the bacterial population therefore reducing the H. pylori capability to protect itself.

Comparative analysis of results of surgical treatment, performed for perforative gastroduodenal ulcers in the patients, lacking H. pylori (control group) and owing this etiologic factor (main group), was conducted. Together with other conventional schemes of medicinal treatment in the early postoperative period a low-intensive irradiation of He-Ne laser was applied. Complete eradication of H. pylori was noted in 95.8% patients of the main group. In a late follow-up period (in 1-5 yrs observation terms) the frequency of recurrence, hemorrhage, pyloroduodenal stenosis and other surgical complications, occurring in the main group, was lesser than in a control one.

Background: Helicobacter pylori is the most important cause of gastritis and related morbidities. Following consumption, radioactive iodine accumulates considerably in the stomach. On the basis of this observation, we decided to determine whether the high radiation induced by radio-iodine in the stomach is effective in the eradication of this infection., Methods: All consecutive patients with differentiated thyroid carcinoma, who were referred for radio-iodine therapy [dose 117.1 +/- 24.4 mCi (4.3 +/- 0.9 GBq), range 100-200 mCi (3.7-7.4 GBq)], were enrolled. To detect H. pylori infection, the urease breath test (UBT) was performed 1-2 h before radio-iodine consumption and the test was repeated 2 months later., Results: Of 88 patients, 71 had pre-treatment positive UBT. Of these, 23 patients had negative post-treatment result, which means a significant reduction (26.1%, 95% CI 16.8-35.5%) in the number of positive UBT results in our treated population (32.4% of UBT-positive cases became UBT-negative)., Conclusions: Considering the high prevalence of reinfection in developing countries, the therapeutic benefit would have been more considerable if the second UBT had been done with a lag time of less than 2 months. Although radio-iodine therapy is not a logical method for the treatment of patients suffering from H. pylori, our finding provides indirect evidence about the radiosensitivity of bacteria, the future clinical applications of which need to be further evaluated. Also this finding can be useful for the food industry, where radiation is used widely to sterilize food. Regarding the possibility of H. pylori suppression, we recommend not using UBT for screening for the infection for at least within 2 months following radio-iodine therapy.

The most common low-grade non-Hodgkin lymphomas are of B-cell origin. This review will focus on follicular lymphomas and extranodal marginal zone lymphomas, also known as mucosa-associated lymphoid tissue (MALT) lymphomas. These are radiation-sensitive lymphomas. Moderate doses (30-35 Gy) for these stage I and II low-grade lymphomas result in long-term local control and possible cure. Involved-field radiation therapy is the standard approach and produces minimal morbidity. However, a significant proportion of patients relapse with systemic disease outside of radiation fields. For follicular lymphoma, this occurs in approximately 50% of patients after 15 years and for nongastric MALT lymphoma 30% to 40% after 10 years. Patients with relapsed disease are not curable with chemotherapy, but the disease often remains indolent and prolonged survival is observed. For gastric MALT lymphomas associated with Helicobacter pylori but which did not respond to antibiotic therapy, radiation treatment is indicated and almost always curative. For localized MALT lymphomas not related to microorganisms, radiation therapy is the initial standard therapy regardless of anatomic location. Patients with stage III and IV low-grade lymphoma and local symptoms are often successfully palliated with a low dose regimen of 2 x 2 Gy (total dose 4 Gy).

Helicobacter pylori has a highly variable genome with ongoing diversification via inter- and intragenomic recombination and spontaneous mutation. DNA repair genes modulating mutation and recombination rates that influence diversification have not been well characterized for H. pylori. To examine the role of putative base excision repair ung and mutY glycosylase and xthA apurinic/apyrimidinic endonuclease genes in H. pylori, mutants of each were constructed in strain JP26 by allelic exchange. Spontaneous mutation frequencies of JP26 mutY mutants, assessed by rifampin resistance, were consistently higher (26-fold) than that of the wild type, whereas the ung and xthA mutants showed smaller increases. In trans complementation of the JP26 mutY mutant restored spontaneous mutation frequencies to wild-type levels. In cross-species studies, H. pylori mutY complemented an Escherichia coli mutY mutant and vice versa. In contrast, the ung and mutY mutants did not show higher frequencies of intergenomic recombination or greater sensitivity to UV-induced DNA damage than the wild type. The H. pylori mutY open reading frame contains an eight-adenine homonucleotide tract; we provide evidence that this is subject to slipped-strand mispairing, leading to frameshifts that eliminate gene function. Our findings indicate that H. pylori possesses phase-variable base excision repair, consistent with a tension between repair and mutation.

Although it has been suggested that cardiovascular disease incidence is increased among atomic bomb survivors, the existence of a causal relationship between radiation exposure and atherosclerosis is unclear. Microbial infections, including those caused by Chlamydia pneumoniae, Helicobacter pylori and cytomegalovirus, have recently been implicated in atherosclerosis. Since immune function is somewhat impaired among atomic bomb survivors, their immune defense against such infections might be diminished. To investigate this possibility, we measured antibody levels to the above microorganisms in the sera of survivors. We found that the levels of IgG and IgA antibodies to Chlamydia pneumoniae decreased significantly with radiation dose, whereas the levels of IgG antibodies to Helicobacter pylori or cytomegalovirus remained unchanged. The inflammation marker C-reactive protein was significantly and positively associated with level of antibodies to Chlamydia pneumoniae only in heavily exposed (>or=1000 mGy) survivors. These results may suggest that among atomic bomb survivors, immune response to Chlamydia pneumoniae is diminished and chronic inflammatory reactions related to Chlamydia pneumoniae infection are present.

Three strains of Helicobacter pylori were exposed to UV light from a low-pressure source to determine log inactivation versus applied fluence. Results indicate that H. pylori is readily inactivated at UV fluences typically used in water treatment regimens. Greater than 4-log(10) inactivation was demonstrated on all three strains at fluences of less than 8 mJ cm(-2).

Helicobacter pylori colonizes the mucus layer of the human stomach and duodenum, causes chronic gastritis, gastric ulcer, and is a risk factor for gastric adenocarcinoma. There is a 20% failure rate in antibiotic therapy, which is increasingly due to antibiotic resistance and necessitates the search for alternative antimicrobial methods. We have discovered that H. pylori when cultured in liquid medium, accumulates significant quantities of coproporphyrin and protoporphyrin IX, both in the cells and secreted into the medium. These photoactive porphyrins lead to cell death (up to 5 logs) by photodynamic action upon illumination with low doses of visible light, with blue/violet light being most efficient. The degree of killing increases with the age of the culture and is greater than that found with Propionibacterium acnes (another bacterium known to be photosensitive due to porphyrin accumulation). Both virulent and drug-resistant strains are killed. The data suggest that phototherapy might be used to treat H. pylori infection in the human stomach.

Background: Helicobacter pylori colonizes the mucus layer of the human stomach and may cause peptic ulcer and adenocarcinoma. Novel antimicrobial approaches are sought due to the occurrence of antibiotic resistance and consequent treatment failure. We report here that H. pylori is susceptible to inactivation by blue light., Study Design/materials and Methods: A controlled, prospective, blinded, trial of endoscopically delivered blue light to eradicate H. pylori in regions of the gastric antrum, in 10 patients between the ages of 21 and 80 who tested positive for H. pylori. Light (405 nm) (40 J/cm2) was delivered to a 1-cm diameter spot in the gastric antrum via optical fiber passed through the endoscope and weighed biopsies were taken from treated and control spots and colonies quantitatively cultured., Results: Blue light killed 5 logs of bacteria in vitro. The mean reduction in H. pylori colonies per gram tissue between treated and control spots was 91% (7.4+/-4.8 x 10(6) vs. 8.1+/-1.9 x 10(7), two-tailed P < 0.0001). Some patients had reductions approaching 99%. No differences were observed on histological examination of light-treated and control gastric tissue., Conclusion: Blue light phototherapy may represent a novel approach to eradication of H. pylori, particularly, in patients who have failed standard antibiotic treatment., (Copyright 2005 Wiley-Liss, Inc.)

Laser iridotherapy was carried out simultaneously with irradiation of immuno-competent zones on the integument of the human body in patients with stomach and duodenal ulcers. As a result of such treatment, it was discovered that laser therapy has immunomodulating action leading to the reduction of the ulcer cicatrisation period.

The aim of our investigation was to study the influence of low-intensity laser therapy at the immunologic parameters and Helicobacter pylori (HP) microbial contamination in patients with exacerbation of peptic and duodenal ulcer. 100 patients aged 18-65 were examined and divided into 2 groups. The experimental group (75 patients) underwent a complex drug and laser therapy of various therapeutic techniques. The control group (25 patients) underwent only drug therapy. The results of this study show the immunocorrective effect of different methods of low-intensity laser therapy in the exacerbation period and more essential decrease of HP microbial contamination in the experimental group.

Background and Objectives: Helicobacter pylori (HP) is an endemic pathogenic bacterium causing gastritis and gastroduodenal ulceration in humans and is linked to the development of gastric malignancies. These first human in vivo studies investigated the photoeradication of HP using laser and white light., Study Design/materials and Methods: In 13 HP-positive volunteers, a zone of gastric antrum was irradiated with laser (410 nm, 50 J/cm(2)) or endoscopic white light (10 J/cm(2)) 45 minutes after oral 5-aminolevulinic acid (5-ALA) 20 mg/kg. HP-eradication was assessed by biopsy urease test and HP-culture from irradiated and control zones 5 minutes, 4 and 48 hours post-irradiation., Results: A maximum eradication effect was achieved at 4 hours post-irradiation when 85% of biopsies in the monochromatic and 66% in the white light exposed zones, and 58 and 33% in the respective control zones were HP-negative., Conclusions: HP numbers were greatly reduced following exposure to 5-ALA and either laser or white light in vivo. Photoeradication appears feasible, but further light dosimetry and the development of convenient application methods is required., (Copyright 2002 Wiley-Liss, Inc.)

Helicobacter pylori persists in the human stomach where it may encounter a variety of DNA-damaging conditions, including gastric acidity. To determine whether the nucleotide excision repair (NER) pathway contributes to the repair of acid-induced DNA damage, we have cloned the putative H. pylori NER gene, uvrB. Degenerate oligonucleotide primers based on conserved amino acid residues of bacterial UvrB proteins were used in PCR with genomic DNA from H. pylori strain 84-183, and the 1.3-kb PCR product from this reaction was used as a probe to clone uvrB from an H. pylori genomic library. This plasmid clone had a 5.5-kb insert containing a 2.0-kb ORF whose predicted product (658 amino acids; 75.9 kDa) exhibited 69.5% similarity to E. coli UvrB. We constructed an isogenic H. pylori uvrB mutant by inserting a kanamycin-resistance cassette into uvrB and verified its proper placement by Southern hybridization. As with uvrB mutants of other bacteria, the H. pylori uvrB mutant showed a greatly increased sensitivity to the DNA-damaging agents methylmethane sulfonate and ultraviolet radiation. The uvrB mutant also was significantly more sensitive than the wild-type strain to killing by low pH, suggesting that the H. pylori nucleotide excision repair (NER) pathway is involved in the repair of acid-induced DNA damage.

Helicobacter pylori is associated with various gastrointestinal disorders. Lethal photosensitisation was investigated as a possible technique for killing H. pylori which might offer a better alternative to antibiotics. The susceptibility of H. pylori to lethal photosensitisation was determined by mixing suspensions of H. pylori with various photosensitisers and plating out on blood agar before irradiation with low-power laser light. Five sensitisers were studied further by mixing them with H. pylori in a tissue-culture plate and counting survivors after irradiation as a function of laser exposure time, dye concentration and pre-irradiation time. Crystal violet and thionine were ineffective as sensitisers, but zones of inhibition appeared with methylene blue (MB), protoporphyrin IX (PPIX), haematoporphyrin derivative (HPD), toluidine blue O (TBO) and disulphonated aluminium phthalocyanine (S2). Laser light or sensitiser alone did not affect bacterial viability. S2 (100 microg/ml) with a laser light energy density of 16 J/cm2, HPD (10O microg/ml) with 160 J/cm2, MB (100 microg/ml) with 21 J/cm2, PPIX (150 microg/ml) with 320 J/cm2 and TBO (50 microg/ml) with 160 J/cm2 all reduced bacterial viability by >99%. The killing of sensitised H. pylori by laser light offers a new approach to the treatment of localised infections when all colonised areas are accessible to light.

Results are presented of treatment of 109 patients with prolonged nonhealing gastric ulcers using a new method of highly intensive impulse laser radiation. A scarring effect was achieved in 87% of cases. Correction of immunological indices and sanation of pathological flora, apparently, contributes to the favourable effect.