Search Results (46)

Helicobacter pylori (H. pylori) is regarded as a significant risk factor for gastritis, peptic ulcer disease, and gastric cancer. However, the increasing resistance of H. pylori strains has resulted in low eradication rates and ineffective treatments. Herein, we report on identification of a new quipazine derivative—compound 9c (N-(3-chlorobenzyl)-2-(piperazin-1-yl)quinolin-4-amine), which displayed antibacterial properties (MIC range 2–4 µg/mL) against H. pylori CagA-positive reference strains associated with an increased risk of gastric cancer, including metronidazole-resistant ATCC 43504, clarithromycin-resistant ATCC 700684 and susceptible J99 strain, as well as clinical, multidrug-resistant isolate (3CML, resistant to clarithromycin, metronidazole and levofloxacin). Compound 9c showed bacteriostatic activity (MBC/MIC ratio > 4), demonstrated antibiofilm-forming properties and prevented auto-aggregation of microbial cells. It also displayed an additive effect in ½ MIC (2 µg/mL) when administered with clarithromycin and/or metronidazole. Compound 9c had no impact on gut microbiota reference strains of S. aureus, E. coli, E. faecalis and L. paracasei as well as no hemolytic activity against sheep erythrocytes. Finally, by reducing the viability of the SNU-1 human gastric cancer cell line (IC₅₀ = 3.28 μg/mL), compound 9c might offer important implications regarding the oncogenic characteristics of cagA+ H. pylori strains. Full article

Helicobacter pylori is a Gram-negative bacterium that infects almost half of the global population and is linked to gastric conditions like peptic ulcers and gastric cancer, as well as other diseases such as neurological disorders, cardiovascular problems, and iron deficiency anemia. Its survival in the acidic stomach environment is due to virulence factors like urease, flagella, and adhesion proteins (BabA, SabA). Current treatments involve a combination of antibiotics (clarithromycin, metronidazole, amoxicillin, tetracycline) and proton pump inhibitors, but increasing antibiotic resistance, especially to clarithromycin and metronidazole, poses a major challenge. Resistance mechanisms include mutations in drug targets, efflux pump overexpression, and enzymatic degradation of antibiotics. This has prompted exploration of alternative therapies targeting bacterial processes like urease activity, biofilm formation, and metabolic pathways (energy production, amino acid synthesis, iron acquisition). Natural compounds, such as chitosan and plant extracts, show promise in combating H. pylori growth and virulence. Vaccine development is also ongoing, with DNA vaccines showing potential for broad immune responses. However, no vaccine is yet close to widespread clinical use. Full article

Helicobacter pylori (H. pylori), a prevalent human pathogen affecting nearly half the global population, is a major contributor to chronic gastritis, peptic ulcer, and gastric cancer. H. pylori develops biofilms (BFs) allowing bacteria to evade the immune response. Differences in composition between planktonic and biofilm cells influence the host’s immune response, yet the specific biofilm components modulating this response remain uncharacterized. Considering the above, this study evaluated the effect of in vitro-generated H. pylori BF on the antibacterial activity of neutrophils. This work utilized sonication to obtain disaggregated H. pylori BF (d-BF-Hp) to challenge human neutrophils, assessing their bactericidal and phagocytic activity against Staphylococcus aureus. S. aureus survival in the presence of neutrophils was enhanced by 10 μg/mL of d-BF-Hp’s protein. Conversely, S. aureus survival was significantly lower at 30 µg/mL compared to 10 µg/mL d-BF-Hp. Furthermore, 10 and 30 µg/mL of d-BF-Hp significantly reduced the neutrophil phagocytosis rate. Our findings suggest that d-BF-Hp components diminish neutrophil bactericidal activity, although this effect was not observed at higher d-BF-Hp concentrations. Increased d-BF-Hp concentrations proportionally reduced neutrophil phagocytic capacity. Future work should explore the mechanisms underlying the alteration of neutrophil microbicidal properties. Full article

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the human stomach and is associated with several gastric diseases, including gastritis, peptic ulcer disease, and gastric cancer. The bacterium’s ability to thrive in the harsh gastric environment is due, to some extent, to its stress response mechanisms, with its heat shock proteins (HSPs) playing a putative, yet not fully understood, role in these adaptive processes. HSPs are a family of molecules, highly conserved throughout phylogenesis, that assist in protein folding, prevent aggregation, and ensure cellular homeostasis under stressful conditions. In H. pylori, HSPs contribute to survival in the stomach’s acidic environment and oxidative stress. Furthermore, they aid in the bacterium’s ability to adhere to gastric epithelial cells, modulate the host immune response, and form biofilms, all contributing to chronic infection and pathogenicity. The role of microbial HSPs in antibiotic resistance has also emerged as a critical area of research, as these proteins help stabilize efflux pumps, protect essential proteins targeted by antibiotics, and promote biofilm formation, thereby reducing the efficacy of antimicrobial treatments. Among bacterial HSPs, GroEL and DnaK are probably the major proteins that control most of the H. pylori’s functioning. Indeed, both proteins possess remarkable acid resistance, high substrate affinity, and dual roles in protein homeostasis and host interaction. These features make them critical for H. pylori’s adaptation, persistence, and pathogenicity in the gastric niche. In addition, recent findings have also highlighted the involvement of HSPs in the crosstalk between H. pylori and gastric epithelial cells mediated by the release of bacterial outer membrane vesicles and host-derived exosomes, both of these extracellular vesicles being part of the muco-microbiotic layer of the stomach and influencing cellular signalling and immune modulation. Considering their critical role in the survival and persistence of bacteria, microbial HSPs also represent potential therapeutic targets. Strategies aimed at inhibiting microbial HSP function, combined with conventional antibiotics or developing vaccines targeting microbial HSPs, could provide new avenues for the treatment of H. pylori infections and combat antibiotic resistance. This review explores the multifaceted roles of microbial HSPs in the pathogenesis of H. pylori, highlighting their contributions to bacterial adhesion, immune evasion, stress response, and antibiotic resistance. Full article

Helicobacter pylori (H. pylori) infection is a widespread gastric infectious disease, posing significant challenges due to the increasing prevalence of antibiotic resistance. This study aimed to evaluate the synergistic antibacterial activity of Takifugu obscurus skin peptides (TSPs) and the cell-free supernatant of Lactobacillus plantarum WUH3 (LCFS) in developing a potential green and efficient dietary supplement therapy. Using enzymatic hydrolysis and ultrafiltration techniques, the most bioactive peptide fraction, TSPb (1–3 kDa), was identified. The effects of TSPb and LCFS—both individually and in combination—on H. pylori biofilm function, membrane morphology, and internal structure were systematically analyzed using urease activity, N-phenyl naphthylamine (NPN) uptake, nucleic acid leakage, scanning electron microscopy (SEM), and infrared (IR) spectroscopy. The results showed that both LCFS and TSPb significantly inhibited H. pylori urease activity, with inhibition rates of 53.60% and 54.21% at 24 h, respectively, and the highest inhibition rate of 74.64% was observed with their combined treatment. SEM, NPN fluorescence, and nucleic acid leakage analyses revealed distinct mechanisms of action for each treatment. LCFS treatment caused membrane surface loosening and morphological deformation, while TSPb induced the formation of localized membrane pores. IR spectroscopy further confirmed that the combined treatment led to a more severe disruption of the lipid and protein structure within the bacterium. Overall, compared to individual treatments, the combination of TSPb and LCFS exhibited enhanced intracellular penetration and a more significant effect on bacterial viability. This study successfully identified TSPb as a highly bioactive peptide and elucidated its potential synergistic antibacterial mechanism with LCFS. These findings provide scientific evidence for the development of functional antimicrobial foods and gastric health dietary supplements, offering a promising strategy for the prevention and management of H. pylori infections. Full article

Helicobacter pylori (H. pylori) is a Gram-negative, spiral-shaped bacterium that colonizes the gastric epithelium and is associated with a range of gastrointestinal disorders, exhibiting a global prevalence of approximately 50%. Despite the availability of treatment options, H. pylori frequently reemerges and demonstrates increasing antibiotic resistance, which diminishes the efficacy of conventional therapies. Consequently, it is imperative to explore non-antibiotic treatment alternatives to mitigate the inappropriate use of antibiotics. This review examines H. pylori infection, encompassing transmission pathways, treatment modalities, antibiotic resistance, and eradication strategies. Additionally, it discusses alternative therapeutic approaches such as probiotics, anti-biofilm agents, phytotherapy, phototherapy, phage therapy, lactoferrin therapy, and vaccine development. These strategies aim to reduce antimicrobial resistance and enhance treatment outcomes for H. pylori infections. While alternative therapies can maintain low bacterial levels, they do not achieve complete eradication of H. pylori. These therapies are designed to bolster the immune response, minimize side effects, and provide gastroprotective benefits, rendering them suitable for adjunctive use alongside conventional treatments. Probiotics may serve as adjunctive therapy for H. pylori; however, their effectiveness as a monotherapy is limited. Photodynamic and phage therapies exhibit potential in targeting H. pylori infections, including those caused by drug-resistant strains, without the use of antibiotics. The development of a reliable vaccine is also critical for the eradication of H. pylori. This review identifies candidate antigens such as VacA, CagA, and HspA, along with various vaccine formulations, including vector-based and subunit vaccines. Some vaccines have demonstrated efficacy in clinical trials, while others have shown robust immune protection in preclinical studies. Nevertheless, each of the aforementioned alternative therapies requires thorough preclinical and clinical evaluation to ascertain their efficacy, side effects, cost-effectiveness, and patient compliance. Full article

Helicobacter pylori is a major pathogen associated with various gastric diseases. Despite decades of research, the treatment of H. pylori remains challenging. One of the primary mechanisms contributing to failures of therapies targeting this bacterium is genetic mutations in drug target sites, although the growing body of scientific data highlights that efflux pumps may also take part in this process. Efflux pumps are proteinaceous transporters actively expelling antimicrobial agents from the interior of the targeted cells and reducing the intracellular concentration of these compounds. Considering that efflux pumps contribute to both antimicrobial resistance and biofilm formation, an in-depth understanding of their properties may constitute a cornerstone in the development of novel therapeutics against H. pylori. In line with this, the aim of the current review is to describe the multitude of efflux pumps produced by H. pylori and present the data describing the involvement of these proteins in tolerance and/or resistance to various classes of antimicrobial substances. Full article

Background: Biofilm formation in Helicobacter pylori (H. pylori) helps bacteria survive antibiotic exposure and supports bacterial colonization and persistence in the stomach. Most of the published articles have focused on one aspect of the biofilm. Therefore, we conducted the current study to better understand the mechanism of biofilm formation, how the biofilm contributes to antibiotic resistance, and how the biofilm modifies the medication delivery mechanism. Methods: We conducted a literature review analysis of the published articles on the Helicobacter pylori biofilm between 1998 and 2024 from the PubMed database to retrieve eligible articles. After applying the inclusion and exclusion criteria, two hundred and seventy-three articles were eligible for our study. Results: The results showed that biofilm formation starts as adhesion and progresses through micro-colonies, maturation, and dispersion in a planktonic form. Moreover, specific genes modulate each phase of biofilm formation. Few studies have shown that mechanisms, such as quorum sensing and diffusible signal factors, enhance coordination among bacteria when switching from biofilm to planktonic states. Different protein expressions were also observed between planktonic and biofilm strains, and the biofilm architecture was supported by exopolysaccharides, extracellular DNA, and outer membrane vesicles. Conclusions: This infrastructure is responsible for the increased survival of bacteria, especially in harsh environments or in the presence of antibiotics. Therefore, understanding the biofilm formation for H. pylori is crucial. This study illustrates biofilm formation in H. pylori to help improve the treatment of H. pylori infection. Full article

Helicobacter pylori (H. pylori) is a bacterium known to be associated with a significant risk of gastric cancer in addition to chronic gastritis, peptic ulcer, and MALT lymphoma. Although only a small percentage of patients infected with H. pylori develop gastric cancer, Gastric cancer causes more than 750,000 deaths worldwide, with 90% of cases being caused by H. pylori. The eradication of this bacterium rests on multiple drug regimens as guided by various consensus. However, the efficacy of empirical therapy is decreasing due to antimicrobial resistance. In addition, biofilm formation complicates eradication. As the search for new antibiotics lags behind the bacterium’s ability to mutate, studies have been directed toward finding new anti-H. pylori agents while also optimizing current drug functions. Targeting biofilm, repurposing outer membrane vesicles that were initially a virulence factor of the bacteria, phage therapy, probiotics, and the construction of nanoparticles might be able to complement or even be alternatives for H. pylori treatment. This review aims to present reports on various compounds, either new or combined with current antibiotics, and their pathways to counteract H. pylori resistance. Full article

Helicobacter pylori is one of the most common bacterial pathogens worldwide and the main etiological agent of numerous gastric diseases. The frequency of multidrug resistance of H. pylori is growing and the leading factor related to this phenomenon is its ability to form biofilm. Therefore, the establishment of a proper model to study this structure is of critical need. In response to this, the aim of this original article is to validate conditions of the optimal biofilm development of H. pylori in monoculture and co-culture with a gastric cell line in media simulating human fluids. Using a set of culture-based and microscopic techniques, we proved that simulated transcellular fluid and simulated gastric fluid, when applied in appropriate concentrations, stimulate autoaggregation and biofilm formation of H. pylori. Additionally, using a co-culture system on semi-permeable membranes in media imitating the stomach environment, we were able to obtain a monolayer of a gastric cell line with H. pylori biofilm on its surface. We believe that the current model for H. pylori biofilm formation in monoculture and co-culture with gastric cells in media containing host-mimicking fluids will constitute a platform for the intensification of research on H. pylori biofilms in in vitro conditions that simulate the human body. Full article

The goal of this comprehensive review was to verify if the prevalence of Helicobacter pylori (Hp) bacteria in patients with dyspepsia is higher in the oral cavity of periodontal or non-periodontal patients. The bibliographic search was conducted on scientific studies published in PubMed, Cochrane Library, SciELO, and BVS. The focus question was: “In patients with dyspepsia and periodontitis, is the prevalence of Hp bacteria in the oral cavity higher than in patients with only dyspepsia or without any disease?” The inclusion criteria were human studies in English, Portuguese, or Spanish languages, published between 2000 and 2022, that included patients over the age of 18 and aimed to evaluate the presence of Hp bacteria in the oral cavity and in the protective mucosal layer of the gastric lining of patients with the diseases (periodontitis and dyspepsia) or without disease; clinical trials, randomized controlled clinical trials, comparative studies, case-control studies, cross-sectional studies, and cohort studies. The methodological quality evaluation of the included articles was performed using the Joanna Briggs Institute tools. The final scores could be of “Low” quality (at least two “no” [red] or ≥ five “unclear” found), “Moderate” quality (one “no” [red] was found or up to four “unclear” criteria were met), or “High” quality (all green [yes] or at maximum two “unclear”). Of 155 potentially eligible articles, 10 were included in this comprehensive review after the application of the eligibility criteria. The selected studies were scrutinized regarding the relationship between Hp colonization in the oral cavity and stomach, its impact on severity and complications of gastric infection, as well as the effect of the presence of oral and gastric Hp on dental and systemic parameters. Hp can colonize periodontal pockets regardless of its presence in the stomach. There was a higher prevalence of oral biofilm in dyspeptic patients with periodontal disease, and worse control of bleeding and low oral hygiene was observed in periodontal compared to non-periodontal patients. For que quality assessment, the scientific studies included presented low to moderate methodological quality. Conclusions: It is possible to conclude that Hp is a bacterium that can colonize dental plaque independently of the stomach and vice versa; however, when both diseases are found, its presence may be more significant. Supra and subgingival dental plaque may be a reservoir of Hp, suggesting that patients with gastric infections are more likely to have Hp in the oral cavity. The results must be carefully analyzed due to the limitations present in this review. Full article

Helicobacter pylori is associated with gastrointestinal diseases, and its treatment is challenging due to antibiotic-resistant strains, necessitating alternative therapies. Brazilian red propolis (BRP), known for its diverse bioactive compounds with pharmaceutical properties, was investigated for its anti-H. pylori activity, focusing on biofilm formation inhibition and eradication. BRP was tested against H. pylori (ATCC 43526) using several assays: time–kill, nucleotide leakage, biofilm formation inhibition (determining the minimum inhibitory concentration of biofilm of 50%—MICB₅₀, and cell viability), and biofilm eradication (determining the minimum eradication concentration of biofilm of 99.9%—MBEC). Standardization of H. pylori biofilm formation was also conducted. In the time–kill assay, BRP at 50 µg/mL eliminated all H. pylori cells after 24 h. The nucleotide leakage assay showed no significant differences between control groups and BRP-treated groups at 25 µg/mL and 50 µg/mL. H. pylori formed biofilms in vitro at 10⁹ CFU/mL after 72 h. The MICB₅₀ of BRP was 15.6 µg/mL, and at 500, 1000, and 2000 µg/mL, BRP eradicated all bacterial cells. The MBEC was 2000 µg/mL. These findings suggest that BRP has promising anti-H. pylori activity, effectively inhibiting and eradicating biofilms. Further studies are necessary to elucidate BRP’s mechanisms of action against H. pylori. Full article

Drug-resistant bacteria constitute a big barrier against current pharmacotherapy. Efforts are urgent to discover antibacterial drugs with novel chemical and biological features. Our work aimed at the synthesis, evaluation of antibacterial effects, and toxicity of licochalcone C (LCC), a naturally occurring chalcone. The synthetic route included six steps, affording a 10% overall yield. LCC showed effects against Gram-positive bacteria (MIC = 6.2–50.0 µg/mL), Mycobacterium species (MIC = 36.2–125 µg/mL), and Helicobacter pylori (MIC = 25 µg/mL). LCC inhibited the biofilm formation of MSSA and MRSA, demonstrating MBIC₅₀ values of 6.25 μg/mL for both strains. The investigations by fluorescence microscopy, using PI and SYTO9 as fluorophores, indicated that LCC was able to disrupt the S. aureus membrane, similarly to nisin. Systemic toxicity assays using Galleria mellonella larvae showed that LCC was not lethal at 100 µg/mL after 80 h treatment. These data suggest new uses for LCC as a compound with potential applications in antibacterial drug discovery and medical device coating. Full article

Bacterial surface display platforms have been developed for applications such as vaccine delivery and peptide library screening. The type V secretion system is an attractive anchoring motif for the surface expression of foreign proteins in gram-negative bacteria. SadA belongs to subtype C of the type V secretion system derived from Salmonella spp. and promotes biofilm formation and host cell adherence. The inner membrane lipoprotein SadB is important for SadA translocation. In this study, SadA was used as an anchoring motif to expose heterologous proteins in Salmonella typhimurium using SadB. The ability of SadA to display heterologous proteins on the S. typhimurium surface in the presence of SadB was approximately three-fold higher than that in its absence of SadB. Compared to full-length SadA, truncated SadAs (SadA⁸⁷⁷ and SadA²⁶⁹) showed similar display capacities when exposing the B-cell epitopes of urease B from Helicobacter pylori (UreB158–172aa and UreB349–363aa). We grafted different protein domains, including mScarlet (red fluorescent protein), the urease B fragment (UreBm) from H. pylori SS1, and/or protective antigen domain 4 from Bacillus anthracis A16R (PAD4), onto SadA⁸⁷⁷ or SadA¹²⁹². Whole-cell dot blotting, immunofluorescence, and flow cytometric analyses confirmed the localization of Flag×3-mScarlet (~30 kDa) and Flag×3-UreBm-mScarlet (~58 kDa) to the S. typhimurium surface using truncated SadA⁸⁷⁷ or SadA¹²⁹² as an anchoring motif. However, Flag×3-UreBm-PAD4-mScarlet (~75 kDa) was displayed on S. typhimurium using SadA¹²⁹². The oral administrated pSadBA¹²⁹²-FUM/StmΔygeAΔmurI and pSadBA⁸⁷⁷-FUM/StmΔygeAΔmurI could elicit a significant mucosal and humoral immunity response. SadA could thus be used as an anchoring motif for the surface expression of large heterologous proteins as a potential strategy for attenuated bacterial vaccine development. Full article

Helicobacter pylori infections are still an important health problem and are directly related to the development of gastric ulcer, gastric adenocarcinoma, mucosal lymphoid tissue lymphoma, and diabetes. At the same time, the number of substances/drugs effective against these bacteria is limited due to increasing resistance. Raw plant materials from various species of the Rubus genus—fruits and shoots—have shown antimicrobial activity in numerous studies against different bacteria, including H. pylori in a planktonic form. Research carried out on a model using fragments of intravenous infusions and triphenyl tetrazolium chloride (TTC) as a dye showed that the shoot extract of Rubus idaeus ‘Willamette’, the fruit extract of R. idaeus ‘Poranna Rosa’, R. idaeus and R. idaeus ‘Laszka’, and R. occidentalis Litacz’ prevent the formation of biofilm by H. pylori. Active concentrations inhibiting biofilm formation were 6.65 mg/mL for shoots and 16.65 mg/mL for fruits. However, in the resulting biofilm, the extract from the shoots of R. idaeus ‘Willamette’ and the fruit of R. idaeus ‘Poranna Rosa’ at a concentration of 16.65 mg/mL was active against living bacteria, and the remaining extracts showed such activity at a concentration of 33.3 mg/mL. In studies on the interaction of the extract with antibiotics on biofilm, the extract from the shoots of R. idaeus ‘Willamette’ showed synergy with doxycycline and levofloxacin, additivity with amoxicillin and clarithromycin, and neutrality with metronidazole. H. pylori biofilm research was carried out in a newly elaborated research model—culture on fragments of intravenous infusions with the addition of TTC as a marker of living bacterial cells. The research results may constitute the basis for the development of new combination therapies for the treatment of H. pylori infections, including its resistant strains. The proposed new biofilm research model, which is cheap and effective, may allow testing of new substances that are potentially more effective against H. pylori and other biofilm-forming bacterial strains. Full article