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Abstract Introduction Helicobacter pylori exhibit considerable genetic diversity, especially in the cagA gene, which is prone to rearrangement, affecting gastric pathology. This study aims to identify changes in the cagA EPIYA motif patterns and gastric pathology during long-term colonization and to explore how factors such as smoking, alcohol consumption, gender, and age influence these changes. Methods Paired formalin-fixed paraffin-embedded (FFPE) gastric biopsies from 100 H. pylori-positive patients with digestive disorders obtained 10 years apart. After DNA extraction, the presence of H. pylori was detected by PCR amplification of the 16 S rRNA gene, and the cagA gene and its EPIYA motif patterns were identified by PCR using specific primers. Results Our results showed that 90% and 91% of primary and secondary samples were cagA positive respectively. The most frequent patterns were AB and ABC, and in 52% of patients, notable changes occurred in the motif pattern of cagA. The most frequent gastric pathology was chronic inflammation in both sets of samplings and in 45% of patients, changes in pathology outcomes were reported. A significant association was found between changes in pathology outcomes and gender (P = 0.01), with alterations observed in 24 male patients and 21 female patients, and between changes in pathology outcomes and smoking (P = 0.00). Among those with changes in pathology outcomes, only 18 patients had smoking habits, indicating a potential inverse correlation between smoking and the observed changes. A logistic regression analysis was performed to examine the association between smoking, gender, changes in cagA and alterations in gastric pathology. The finding revealed no significant relationship with smoking (P = 0.978 OR = 1.012) and gender (P = 0.901, OR = 0.950), but identified a significant association with changes in the cagA gene (p = 0.001, OR = 0.296), Conclusion he study highlights substantial heterogeneity in the cagA EPIYA motif patterns in long-term H. pylori colonization and notes an inverse relationship between pathology outcomes and smoking, warranting further investigation.

Abstract In this work, we have synthesized twenty five new 2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one derivatives bearing an aryl or heteroaryl methylene group on position 5 of thiazolidinone and evaluated their antimicrobial activity against Gram-positive and -negative bacteria as well as three metronidazole resistant Helicobacter pylori strains. Most of the compounds were very potent towards tested Gram-positive bacteria and showed an antibacterial efficacy substantially greater than ampicillin as the reference drug. However, no effectiveness was observed for the Gram-negative microorganisms. The compounds 9, 20 and 29 exhibited strong antimicrobial activity against Helicobacter pylori strains (inhibition zone > 30 mm) in 100 μg/disc and (inhibition zone > 20 mm) in 50 μg/disc. Taking these findings together, it seems that these potent antibacterial derivatives could be considered as promising agents for developing new anti-infectious drugs against microorganisms resistant to currently available antibiotics. Graphical Abstract

Our previous microscopic observations on the wet mount of cultured Candida yeast showed release of large extracellular vesicles (EVs) that contained intracellular bacteria (∼500–5000 nm). We used Candida tropicalis, to examine the internalization of nanoparticles (NPs) with different properties to find out whether the size and flexibility of both EVs and cell wall pores play role in transport of large particles across the cell wall.Candida tropicalis was cultured in N-acetylglucoseamine-yeast extract broth (NYB) and examined for release of EVs every 12 h by the light microscope. The yeast was also cultured in NYB supplemented with of 0.1%, 0.01% of Fluorescein isothiocyanate (FITC)-labelled NPs; gold (0.508 mM/L and 0.051 mM/L) (45, 70 and 100 nm), albumin (0.0015 mM/L and 0.015 mM/L) (100 nm) and Fluospheres (0.2 and 0.02%) (1000 and 2000 nm). Internalization of NPs was recorded with fluorescence microscope after 30 s to 120 min. Release of EVs mostly occurred at 36 h and concentration of 0.1% was the best for internalization of NPs that occurred at 30 s after treatment. Positively charged 45 nm NPs internalized into >90% of yeasts but 100 nm gold NPs destroyed them. However, 70 nm gold and 100 nm negatively-charged albumin were internalized into

After almost 40 years of the discovery and successful culture of the Helicobacter pylori, scientists are facing its resistance strategies that have challenged the world of biomedicine. Nanotechnology, on the other hand, has come to the aid of developing more efficient strategies against this bacterium in the arms race that we are involved in. Metallic nanoparticles with their fascinating properties, such as magnetism, ease of synthesis, biocompatibility, and wide range of sizes and shapes, have attracted lots of attention. The present review provides crucial information on these nanoparticles and the possible ways of their use for the eradication of H. pylori.

Background: Acinetobacter baumannii is an opportunistic pathogen associated with nosocomial infections. Extensive use of quinolones has resulted in an increase of resistance in this organism worldwide. Aim and Objectives: To study the association between PMQR genes, integron carriage as well as the possible role of AdeABC efflux pump in ciprofloxacin resistance as well as multidrug resistance in clinical isolates of A. baumannii. We studied the presence of Plasmid-Mediated-Quinolone Resistance (PMQR); AdeABC efflux pump genes and integron carriage in Intensive Care Unit (ICU) isolates of A. baumannii. Material and Methods: Fifty six non-duplicate clinical isolates of A. baumannii were obtained from two hospital ICUs in Tehran from March 5th 2014 to July 20th 2015. Susceptibility to 10 antibiotics was determined by disc diffusion. Presence of PMQR (aac(6')-Ib-cr, qnrA, qnrB, qnrC, qnrD and qnrS), adeABC efflux and class I and II integron genes were detected by Polymerase Chain Reaction (PCR). Results: All isolates were Multidrug-Resistant (MDR) among which, qnrB and aac(6')-Ib-cr were detected in 7.1% and 26.8% of the isolates, respectively. However, qnrA, qnrC, qnrD and qnrS were not observed. Presence of adeA and adeB was observed in 100% and adeC in 73.2% of the isolates. Overall, integron carriage was observed in (94.6%) of the isolates including qnrB positive and 73.3% of the aac(6')-Ib-cr carrying isolates. Conclusion: Our results show that quinolone resistance is not associated with PMQR genes. On the other hand, the AdeABC efflux pump is clearly responsible for MDR in our A. baumannii isolates including resistance to quinolones. No association was found between PMQR and integron carriage.

Nitro-containing heteroaromatic derivatives structurally related to nitroimidazole (Metronidazole) are being extensively evaluated against Helicobacter pylori isolates. On the other hand, 1,3,4-thiadiazole derivatives have also demonstrated promising antibacterial potential. In present study, we evaluated anti-H. pylori activity of novel hybrid molecules bearing nitroaryl and 1,3,4-thiadiazole moieties. Anti-H. pylori activity of novel 5-(5-nitroaryl)-1,3,4-thiadiazole derivatives bearing different bulky alkylthio side chains at C-2 position of thiadiazole ring, were assessed against three different metronidazole resistant H. pylori isolates by paper disk diffusion method. Most of the compounds demonstrated moderate to strong inhibitory response especially at 25 μg/disk. The structure-activity relationship study of the compounds demonstrated that introduction of different alkylthio moieties at C-2 position of thiadiazole ring alter the inhibitory activity which is mainly dependent on the type of C-5 attached nitrohetercyclic ring. The promising compound of this scaffold, bearing 1-methyl-5-nitroimidazole moiety at C-5 and α-methylbenzylthio side chain at C-2 position of thiadiazole ring, showed strong inhibitory response against metronidazole resistant H. pylori isolates at 12.5 μg/disk (the inhibition zone diameter at all evaluated concentrations (12.5- 100 μg/disk) is > 50 mm). Novel 5-(5-nitroaryl)-1,3,4-thiadiazole scaffold bearing different C-2 attached thiopendant moieties with promising anti-H. pylori potential were identified. Among different nitroheterocycles, 5-nitrofuran and 5-nitroimidazole moieties were preferable for the substitution at C-5 position of 1,3,4-thiadiazole ring. Introduction of different alkylthio side chains at C-2 position of central ring alter the inhibitory activity which is mainly dependent on the type of C-5 attached nitrohetercyclic ring. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) are resistant to hostile gastric environments and antibiotic therapy, reflecting the possibility that they are protected by an ecological niche, such as inside the vacuoles of human epithelial and immune cells. Candida yeast may also provide such an alternative niche, as fluorescently labeled H. pylori were observed as fast-moving and viable bacterium-like bodies inside the vacuoles of gastric, oral, vaginal and foodborne Candida yeasts. In addition, H. pylori-specific genes and proteins were detected in samples extracted from these yeasts. The H. pylori present within these yeasts produce peroxiredoxin and thiol peroxidase, providing the ability to detoxify oxygen metabolites formed in immune cells. Furthermore, these bacteria produce urease and VacA, two virulence determinants of H. pylori that influence phago-lysosome fusion and bacterial survival in macrophages. Microscopic observations of H. pylori cells in new generations of yeasts along with amplification of H. pylori-specific genes from consecutive generations indicate that new yeasts can inherit the intracellular H. pylori as part of their vacuolar content. Accordingly, it is proposed that yeast vacuoles serve as a sophisticated niche that protects H. pylori against the environmental stresses and provides essential nutrients, including ergosterol, for its growth and multiplication. This intracellular establishment inside the yeast vacuole likely occurred long ago, leading to the adaptation of H. pylori to persist in phagocytic cells. The presence of these bacteria within yeasts, including foodborne yeasts, along with the vertical transmission of yeasts from mother to neonate, provide explanations for the persistence and propagation of H. pylori in the human population. This Topic Highlight reviews and discusses recent evidence regarding the evolutionary adaptation of H. pylori to thrive in host cell vacuoles.