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Summary Antibiotic resistance in Helicobacter pylori has been growing worldwide with current treatment regimens. Development of new compounds for treatment of H. pylori infections is urgently required to achieve a successful eradication therapy in the future. Armeniaspirols, a novel class of natural products isolated from Streptomyces armeniacus, have been previously identified as antibacterial agents against Gram‐positive pathogens. In this study, we found that armeniaspirol A (ARM1) exhibited potent antibacterial activity against H. pylori, including multidrug‐resistant strains, with MIC range values of 4–16 μg ml‐1. The underlying mechanism of action of ARM1 against H. pylori involved the disruption of bacterial cell membranes. Also, ARM1 inhibited biofilm formation, eliminated preformed biofilms and killed biofilm‐encased H. pylori in a dose‐dependent manner. In a mouse model of multidrug‐resistant H. pylori infection, dual therapy with ARM1 and omeprazole showed efficient in vivo killing efficacy comparable to the standard triple therapy, and induced negligible toxicity against normal tissues. Moreover, at acidic pH 2.5, ARM1 exhibited a much more potent anti‐H. pylori activity than metronidazole. Thus, these findings demonstrated that ARM1 is a novel potent anti‐H. pylori agent, which can be developed as a promising drug lead for treatment of H. pylori infections.

Helicobacter pylori FabX, a dehydrogenase/isomerase flavoprotein, is required for unsaturated fatty acid synthesis. Here, the authors characterize FabX substrate recognition and catalytic mechanism, and reveal that it contains an atypical [4Fe-4S] cluster, which is essential and participates in the catalytic cycle.

The exchange coupling effect in nanocomposite samples with ferromagnetic (FM) body-centred tetragonal (bct) Fe nanoparticles (NPs) (~20 nm) embedded in an MnN antiferromagnetic (AFM) matrix is investigated. Both the bct Fe NPs control sample and the MnN (×nm)\bct Fe NPs\MnN (20–35 nm)\Ta (5 nm) nanocomposite samples are synthesized by a gas-phase condensation method. Both the coercivity and the remanence ratio of the nanocomposite samples are significantly enhanced compared with the bct Fe NPs sample. The coercivity and the remanence ratio increase with MnN thickness up to 30 nm and then decrease. Additionally, the exchange coupling strength between the bct Fe NPs and AFM MnN matrix is enhanced by magnetic field training. The magnetic field training leads to a higher coercivity and remanence ratio after one cycle of field-cooled hysteresis loop measurement. The coercivity of the composite sample increases by 80%, while the remanence ratio increases by around 30% compared with the bct Fe NPs sample. This work may provide an alternative approach to the design and manufacturing of FM-AFM exchange-coupled permanent magnets. [ABSTRACT FROM AUTHOR]

Cyclopropane fatty acids (CFAs) are synthetized by the addition of a methylene group from S-adenosyl-l-methionine across the carbon-carbon double bonds of unsaturated fatty acid chains of membrane phospholipids. This fatty acid cyclopropanation, catalyzed by the CFA synthase (CfaS) enzyme, occurs in many bacteria, including the human pathogen Helicobacter pylori. Although the cyclopropane modification was reported to play a key role in the adaptation in response to environmental stress, its role in H. pylori remains unknown. In this study, we showed that H. pylori HP0416 encodes a functional CfaS. The enzyme was demonstrated to be required for acid resistance, antibiotic resistance, intracellular survival and mouse gastric colonization, and cell membrane integrity. Moreover, the tool compound dioctylamine, which acts as a substrate mimic, directly inhibits the CfaS function of H. pylori, resulting into sensitivity to acid stress, increased antibiotic susceptibility, and attenuated abilities to avoid macrophage killing and to colonize mouse stomachs. These results validate CfaS as a promising antibiotic target and provide new potentials for this recognized target in future anti-H. pylori drug discovery efforts. [ABSTRACT FROM AUTHOR]