This study first reveals a positive correlation between the overexpression of the hefA efflux pump gene and clarithromycin resistance in clinical isolates of Helicobacter pylori. It also finds that 55% of resistant strains lack 23S rRNA mutations, suggesting that traditional genetic testing may underestimate the complexity of antibiotic resistance.
Literature Overview
This article, 'High Prevalence of hefA Efflux Pump Overexpression in Isolates of Helicobacter pylori Resistant to Clarithromycin,' published in the Antibiotics journal, reviews and summarizes the resistance mechanisms of Helicobacter pylori to clarithromycin, emphasizing that in addition to 23S rRNA mutations, overexpression of the hefA gene also plays an important role in resistance.
Background Knowledge
Helicobacter pylori is the main pathogen causing chronic gastritis, peptic ulcers, and gastric cancer, with a global infection rate as high as 90%. Clarithromycin is a first-line macrolide antibiotic for treating Helicobacter pylori infections, and its resistance has become a significant cause of treatment failure. Mutations at A2142G/A2143G in the 23S rRNA gene are the primary resistance mechanisms; however, this study found that nearly half of the resistant strains do not carry these mutations, suggesting other resistance mechanisms, such as efflux pump hyperactivation, may be involved. Clarithromycin resistance has led to reduced eradication rates, particularly in regions where resistance rates exceed 20%, significantly lowering the effectiveness of empirical treatments. Therefore, exploring resistance mechanisms beyond mutations, such as transcriptional regulation of the hefA gene, is crucial for optimizing clinical treatment and monitoring strategies.
Research Methods and Experiments
The research team used E-test methods to determine the minimum inhibitory concentration (MIC) of clarithromycin in 102 Helicobacter pylori gastric biopsy samples from southern Chile. 23S rRNA mutations were analyzed using PCR-RFLP combined with sequencing, while qPCR was employed to assess hefA gene expression levels. The study also conducted sociodemographic analyses to evaluate associations between resistant strains and variables such as residence and antibiotic use history.
Key Conclusions and Perspectives
Research Significance and Prospects
This study suggests that efflux pump expression analysis should be included in Helicobacter pylori resistance studies for a more comprehensive assessment of resistance mechanisms. Future phenotypic validation experiments (e.g., MIC determination with efflux pump inhibitors) are needed to confirm the functional role of hefA in resistance. Additionally, the epidemiological characteristics and fitness costs of resistant strains warrant systematic investigation to optimize regional treatment strategies.
Conclusion
This article reveals the diversity of clarithromycin resistance mechanisms in Helicobacter pylori and reports for the first time the high expression of the hefA efflux pump being associated with resistance. The study emphasizes that traditional genetic testing may overlook adaptive resistance mechanisms, leading to biases in clinical treatment strategies. In the future, resistance should be comprehensively assessed by integrating genetic mutations, efflux pump expression, and sociodemographic data to improve treatment success and reduce the spread of resistant strains.
