Ye Liping, Meng Fei, Mao Xinli, Zhang Yu, Wang Jun, Liu Yunhui, Zhu Wei, Gu Binbin, Huang Qin
Department of Gastroenterology, Taizhou Hospital of Zhejiang Province.
Department of Gastroenterology, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou.
Medicine (Baltimore). 2020 Aug 7;99(32):e20761. doi: 10.1097/MD.0000000000020761.
The regimens containing levofloxacin (LVX) have been recommended as an alternate to standard triple therapy to treat Helicobacter pylori infections and H pylori mixed infection always lead to H pylori chronic infection. Although the molecular mechanism of LVX resistance with gyrA gene mutation has been clearly understood in H pylori, other genes involved in antibiotic resistance remain unclear. Efflux pump plays an important role in clinically relevant multidrug resistance. Furthermore, the relationship between the strains with different LVX level-resistances from individuals is also unknown.Helicobacter pylori monoclonal strains were isolated from patients with eradication failure. E test was used to detect the minimal inhibitory concentration of LVX. One lower-level LVX-resistant clone and 2 higher-level LVX-resistant clones from the same patient were selected to sequence the complete genomes. Single-nucleotide variants (SNVs) and mutations were extracted and analyzed from gryA and resistance-nodulation-division family efflux genes.Two clones with higher-level resistance had the mutation pattern of Asn87Lys and one lower-level LVX-resistant clone had an Asp91Asn mutation. Compared to clones with higher-level resistance, the higher genetic variations were found in genes belonging to the resistance-nodulation-division family in H pylori strains with lower-level resistance to LVX. There were significantly more SNVs of Hp0970 (hefE) and Hp1329 (hefI) in the lower-level LVX-resistant clone than those in the higher-level LVX-resistant clones (P = .044).The mutation pattern of the Asn87Lys of the gyrA gene confers a higher resistance to LVX than that of the Asp91Asn in H pylori. Increase in the number of SNVs of the Hp0970 (hefE) and Hp1329 (hefI) genes change the resistance to LVX. Twelve mutations verified by Sanger sequencing in Hp0970 (hefE) and Hp1329 (hefI) may decrease resistant levels to LVX.
含左氧氟沙星（LVX）的治疗方案已被推荐作为治疗幽门螺杆菌感染的标准三联疗法的替代方案，而幽门螺杆菌混合感染总是导致幽门螺杆菌慢性感染。尽管幽门螺杆菌中左氧氟沙星耐药与gyrA基因突变的分子机制已被清楚了解，但其他与抗生素耐药相关的基因仍不清楚。外排泵在临床相关的多药耐药中起重要作用。此外，来自个体的不同左氧氟沙星水平耐药菌株之间的关系也不清楚。从根除失败的患者中分离出幽门螺杆菌单克隆菌株。采用E试验检测左氧氟沙星的最低抑菌浓度。从同一患者中选择1个低水平左氧氟沙星耐药克隆和2个高水平左氧氟沙星耐药克隆进行全基因组测序。从gyrA和耐药-固氮-分裂家族外排基因中提取并分析单核苷酸变异（SNV）和突变。两个高水平耐药克隆具有Asn87Lys突变模式，一个低水平左氧氟沙星耐药克隆具有Asp91Asn突变。与高水平耐药克隆相比，左氧氟沙星低水平耐药的幽门螺杆菌菌株中，属于耐药-固氮-分裂家族的基因存在更高的遗传变异。低水平左氧氟沙星耐药克隆中Hp0970（hefE）和Hp1329（hefI）的SNV明显多于高水平左氧氟沙星耐药克隆（P = 0.044）。在幽门螺杆菌中，gyrA基因的Asn87Lys突变模式比Asp91Asn赋予更高的左氧氟沙星耐药性。Hp0970（hefE）和Hp1329（hefI）基因SNV数量的增加改变了对左氧氟沙星的耐药性。通过桑格测序验证的Hp0970（hefE）和Hp1329（hefI）中的12个突变可能会降低对左氧氟沙星的耐药水平。
