新penA镶嵌等位基因致淋病奈瑟菌头孢菌素耐药的分子机制

The Molecular Mechanism of Neisseria Gonorrhoeae Resistance to Cephalosporin Which is Induced by the New penA Mosaic Allele

目的:追踪湖南首例头孢菌素耐药淋病奈瑟菌株wls18099分子流行病学信息,并探讨耐药机制。方法:采用NG-MAST对wls18099菌株分型。应用PCR扩增penA、mtrR、penB和ponA这4种与头孢菌素耐药密切相关的基因。将PCR产物测序得到的碱基数据与野生型菌株M32091比对,筛选出可疑耐药突变位点。用筛选的wls18099菌株耐药基因penA的PCR产物转化标准菌株WHO M、WHO L和临床分离的头孢菌素敏感菌株wls11020,验证其耐药性。结果:wls18099属于ST14155,其基因组含一种新的penAwlsⅩⅩⅩⅣ/K503P镶嵌等位基因。三种菌株转化该等位基因后均产生头孢曲松与头孢克肟耐药现象,MIC值上升4~62倍。结论:这种新的penA wlsⅩⅩⅩⅣ/K503P镶嵌等位基因可能导致wls18099菌株对头孢克肟和头孢曲松耐药。湖南及周边省份应加强对其监控,以防播散。

Objective:To trace the molecular epidemiological information of the first cephalosporin-resistant Neisseria gonorrhea strain wls18099 in Hu’nan,and to discuss the mechanism of drug resistance.Methods:The wls18099 strain was typed by NG-MAST.Four genes closely related to cephalosporin resistance, such as penA,mtrR,penB and ponA, were amplified by PCR.The base data which was obtained by sequencing the PCR product was aligned with the wild type strain M32091 to select a suspicious drug resistance mutation site.The PCR products of the wls18099 strain penA gene were used to transform the standard strains WHO M,WHO L and clinically isolated cephalosporin sensitive strain wls11020 to verify their drug resistance.Results:The wls18099 strain belongs to ST14155 and its genome contains a new penA wls ⅩⅩⅩⅣ/K503 P mosaic allele.The three strains have produced resistance to ceftriaxone and cefacoxime, and the MIC value increased by 4~62 times after transformation of penA allele.Conclusion:This new penA wls ⅩⅩⅩⅣ/K503 P mosaic allele may result in resistance of wls18099 strain to cefixime and ceftriaxone. It should strengthen monitoring to prevent wls18099 strain dissemination in Hu’nan and neighboring provinces.