Is Neisseria gonorrhoeae Initiating a Future Era of Untreatable Gonorrhea?: Detailed Characterization of the First Strain with High-Level Resistance to Ceftriaxone
Is Neisseria gonorrhoeae Initiating a Future Era of Untreatable Gonorrhea?: Detailed Characterization of the First Strain with High-Level Resistance to Ceftriaxone
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DOI：
10.1128/aac.00325-11
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发表时间：
2011-07-01
影响因子：
4.9
通讯作者：
Unemo, Magnus
中科院分区：
文献类型：
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作者：
Ohnishi, Makoto;Golparian, Daniel;Unemo, Magnus
最近，第一个淋病奈瑟菌菌株（H 041），是高度耐药的超广谱头孢菌素（ESC）头孢曲松，最后剩下的选择经验一线治疗，被分离。我们对H 041的表型和遗传进行了详细的表征，以证实这一发现，检查其抗菌素耐药性（AMR），并阐明耐药机制。H 041使用7种确认试验、细菌图谱（30种抗菌剂）、porB测序、N.淋病多抗原序列分型（NG-MAST）、多位点序列分型（MLST）和ESC抗性决定簇（佩纳、mtrR、penB、ponA和pilQ）的测序。使用合适的受体菌株进行转化以确认ESC抗性决定簇。H 041被指定为血清型Bpyust、MLST序列类型（ST）ST 7363和新NG-MAST ST ST 4220。H 041被证明对头孢曲松（2至4 μ g/ml，比任何先前描述的分离株高4至8倍）和所有其他头孢菌素以及大多数其他测试的抗菌剂具有高度耐药性。一个新的佩纳嵌合等位基因引起头孢曲松耐药。最后，N.淋病现在也显示出其产生头孢曲松耐药性的能力。虽然头孢曲松耐药的生物适应性在N。gonorrhoeae仍然未知，N.淋病可能很快成为真正的超级细菌，导致无法治愈的淋病。通过加强疾病控制活动减少全球淋病负担，结合更广泛的一般AMR控制战略，加强对AMR出现和传播机制的理解，这需要在全球范围内进行监测，以及全球（和国家）视角的公共卫生应对计划非常重要。最终，开发有效治疗淋病的新药是必要的。
Recently, the first Neisseria gonorrhoeae strain (H041) that is highly resistant to the extended-spectrum cephalosporin (ESC) ceftriaxone, the last remaining option for empirical first-line treatment, was isolated. We performed a detailed characterization of H041, phenotypically and genetically, to confirm the finding, examine its antimicrobial resistance (AMR), and elucidate the resistance mechanisms. H041 was examined using seven species-confirmatory tests, antibiograms (30 antimicrobials), porB sequencing, N. gonorrhoeae multiantigen sequence typing (NG-MAST), multilocus sequence typing (MLST), and sequencing of ESC resistance determinants (penA, mtrR, penB, ponA, and pilQ). Transformation, using appropriate recipient strains, was performed to confirm the ESC resistance determinants. H041 was assigned to serovar Bpyust, MLST sequence type (ST) ST7363, and the new NG-MAST ST4220. H041 proved highly resistant to ceftriaxone (2 to 4 mu g/ml, which is 4- to 8-fold higher than any previously described isolate) and all other cephalosporins, as well as most other antimicrobials tested. A new penA mosaic allele caused the ceftriaxone resistance. In conclusion, N. gonorrhoeae has now shown its ability to also develop ceftriaxone resistance. Although the biological fitness of ceftriaxone resistance in N. gonorrhoeae remains unknown, N. gonorrhoeae may soon become a true superbug, causing untreatable gonorrhea. A reduction in the global gonorrhea burden by enhanced disease control activities, combined with wider strategies for general AMR control and enhanced understanding of the mechanisms of emergence and spread of AMR, which need to be monitored globally, and public health response plans for global (and national) perspectives are important. Ultimately, the development of new drugs for efficacious gonorrhea treatment is necessary.