Department of Biology, Santa Clara University, Santa Clara, California, USA.
Antimicrob Agents Chemother. 2012 Nov;56(11):5633-41. doi: 10.1128/AAC.00636-12. Epub 2012 Aug 20.
The recent emergence of Neisseria gonorrhoeae strains with decreased susceptibility to extended-spectrum cephalosporins is a major concern globally. We sequenced the genome of an N. gonorrhoeae multiantigen sequence typing (NG-MAST) ST1407 isolate (SM-3) with decreased susceptibility and resistance to oral extended-spectrum cephalosporins. The isolate was cultured in 2008 in San Francisco, CA, and possessed mosaic penA allele XXXIV, which is associated with an international clone that possesses decreased susceptibility as well as resistance to oral extended-spectrum cephalosporins globally. The genome sequence of strain NCCP11945 was used as a scaffold, and our assembly resulted in 91 contigs covering 2,029,064 bp (91%; >150× coverage) of the genome. Numerous instances of suspected horizontal genetic transfer events with other Neisseria species were identified, and two genes, opa and txf, acquired from nongonococcal Neisseria species, were identified. Strains possessing mosaic penA alleles (n = 108) and nonmosaic penA alleles (n = 169) from the United States and Europe (15 countries), cultured in 2002 to 2009, were screened for the presence of these genes. The opa gene was detected in most (82%) penA mosaic-containing isolates (mainly from 2007 to 2009) but not in any penA nonmosaic isolates. The txf gene was found in all strains containing opa but also in several (18%) penA nonmosaic strains. Using opa and txf as genetic markers, we identified a strain that possesses mosaic penA allele XXXIV, but the majority of its genome is not genetically related to strain SM-3. This implies that penA mosaic allele XXXIV was transferred horizontally. Such isolates also possessed decreased susceptibility and resistance to oral extended-spectrum cephalosporins. These findings support that genetic screening for particular penA mosaic alleles can be a valuable method for tracking strains with decreased susceptibility as well as resistance to oral extended-spectrum cephalosporins worldwide and that screening using only NG-MAST may not be sufficient.
淋球菌对扩展谱头孢菌素的敏感性降低的新菌株的出现是一个全球性的主要关注点。我们对来自加利福尼亚州旧金山的耐口服扩展谱头孢菌素的多抗原序列分型（NG-MAST）ST1407 分离株（SM-3）进行了基因组测序。该分离株于 2008 年培养，其 penA 等位基因 XXXIV 呈马赛克状，与一种国际克隆有关，该克隆在全球范围内对口服扩展谱头孢菌素具有较低的敏感性和耐药性。使用 NCCP11945 菌株的基因组序列作为支架，我们的组装得到了 91 个覆盖基因组的 2029064 bp（91%；>150×覆盖）的连续序列。鉴定出许多与其他奈瑟菌种发生疑似水平基因转移事件的实例，并鉴定出来自非淋球菌奈瑟菌种的两个基因 opa 和 txf。从美国和欧洲（15 个国家）培养的 2002 年至 2009 年的具有马赛克 penA 等位基因（n = 108）和非马赛克 penA 等位基因（n = 169）的菌株筛选了这些基因的存在。opa 基因在大多数（82%）携带 mosaic penA 等位基因的分离株（主要来自 2007 年至 2009 年）中被检测到，但在任何非 mosaic penA 分离株中均未检测到。txf 基因存在于所有携带 opa 的菌株中，但也存在于一些（18%）非 mosaic penA 菌株中。使用 opa 和 txf 作为遗传标记，我们鉴定出一个携带 mosaic penA 等位基因 XXXIV 的菌株，但该菌株的大部分基因组与其 SM-3 菌株没有遗传关系。这意味着 mosaic penA 等位基因 XXXIV 是水平转移的。这些分离株也对口服扩展谱头孢菌素的敏感性降低和耐药性。这些发现支持了针对特定 mosaic penA 等位基因的遗传筛选可以成为一种有价值的方法，用于追踪全球范围内对口服扩展谱头孢菌素的敏感性降低和耐药性的菌株，而仅使用 NG-MAST 进行筛选可能是不够的。
