Department of Molecular Biology, Division of Biotechnology, Finlay Institute, Ave 27, La Lisa, Havana 11600, Cuba.
Infect Genet Evol. 2010 May;10(4):546-54. doi: 10.1016/j.meegid.2010.02.002. Epub 2010 Feb 13.
We investigated the population genetics in collections of meningococci sampled in Cuba during the period 1983-2005, thereby covering a period before and after the introduction of an antimeningococcal B-C vaccine. A total of 163 case isolates and 210 isolates from healthy carriers were characterized by multilocus sequence typing (MLST) and sequence determination of porA, porB and fetA genes. A total of 56 sequence types (STs) including 28 new STs were identified among these isolates. The analysis of surface antigens revealed variants 3-1 and 3-8 to be prevalent for porB; variant F5-1 was the most common FetA epitope, and variants 19 and 15 corresponded to the prevalent variable regions 1 (VR1) and VR2 PorA epitopes, respectively. The strongest associations between specific surface protein variants and clonal complexes were detected in lineages ST-32 and ST-53. All ST-32 complex isolates possessed porB3 alleles, and the most frequent antigen combination among ST-32 complex isolates was P1.19,15;F5-1. Variants PorB3-64 at PorB and P1.30 at PorA VR2, in combination with the PorA VR1 variants P1.12-1, P1.7 and P1.7-2 as well as the FetA variants F1-2 and F1-7, dominated the ST-53 complex organisms. Furthermore, we observed a statistically significant association between the most frequent porA, porB and fetA alleles and strain invasiveness. Finally, this study showed that the application of VA-MENGOC-BC((R)), the Cuban antimeningococcal vaccine, reduced the number and frequency of the hypervirulent Clonal Complexes ST-32 and ST-41/44, and also impacted on other lineages. The vaccine also affected the genetic composition of the carrier-associated meningococcal isolates. The number of carrier isolates belonging to hypervirulent lineages decreased significantly after vaccination, and ST-53, a sequence type common in carriers, became the predominant ST.
我们调查了 1983 年至 2005 年期间在古巴采集的脑膜炎球菌分离株的群体遗传学,从而涵盖了引入抗脑膜炎球菌 B-C 疫苗前后的时期。总共对 163 例病例分离株和 210 例健康携带者分离株进行了多位点序列分型 (MLST) 和 porA、porB 和 fetA 基因序列测定。在这些分离株中鉴定出了 56 个序列型 (ST),包括 28 个新的 ST。表面抗原分析显示,porB 的变体 3-1 和 3-8 流行;变体 F5-1 是最常见的 FetA 表位,变体 19 和 15 分别对应于流行的可变区 1 (VR1) 和 VR2 PorA 表位。在 ST-32 和 ST-53 谱系中检测到特定表面蛋白变体与克隆复合体之间的最强关联。所有 ST-32 复合体分离株均携带 porB3 等位基因,ST-32 复合体分离株中最常见的抗原组合是 P1.19,15;F5-1。PorB 的变体 PorB3-64 和 PorA VR2 的 P1.30,与 PorA VR1 的变体 P1.12-1、P1.7 和 P1.7-2 以及 FetA 的变体 F1-2 和 F1-7 一起,主导了 ST-53 复合体生物体。此外,我们观察到最常见的 porA、porB 和 fetA 等位基因与菌株侵袭性之间存在统计学上显著的关联。最后,本研究表明,VA-MENGOC-BC((R))的应用,古巴的抗脑膜炎球菌疫苗,减少了数量和频率的 hypervirulent 克隆复合体 ST-32 和 ST-41/44,也影响了其他谱系。疫苗还影响了携带相关脑膜炎球菌分离株的遗传组成。疫苗接种后,属于 hypervirulent 谱系的携带分离株数量显著减少,而在携带者中常见的 ST-53 成为主要的 ST。