Comanducci Maurizio, Bambini Stefania, Caugant Dominique A, Mora Marirosa, Brunelli Brunella, Capecchi Barbara, Ciucchi Laura, Rappuoli Rino, Pizza Mariagrazia
IRIS, Chiron Vaccines, via Fiorentina 1, 53100 Siena, Italy.
Infect Immun. 2004 Jul;72(7):4217-23. doi: 10.1128/IAI.72.7.4217-4223.2004.
NadA is a novel vaccine candidate recently identified in Neisseria meningitidis and involved in adhesion to host tissues. The nadA gene has been found in approximately 50% of the strains isolated from patients and in three of the four hypervirulent lineages of non-serogroup A strains. Here we investigated the presence of the nadA gene in 154 meningococcal strains isolated from healthy people (carrier strains). Only 25 (16.2%) of the 154 carrier isolates harbored the nadA gene. The commensal species Neisseria lactamica was also found not to have the nadA gene. Eighteen of the carrier strains belonged to the ET-5 and ET-37 hypervirulent clusters, indicating that only the 5.1% of the genuine carrier population actually harbored nadA (7 of 136 strains). Five of the seven strains harbored a novel allele of the nadA gene that was designated nadA4. The NadA4 protein was present on the bacterial surface as heat-stable high-molecular-weight oligomers. Antibodies against the recombinant NadA4 protein were bactericidal against homologous strains, whereas the activity against other NadA alleles was weak. In conclusion, the nadA gene segregates differently in the population of strains isolated from healthy individuals and in the population of strains isolated from patients. The presence of NadA can therefore be used as a tool to study the dynamics of meningococcal infections and understand why this bacterium, which is mostly a commensal, can become a severe pathogen.
NadA是最近在脑膜炎奈瑟菌中发现的一种新型疫苗候选物,参与对宿主组织的黏附。已在从患者分离出的约50%的菌株以及非A群菌株的四个高毒力谱系中的三个中发现了nadA基因。在此,我们调查了从健康人分离出的154株脑膜炎球菌菌株(携带菌株)中nadA基因的存在情况。154株携带菌株分离物中只有25株(16.2%)含有nadA基因。共生菌乳酸奈瑟菌也被发现没有nadA基因。18株携带菌株属于ET-5和ET-37高毒力簇,这表明只有5.1%的真正携带菌群体实际含有nadA(136株中的7株)。7株菌株中的5株含有nadA基因的一个新等位基因,被命名为nadA4。NadA4蛋白以热稳定的高分子量寡聚体形式存在于细菌表面。针对重组NadA4蛋白的抗体对同源菌株具有杀菌活性,而对其他NadA等位基因的活性较弱。总之,nadA基因在从健康个体分离出的菌株群体和从患者分离出的菌株群体中的分布不同。因此,NadA的存在可作为一种工具来研究脑膜炎球菌感染的动态,并理解为什么这种主要作为共生菌的细菌会成为一种严重病原体。