Harrison Lee H, Jolley Keith A, Shutt Kathleen A, Marsh Jane W, O'Leary Mary, Sanza Laurie Thomson, Maiden Martin C J
Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
J Infect Dis. 2006 May 1;193(9):1266-74. doi: 10.1086/501371. Epub 2006 Mar 28.
The incidence of serogroup C and Y meningococcal disease increased in the United States during the 1990s. The cyclical nature of endemic meningococcal disease remains unexplained. The purpose of this study was to investigate the mechanisms associated with the increase in the incidence of meningococcal disease.
We characterized an increasing incidence of invasive serogroup C and Y meningococcal disease using population-based surveillance from 1992 through 2001. Isolates were characterized by multilocus sequence typing and antigen sequence typing of 3 outer membrane protein (OMP) genes: porA variable regions (VRs) 1 and 2, porB, and fetA VR.
For both serogroups, OMP antigenic shifts were associated with increased incidence of meningococcal disease. For serogroup Y, antigenic shift occurred through amino acid substitutions at all 3 OMPs--PorA VR 1 and 2, PorB, and FetA VR. For serogroup C, antigenic shift involved amino acid substitutions at FetA VR and, in some cases, deletion of the porA gene. On the basis of deduced amino acid sequences, the antigenic changes likely occurred by horizontal gene transfer.
Antigenic shifts were associated with increased incidence of serogroup C and serogroup Y meningococcal disease. For serogroup Y, the changes involved all OMP genes that were studied. Increases in the incidence of meningococcal disease may be caused, in part, by antigenic shift.
20世纪90年代,美国C群和Y群脑膜炎球菌病的发病率有所上升。地方性脑膜炎球菌病的周期性特征仍无法解释。本研究的目的是调查与脑膜炎球菌病发病率上升相关的机制。
我们利用1992年至2001年基于人群的监测,对侵袭性C群和Y群脑膜炎球菌病发病率的上升进行了特征分析。通过多位点序列分型和3个外膜蛋白(OMP)基因的抗原序列分型对分离株进行特征分析:PorA可变区(VRs)1和2、PorB和FetA VR。
对于这两个血清群,OMP抗原性转变均与脑膜炎球菌病发病率的上升相关。对于Y群,抗原性转变通过所有3个OMP(PorA VR 1和2、PorB和FetA VR)的氨基酸替换发生。对于C群,抗原性转变涉及FetA VR的氨基酸替换,在某些情况下还涉及porA基因的缺失。根据推导的氨基酸序列,抗原性变化可能是通过水平基因转移发生的。
抗原性转变与C群和Y群脑膜炎球菌病发病率的上升相关。对于Y群,这些变化涉及所有研究的OMP基因。脑膜炎球菌病发病率的上升可能部分是由抗原性转变引起的。