Swartley J S, Marfin A A, Edupuganti S, Liu L J, Cieslak P, Perkins B, Wenger J D, Stephens D S
Department of Medicine, Emory University School of Medicine, Atlanta, GA 30303, USA.
Proc Natl Acad Sci U S A. 1997 Jan 7;94(1):271-6. doi: 10.1073/pnas.94.1.271.
The different sialic acid (serogroups B, C, Y, and W-135) and nonsialic acid (serogroup A) capsular polysaccharides expressed by Neisseria meningitidis are major virulence factors and are used as epidemiologic markers and vaccine targets. However, the identification of meningococcal isolates with similar genetic markers but expressing different capsular polysaccharides suggests that meningococcal clones can switch the type of capsule they express. We identified, except for capsule, isogenic serogroups B [(alpha2-->8)-linked polysialic acid] and C [(alpha2-->9)-linked polysialic acid] meningococcal isolates from an outbreak of meningococcal disease in the U. S. Pacific Northwest. We used these isolates and prototype serogroup A, B, C, Y, and W-135 strains to define the capsular biosynthetic and transport operons of the major meningococcal serogroups and to show that switching from the B to C capsule in the outbreak strain was the result of allelic exchange of the polysialyltransferase. Capsule switching was probably the result of transformation and horizontal DNA exchange in vivo of a serogroup C capsule biosynthetic operon. These findings indicate that closely related virulent meningococcal clones may not be recognized by traditional serogroup-based surveillance and can escape vaccine-induced or natural protective immunity by capsule switching. Capsule switching may be an important virulence mechanism of meningococci and other encapsulated bacterial pathogens. As vaccine development progresses and broader immunization with capsular polysaccharide conjugate vaccines becomes a reality, the ability to switch capsular types may have important implications for the impact of these vaccines.
脑膜炎奈瑟菌表达的不同唾液酸（血清群B、C、Y和W - 135）和非唾液酸（血清群A）荚膜多糖是主要的毒力因子，用作流行病学标志物和疫苗靶点。然而，对具有相似遗传标志物但表达不同荚膜多糖的脑膜炎球菌分离株的鉴定表明，脑膜炎球菌克隆可改变其表达的荚膜类型。我们从美国太平洋西北部的一次脑膜炎球菌病暴发中鉴定出除荚膜外等基因的血清群B [（α2→8）连接的多聚唾液酸]和血清群C [（α2→9）连接的多聚唾液酸]脑膜炎球菌分离株。我们使用这些分离株以及血清群A、B、C、Y和W - 135原型菌株来确定主要脑膜炎球菌血清群的荚膜生物合成和转运操纵子，并表明暴发菌株中从B荚膜转换为C荚膜是多聚唾液酸转移酶等位基因交换的结果。荚膜转换可能是血清群C荚膜生物合成操纵子在体内转化和水平DNA交换的结果。这些发现表明，密切相关的毒力脑膜炎球菌克隆可能无法通过传统的基于血清群的监测被识别，并且可以通过荚膜转换逃避疫苗诱导的或天然的保护性免疫。荚膜转换可能是脑膜炎球菌和其他有荚膜细菌病原体的一种重要毒力机制。随着疫苗研发的进展以及更广泛地使用荚膜多糖结合疫苗进行免疫接种成为现实，转换荚膜类型的能力可能对这些疫苗的影响具有重要意义。
