Virji M, Makepeace K, Peak I R, Ferguson D J, Jennings M P, Moxon E R
Department of Paediatrics, University of Oxford, John Radcliffe Hospital, UK.
Mol Microbiol. 1995 Nov;18(4):741-54. doi: 10.1111/j.1365-2958.1995.mmi_18040741.x.
The interplay between four surface-expressed virulence factors of Neisseria meningitidis (pili, Opc, capsule and lipopolysaccharide (LPS)) in host cell adhesion and invasion was examined using derivatives of a serogroup B strain, MC58, created by mutation (capsule, Opc) and selection of variants. To examine the role of Opc and of additional expression of pili, bacteria lacking the expression of Opa proteins were used. The effects of different LPS structures were examined in variants expressing either sialylated (L3 immunotype) or truncated non-sialylated (L8 immunotype) LPS. Studies showed that (i) pili were essential for meningococcal interactions with host cells in both capsulate and acapsulate bacteria with the sialylated L3 LPS immunotype, (ii) the Opc-mediated invasion of host cells by piliated and non-piliated bacteria was observed only in acapsulate organisms with L8 LPS immunotype, and (iii) expression of pili in Opc-expressing bacteria resulted in increased invasion. Investigations on the mechanisms of cellular invasion indicated that the Opc-mediated invasion was dependent on the presence of serum in the incubation medium and was mediated by serum proteins with arginine-glycine-aspartic acid (RGD) sequence. Cellular invasion in piliated Opc+ phenotype also required bridging molecules containing the RGD recognition sequence and appeared to involve the integrin alpha v beta 3 as a target receptor on endothelial cells. These studies extend the previous observations on variants of a serogroup A strain (C751) and show that Opc mediates cellular invasion in distinct meningococcal strains and provide confirmation of its mechanism of action. This is the first investigation that evaluates, using derivatives of a single strain, the interplay between four meningococcal surface virulence factors in host cell invasion.
利用B群菌株MC58的衍生物（通过突变（荚膜、Opc）和变体选择产生），研究了脑膜炎奈瑟菌的四种表面表达毒力因子（菌毛、Opc、荚膜和脂多糖（LPS））在宿主细胞黏附和侵袭中的相互作用。为了研究Opc的作用以及菌毛的额外表达，使用了缺乏Opa蛋白表达的细菌。在表达唾液酸化（L3免疫型）或截短的非唾液酸化（L8免疫型）LPS的变体中研究了不同LPS结构的影响。研究表明：（i）对于具有唾液酸化L3 LPS免疫型的有荚膜和无荚膜细菌，菌毛对于脑膜炎奈瑟菌与宿主细胞的相互作用至关重要；（ii）仅在具有L8 LPS免疫型的无荚膜生物体中观察到Opc介导的有菌毛和无菌毛细菌对宿主细胞的侵袭；（iii）在表达Opc的细菌中菌毛的表达导致侵袭增加。对细胞侵袭机制的研究表明，Opc介导的侵袭依赖于孵育培养基中血清的存在，并且由具有精氨酸 - 甘氨酸 - 天冬氨酸（RGD）序列的血清蛋白介导。有菌毛的Opc + 表型中的细胞侵袭也需要含有RGD识别序列的桥接分子，并且似乎涉及整合素αvβ3作为内皮细胞上的靶受体。这些研究扩展了先前对A群菌株（C751）变体的观察结果，表明Opc在不同的脑膜炎奈瑟菌菌株中介导细胞侵袭，并证实了其作用机制。这是首次使用单一菌株的衍生物评估四种脑膜炎奈瑟菌表面毒力因子在宿主细胞侵袭中的相互作用的研究。
