Mora Marirosa, Bensi Giuliano, Capo Sabrina, Falugi Fabiana, Zingaretti Chiara, Manetti Andrea G O, Maggi Tiziana, Taddei Anna Rita, Grandi Guido, Telford John L
Chiron Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15641-6. doi: 10.1073/pnas.0507808102. Epub 2005 Oct 13.
Although pili have long been recognized in Gram-negative pathogens as important virulence factors involved in adhesion and invasion, very little is known about extended surface organelles in Gram-positive pathogens. Here we report that Group A Streptococcus (GAS), a Gram-positive human-specific pathogen that causes pharyngitis, impetigo, invasive disease, necrotizing fasciitis, and autoimmune sequelae has long, surface-exposed, pilus-like structures composed of members of a family of extracellular matrix-binding proteins. We describe four variant pili and show that each is recognized by a specific serum of the Lancefield T-typing system, which has been used for over five decades to characterize GAS isolates. Furthermore, we show that immunization of mice with a combination of recombinant pilus proteins confers protection against mucosal challenge with virulent GAS bacteria. The data indicate that induction of a protective immune response against these structures may be a useful strategy for development of a vaccine against disease caused by GAS infection.
虽然菌毛长期以来在革兰氏阴性病原体中被认为是参与黏附和侵袭的重要毒力因子,但对于革兰氏阳性病原体中的延伸表面细胞器却知之甚少。在此我们报告,A组链球菌(GAS)是一种革兰氏阳性的人类特异性病原体,可引起咽炎、脓疱病、侵袭性疾病、坏死性筋膜炎和自身免疫后遗症,它具有由细胞外基质结合蛋白家族成员组成的长的、表面暴露的、菌毛样结构。我们描述了四种变异菌毛,并表明每种菌毛都能被Lancefield T分型系统的特异性血清识别,该系统已被用于对GAS分离株进行特征鉴定超过五十年。此外,我们表明用重组菌毛蛋白组合免疫小鼠可使其免受有毒力的GAS细菌的黏膜攻击。数据表明,针对这些结构诱导保护性免疫反应可能是开发针对GAS感染所致疾病的疫苗的有用策略。