Nelson Aaron L, Roche Aoife M, Gould Jane M, Chim Kannie, Ratner Adam J, Weiser Jeffrey N
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6076, USA.
Infect Immun. 2007 Jan;75(1):83-90. doi: 10.1128/IAI.01475-06. Epub 2006 Nov 6.
Expression of a polysaccharide capsule is required for the full pathogenicity of many mucosal pathogens such as Streptococcus pneumoniae. Although capsule allows for evasion of opsonization and subsequent phagocytosis during invasive infection, its role during mucosal colonization, the organism's commensal state, remains unknown. Using a mouse model, we demonstrate that unencapsulated mutants remain capable of nasal colonization but at a reduced density and duration compared to those of their encapsulated parent strains. This deficit in colonization was not due to increased susceptibility to opsonophagocytic clearance involving complement, antibody, or the influx of Ly-6G-positive cells, including neutrophils seen during carriage. Rather, unencapsulated mutants remain agglutinated within lumenal mucus and, thus, are less likely to transit to the epithelial surface where stable colonization occurs. Studies of in vitro binding to immobilized human airway mucus confirmed the inhibitory effect of encapsulation. Likewise, pneumococcal variants expressing larger amounts of negatively charged capsule per cell were less likely to adhere to surfaces coated with human mucus and more likely to evade initial clearance in vivo. Removal of negatively charged sialic acid residues by pretreatment of mucus with neuraminidase diminished the antiadhesive effect of encapsulation. This suggests that the inhibitory effect of encapsulation on mucus binding may be mediated by electrostatic repulsion and offers an explanation for the predominance of anionic polysaccharides among the diverse array of unique capsule types. In conclusion, our findings demonstrate that capsule confers an advantage to mucosal pathogens distinct from its role in inhibition of opsonophagocytosis--escape from entrapment in lumenal mucus.
许多黏膜病原体（如肺炎链球菌）的完全致病性需要多糖荚膜的表达。虽然荚膜在侵袭性感染期间有助于逃避调理作用和随后的吞噬作用，但其在黏膜定植（即生物体的共生状态）过程中的作用仍不清楚。利用小鼠模型，我们证明无荚膜突变体仍能够在鼻腔定植，但与它们的有荚膜亲本菌株相比，其密度和持续时间有所降低。定植缺陷并非由于对涉及补体、抗体或Ly-6G阳性细胞（包括在携带过程中可见的中性粒细胞）流入的调理吞噬清除作用敏感性增加所致。相反，无荚膜突变体仍凝集在管腔内黏液中，因此不太可能转移到发生稳定定植的上皮表面。对固定化人呼吸道黏液的体外结合研究证实了荚膜的抑制作用。同样，每个细胞表达大量带负电荷荚膜的肺炎球菌变体不太可能黏附在涂有人黏液的表面，并且更有可能在体内逃避初始清除。用神经氨酸酶预处理黏液以去除带负电荷的唾液酸残基，可减弱荚膜的抗黏附作用。这表明荚膜对黏液结合的抑制作用可能是由静电排斥介导的，并为多种独特荚膜类型中阴离子多糖的优势提供了解释。总之，我们的研究结果表明，荚膜赋予黏膜病原体的优势与其在抑制调理吞噬作用中的作用不同——即从管腔内黏液的捕获中逃脱。
