Krasan G P, Cutter D, Block S L, St Geme J W
Edward Mallinckrodt Department of Pediatrics and Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.
Infect Immun. 1999 Jan;67(1):449-54. doi: 10.1128/IAI.67.1.449-454.1999.
The HMW1 and HMW2 proteins, Hia, and hemagglutinating pili are important adherence factors in nontypeable Haemophilus influenzae. To gain insight into the relative importance of these adhesins in nasopharyngeal colonization and localized respiratory tract disease, we assessed their expression in matched nasopharyngeal and middle ear isolates of nontypeable H. influenzae from 17 children with acute otitis media. In all patients, including 11 with bilateral disease, the matched isolates were isogenic based on total protein profiles and genomic fingerprints. Of the nasopharyngeal isolates, 14 expressed only HMW1/HMW2-like proteins, 1 expressed only Hia, 1 expressed only pili, and 1 expressed both Hia and pili. Further analysis revealed concordance between nasopharyngeal isolates and the matched middle ear isolates for expression of the HMW1/HMW2-like proteins and Hia. In contrast, in the two children whose nasopharynges were colonized by piliated organisms, the corresponding middle ear isolates were nonpiliated and could not be enriched for piliation. Nevertheless, Southern analysis revealed that these two middle ear isolates contained all five hif genes required for pilus biogenesis and had no evidence of major genetic rearrangement. In summary, the vast majority of isolates of nontypeable H. influenzae associated with acute otitis media express HMW1/HMW2-like proteins, with expression present in both the nasopharynx and the middle ear. A smaller fraction of nasopharyngeal isolates express pili, while isogenic strains recovered from the middle ear are often refractory to enrichment for piliation. We speculate that the HMW adhesins and Hia are important at multiple steps in the pathogenesis of otitis media while pili contribute to early colonization and then become dispensable.
高分子量蛋白1和高分子量蛋白2、Hia以及血凝菌毛是不可分型流感嗜血杆菌重要的黏附因子。为深入了解这些黏附素在鼻咽部定植和局部呼吸道疾病中的相对重要性，我们评估了它们在17例急性中耳炎患儿的配对鼻咽部和中耳不可分型流感嗜血杆菌分离株中的表达情况。在所有患者中，包括11例双侧患病患者，根据总蛋白谱和基因组指纹图谱，配对分离株是同基因的。在鼻咽部分离株中，14株仅表达高分子量蛋白1/高分子量蛋白2样蛋白，1株仅表达Hia，1株仅表达菌毛，1株同时表达Hia和菌毛。进一步分析显示，高分子量蛋白1/高分子量蛋白2样蛋白和Hia在鼻咽部分离株与配对中耳分离株中的表达具有一致性。相比之下，在两名鼻咽部被菌毛化生物体定植的儿童中，相应的中耳分离株无菌毛，且无法富集菌毛。然而，Southern分析显示，这两株中耳分离株含有菌毛生物合成所需的全部5个hif基因，且没有明显的主要基因重排证据。总之，与急性中耳炎相关的绝大多数不可分型流感嗜血杆菌分离株表达高分子量蛋白1/高分子量蛋白2样蛋白，在鼻咽部和中耳均有表达。一小部分鼻咽部分离株表达菌毛，而从中耳分离出的同基因菌株通常难以富集菌毛。我们推测，高分子量黏附素和Hia在中耳炎发病机制的多个步骤中起重要作用，而菌毛有助于早期定植，随后变得不再必要。
