ABSTRACT

Factors facilitating the chronicity of otitis media (OM) in children are, to date, not fully understood. An understanding of molecular factors aiding bacterial persistence within the middle ear during OM could reveal pathways required for disease. This study performed a detailed analysis of Streptococcus pneumoniae populations isolated from the nasopharynx and middle ear of one OM case. Isolates were assessed for growth in vitro and infection in a mouse intranasal challenge model. Whole genome sequencing was performed to compare the nasopharyngeal and middle ear isolates. The middle ear isolate displayed a reduced rate of growth and enhanced potential to transit to the middle ear in a murine model. The middle ear population possessed a single nucleotide polymorphism (SNP) in the IgA1 protease gene igA, predicted to render its product non-functional. Allelic exchange mutagenesis of the igA alleles from the genetic variant middle ear and nasopharyngeal isolates was able to reverse the niche-adaptation phenotype in the murine model. These results indicate the potential role of a SNP in the gene encoding the IgA1 protease, in determining S. pneumoniae adaptation to the middle ear during chronic OM. In contrast, a functional IgA1 protease was associated with increased colonisation of the nasopharynx.

中文翻译：

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IgA1 蛋白酶基因中的单核苷酸多态性决定肺炎链球菌在中耳炎期间对中耳的适应

摘要

迄今为止，尚未完全了解促进儿童中耳炎 (OM) 慢性化的因素。了解在 OM 期间有助于细菌在中耳内持续存在的分子因素可以揭示疾病所需的途径。本研究对从一例 OM 病例的鼻咽和中耳中分离的肺炎链球菌群进行了详细分析。对分离株进行体外生长评估和小鼠鼻内攻击模型中的感染。进行全基因组测序以比较鼻咽和中耳分离株。在小鼠模型中，中耳分离株显示出生长速度降低和转移到中耳的潜力增强。中耳种群在 IgA1 蛋白酶基因igA 中具有单核苷酸多态性 (SNP) ，预计会使其产品无功能。来自遗传变异中耳和鼻咽分离株的igA等位基因的等位基因交换诱变能够逆转小鼠模型中的生态位适应表型。这些结果表明编码 IgA1 蛋白酶的基因中的 S​​NP 在确定肺炎链球菌中的潜在作用适应慢性 OM 期间的中耳。相比之下，功能性 IgA1 蛋白酶与鼻咽部的定植增加有关。