Research Centre for Infectious Diseases, Australian Centre for Antimicrobial Resistance Ecology, and Department of Molecular and Biomedical Science, The University of Adelaide, 5005, Adelaide, Australia.
South Australian Genomics Centre, South Australian Health & Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia.
Pathog Dis. 2021 Jan 9;79(1). doi: 10.1093/femspd/ftaa077.
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.
迄今为止，导致儿童中耳炎（OM）慢性化的因素尚未完全明了。了解有助于细菌在 OM 期间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 OM 患者的鼻咽部和中耳分离出的肺炎链球菌（Streptococcus pneumoniae）种群进行了详细分析。评估了分离株在体外的生长情况，并在小鼠鼻腔挑战模型中进行了感染实验。对全基因组进行测序，比较鼻咽部和中耳分离株。结果发现，与鼻咽部分离株相比，中耳分离株的生长速度较慢，在小鼠模型中更容易转移到中耳。该中耳分离株的 IgA1 蛋白酶基因（igA）中存在单核苷酸多态性（SNP），预计会使其产物失去功能。从中耳和鼻咽部遗传变异分离株的 IgA 等位基因进行等位基因交换突变，可在小鼠模型中逆转定殖表型。这些结果表明，编码 IgA1 蛋白酶的基因中的 SNP 可能在确定肺炎链球菌在慢性 OM 期间适应中耳方面发挥作用。相比之下，功能性 IgA1 蛋白酶与鼻咽部定植增加有关。
