Streptococcus pneumoniae (pneumococcus) is a leading cause of severe infections among children and adults. Interactions between commensal microbes in the upper respiratory tract and S. pneumoniae are poorly described. In this study, we sought to identify interspecies interactions that modify the risk of S. pneumoniae colonization during infancy and to describe development of the upper respiratory microbiome during infancy in a sub-Saharan African setting. We collected nasopharyngeal swabs monthly (0–6 months of age) or bimonthly (6–12 months of age) from 179 mother–infant dyads in Botswana. We used 16S ribosomal RNA gene sequencing to characterize the nasopharyngeal microbiome and identified S. pneumoniae colonization using a species-specific PCR assay. We detect S. pneumoniae colonization in 144 (80%) infants at a median age of 71 days and identify a strong negative association between the relative abundance of the bacterial genera Corynebacterium within the infant nasopharyngeal microbiome and the risk of S. pneumoniae colonization. Using in vitro cultivation experiments, we demonstrate growth inhibition of S. pneumoniae by secreted factors from strains of several Corynebacterium species isolated from these infants. Finally, we demonstrate that antibiotic exposures and the winter season are associated with a decline in the relative abundance of Corynebacterium within the nasopharyngeal microbiome, while breastfeeding is associated with an increase in the Corynebacterium relative abundance. Our findings provide novel insights into the interspecies interactions that contribute to colonization resistance to S. pneumoniae and suggest that the nasopharyngeal microbiome may be a previously unrecognized mechanism by which environmental factors influence the risk of pneumococcal infections during childhood. Moreover, this work lays the foundation for future studies seeking to use targeted manipulation of the nasopharyngeal microbiome to prevent infections caused by S. pneumoniae.

肺炎链球菌（肺炎球菌）是儿童和成人严重感染的主要原因。上呼吸道共生微生物与肺炎链球菌之间的相互作用鲜有描述。在这项研究中，我们试图确定改变婴儿期肺炎链球菌定植风险的种间相互作用，并描述撒哈拉以南非洲地区婴儿期上呼吸道微生物组的发育。我们每月（0-6 个月大）或每两个月（6-12 个月大）从博茨瓦纳的 179 对母婴中收集鼻咽拭子。我们使用 16S 核糖体 RNA 基因测序来表征鼻咽微生物组并鉴定出肺炎链球菌使用物种特异性 PCR 测定进行定植。我们检测到 144 名 (80%) 婴儿的肺炎链球菌定植，中位年龄为 71 天，并发现婴儿鼻咽微生物组内棒状杆菌属的相对丰度与肺炎链球菌定植的风险之间存在强烈的负相关。通过体外培养实验，我们证明了从这些婴儿中分离出的几种棒状杆菌菌株的分泌因子对肺炎链球菌的生长抑制作用。最后，我们证明抗生素暴露和冬季与棒状杆菌相对丰度的下降有关在鼻咽微生物组中，母乳喂养与棒状杆菌相对丰度的增加有关。我们的研究结果为有助于对肺炎链球菌定植抵抗的种间相互作用提供了新的见解，并表明鼻咽微生物组可能是一种以前未被认识到的机制，环境因素通过该机制影响儿童时期肺炎球菌感染的风险。此外，这项工作为今后寻求使用鼻咽微生物组的靶向操作来预防肺炎链球菌引起的感染的研究奠定了基础。