Center for Research on the Respiratory Microbiota of African Children (ReMAC)

非洲儿童呼吸道微生物群研究中心（ReMAC）：摘要 上呼吸道的微生物群（微生物群落）在呼吸道疾病的发展中起着关键作用。 儿童下呼吸道感染（LRTI）。大多数重要的细菌性LRTI病原体也在 鼻咽（NP），通常作为儿童LRTI的感染源以及储存器 传染给其他孩子我们召集了一个跨学科的研究人员合作， 在南非、冈比亚和马拉维的三个领先的非洲研究机构， 中心在美国，以解决关键问题的决定因素，组成和生物意义的， 非洲儿童上呼吸道的微生物群。我们将利用现有的几个大型队列和样本 知识库进行三个互补但不相互依赖的研究项目，每个项目在多个 非洲网站第一个项目将侧重于NP微生物群（细菌、真菌）的全面描述 和病毒成分）在健康的非洲儿童在生命的第一年，使用纵向，经常 抽样队列。我们还将研究NP微生物群在抗定植中的作用， 呼吸道病原体，肺炎链球菌，包括调节疫苗诱导的保护。的 第二个项目将调查NP微生物群的作用，包括考虑抗菌素耐药性， 非洲儿童LRTI的发病率、严重程度和复发率。第三个项目将审查 季节性、吸入环境暴露（或污染物）、家庭灰尘 微生物群，以及来自南非和冈比亚的儿童的NP和口咽部的微生物群。我们 将使用扩增子测序来确定微生物群的细菌和真菌成分，靶向核酸 对病毒成分进行酸扩增测试，并进行鸟枪宏基因组测序以补充， 验证并扩展我们的发现。我们将应用统计建模工具，包括那些来自生态学， 了解微生物群的进化、内部相互作用和决定因素。 我们将建立一个非洲儿童呼吸道微生物群研究中心， 通过建立一个可持续的合作网络，建设非洲呼吸道微生物群研究的能力 非洲和美国的调查人员，重点是专门培训，研究生学习，技术转让和 职业发展。若能顺利完成建议的工作， 鼻咽生态学和LRTI的发病机制，促进诊断或 LRTI儿童的预后工具，提供了对微生物群的治疗操作是否 可能是可取的，并确定可改变的风险因素， 微生物群 1

Center for Research on the Respiratory Microbiota of African Children (ReMAC): Abstract The microbiota (community of microorganisms) of the upper airways plays a key role in the development of lower respiratory tract infection (LRTI) in children. Most of the important bacterial LRTI pathogens also colonize the nasopharynx (NP), which often serves as the source of infection for LRTI in a child as well as the reservoir for transmission to other children. We have assembled an interdisciplinary collaboration between investigators at three leading African research institutions, in South Africa, The Gambia and Malawi, and a leading genomic center in the USA to address key questions on the determinants, composition and biological significance of the microbiota of the upper airways in African children. We will leverage several large existing cohorts and sample repositories to conduct three complementary but not co-dependent research projects, each done at multiple African sites. The first project will focus on comprehensive description of the NP microbiota (bacterial, fungal and viral components) in healthy African children over the first year of life, using longitudinal, frequently sampled cohorts. We will also study the role of the NP microbiota in resistance to colonization with the respiratory pathogen, Streptococcus pneumoniae, including modulation of vaccine-induced protection. The second project will investigate the role of the NP microbiota, including consideration of antimicrobial resistance, in the incidence, severity, and recurrence of LRTI in African children. The third project will examine the association between seasonality, inhaled environmental exposures (or pollutants), the household dust microbiota, and the microbiota of the NP and oropharynx in children from South Africa and The Gambia. We will use amplicon sequencing to define the bacterial and fungal components of the microbiota, targeted nucleic acid amplification testing for the viral component, and shotgun metagenomic sequencing to complement, validate and extend our findings. We will apply statistical modeling tools, including those derived from ecology, to understand the evolution of, interactions within, and determinants of, the microbiota. We will develop a Center for Research into the Respiratory Microbiota of African Children (ReMAC) which will build capacity for respiratory microbiota research in Africa, by establishing a sustainable, collaborative network of African and US investigators, with focus on specialized training, postgraduate study, technology transfer and career development. Successful completion of the proposed work will enhance our understanding of the ecology of the nasopharynx and of the pathogenesis of LRTI, promote the development of diagnostic or prognostic tools for children with LRTI, provide insight into whether therapeutic manipulation of the microbiota may be desirable and identify modifiable risk factors which negatively influence the composition of the microbiota.   1