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Rational identification of Corynebacterium strains for use as probiotics

益生菌用棒状杆菌菌株的合理鉴定

基本信息

批准号：
10622610
负责人：
Matthew Scott Kelly
金额：
$ 19.43万
依托单位：
LURIE CHILDREN'S HOSPITAL OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-16 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10622610
关键词：
Accounting Adherence Bacteremia Bacteria Bacterial Pneumonia Biological Response Modifier Therapy Candidate Disease Gene Cells Cessation of life Child Child Mortality Childhood Comparative Genomic Analysis Competitive Binding Corynebacterium Data Defensins Development Disease Epithelial Attachment Epithelium Exclusion Exhibits Future Genes Genetic Genomics Genotype Goals Growth Human In Vitro Infection Infection prevention Intervention Invaded Knowledge Low Prevalence Lower respiratory tract structure Mediating Meningitis Modeling Nasopharynx Pathogenicity Peptides Phenotype Pneumococcal Infections Pneumonia Prevention Probiotics Proteomics Research Respiratory System Respiratory Tract Infections Risk Serotyping Skin Streptococcus pneumoniae Surface Testing Tissue Model Upper respiratory tract Vaccination Vaccines Work airway epithelium antimicrobial antimicrobial peptide bacterial resistance biobank colonization resistance comparative comparative genomics experimental study genome annotation genome sequencing infection risk insight microbiota mortality novel pan-genome pathogen pathogenic bacteria patient population prevent rational design repository respiratory respiratory colonization respiratory pathogen therapeutic candidate whole genome

项目摘要

Project Summary Pneumonia is the leading infectious killer of children. Bacterial pathogens, particularly Streptococcus pneumoniae, cause the most serious disease and mortality. Vaccination reduces invasive diseases such as bacteremia and meningitis caused by vaccine serotypes. However, vaccination does not equally lower the burden of pneumonia, and non-vaccine S. pneumoniae serotypes continue to emerge to cause respiratory and invasive infections. Thus, an opportunity exists for new ways to prevent these infections. Nasopharyngeal colonization precedes bacterial pneumonia and other respiratory infections, and the microbiota serves as a barrier to pathogen colonization and subsequent invasion of the lower respiratory tract. Our studies and others demonstrate that commensal, non-pathogenic Corynebacterium species are associated with a lower prevalence of colonization by bacterial respiratory pathogens, including S. pneumoniae. The data show an inverse correlation between the relative abundance of Corynebacterium in the nasopharyngeal microbiota and the risk of colonization by S. pneumoniae. These Corynebacterium species may be promising biotherapeutic candidates for development if they exert specific mechanistic control of bacterial respiratory pathogens. The overall objective herein is to identify the mechanisms by which Corynebacterium spp. colonize the human nasopharynx and exclude S. pneumoniae colonization. The rationale is that defining the mechanisms of these interspecies interactions will lead to identifying Corynebacterium spp. that exert multiple mechanisms of pathogen exclusion and are candidates for future biotherapeutics to prevent respiratory infections. The Specific Aims are: 1) Identify mechanisms by which Corynebacterium spp. adhere to the respiratory epithelium and inhibit Sp colonization through competitive adherence, and 2) Elucidate non-adherence mechanisms by which Corynebacterium spp. inhibit Sp colonization. This proposal will combine models of bacteria-host and bacteria-bacteria interactions to define mechanisms through which Corynebacterium inhibit S. pneumoniae colonization. We will leverage comparative genomics of a large Corynebacterium strain repository to identify accessory gene candidates that mediate respiratory epithelium attachment, competitive adherence with S. pneumoniae, and pneumococcal growth inhibition through secreted factors. The impact of this work is expected from the mechanistic insights and Corynebacterium strain identification that may lead to the first rationally-designed biotherapeutics to prevent pneumonia and other respiratory infections.

项目总结