Characterization of viridans group streptococci from endophthalmitis

眼内炎草绿色链球菌的特征

• 批准号: 10245289
• 负责人: MARY E MARQUART
• 金额: $ 22.55万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10245289
• 关键词: Amino Acid Sequence; Antibiotics; Bacteria; Bacterial Proteins; Bacteriology; Bioinformatics; Case Study; Clinical; Collection; Deletion Mutagenesis; Development; Disease; Endophthalmitis; Enzymes; Erythrocytes; Etiology; Eye; Eye Infections; Future; Genbank; Gene Expression; Genes; Genetic; Genome; Genomics; Genus staphylococcus; Growth; Health; Heterogeneity; Horizontal Gene Transfer; Human; In Vitro; Infection; Injections; Investigation; Kinetics; Knowledge; Lead; Literature; Mining; Oligonucleotide Primers; Operative Surgical Procedures; Oral cavity; Organism; Oryctolagus cuniculus; Outcome; Pathogenesis; Patients; Peptide Hydrolases; Process; Prognosis; Proteins; Recombinant Proteins; Recombinants; Research; Resistance; Role; Sequence Analysis; Sheep; Streptococcus; Streptococcus Viridans Group; Streptococcus anginosus; Streptococcus gordonii; Streptococcus mitis; Streptococcus mutans; Streptococcus oralis; Streptococcus sanguis; Structure of retinal pigment epithelium; Substrate Specificity; Testing; Translating; Trauma; Variant; Virulence; Virulence Factors; Virulent; Visual; Vitreous humor; bacterial endophthalmitis; comparative; cytokine; epidemiology study; experimental study; extracellular; genome analysis; genome sequencing; in vivo; inhibitor/antagonist; normal microbiota; oral commensal; oral pathogen; pan-genome; protein degradation; protein purification; therapeutic development; therapy development; transcriptome; transcriptome sequencing; transcriptomics; whole genome

Project Summary/Abstract The viridans streptococci are classically considered oral commensals with cariogenic potential; however, these bacteria are also listed among the most common species that cause bacterial endophthalmitis. Exogenous bacterial endophthalmitis can occur following trauma, ocular surgery, or ocular injections. Antibiotics are used to treat this disease, however, antibiotics are only able to kill the bacteria and do not ameliorate the damage to the eye. Streptococcal species in particular are associated with very poor visual outcomes; despite treatment, evisceration or enucleation commonly occur. The immediate objective of this application is to characterize endophthalmitis strains of the viridans streptococci and identify their virulence factors. This objective is intended to initiate study into the broader, long-term objectives of determining the mechanisms of pathogenesis of this important group of species and identify potential targets for future therapies. Two major aims are proposed: 1) to investigate the role of bacterial protease HtrA in endophthalmitis and determine its vitreous and bacterial protein substrates, and 2) to analyze the pangenome and virulence transcriptome of endophthalmitis- causing strains. The first aim will be tested by function analysis of recombinant HtrA variants cloned from the viridans strains and by deletion mutagenesis of htrA from htrA-positive strains, as well as genetic addition of htrA to htrA-negative strains. The second aim will employ whole genome sequencing of 21 strains followed by bioinformatics pangenome analysis to identify conserved genes across the collection, and RNA-seq in vivo and in vitro to determine the virulence transcriptome of this group of species. Accomplishment of these aims will springboard the identification of key factors involved in ocular infection by these species. This research is expected to benefit patient ocular health in the long-term because the knowledge to be gained can aid future therapeutic development.

项目总结/文摘