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Neutralizing the GBS hemolytic lipid toxin

中和 GBS 溶血脂质毒素

基本信息

批准号：
10647649
负责人：
Lakshmi Rajagopal
金额：
$ 82.33万
依托单位：
SEATTLE CHILDREN'S HOSPITAL
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：
2022-06-16 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10647649
关键词：
Adult Antibodies Antibody Formation Applications Grants Area Attenuated B-Lymphocytes Bacillus cereus Bacteria Bacterial Infections Bacteroides Biological Cell surface Cells Cerebral Palsy Clinical Cytotoxin Disease Elderly Erythrocytes Evaluation Genes Genus Mycobacterium Gram-Positive Bacteria Group Structure Hemolysin Hemolysis Human Immune Immune Sera Immunity Immunization Immunocompromised Host Infection Injury Integration Host Factors Intellectual functioning disability Lipids Macrophage Mediating Membrane Meningitis Microbe Modeling Morbidity - disease rate Mus Names Neonatal Neurologic Newborn Infant Ornithine Pathogenesis Pathology Perinatal Pigments Placenta Pneumonia Pregnancy Premature Birth Prevention Propionibacterium Proteins Pseudomonas Public Health Reporting Research Seizures Sepsis Streptococcal Infections Streptococcus Group B T-Lymphocyte Toxic effect Toxin Umbilical Cord Blood Vaccinated Vaccination Vaccines Vesicle Virulence Factors Woman Work adverse outcome analog aspirate chemical synthesis cytotoxic diabetic experimental study human morbidity human mortality immunogenicity improved in utero in vivo in vivo Model inhibiting antibody mast cell microbial mortality mouse model neonatal lung injury neutrophil pathogen pregnant prevent reproductive tract rhamnolipid screening stillbirth streptococcal group B hemolysin vaccine candidate vaccine response vaginal fluid

项目摘要

PROJECT SUMMARY Human morbidity and mortality due to bacterial infections continue to remain significant public health concern. Group B Streptococcus (GBS) or Streptococcus agalactiae cause invasive infections during pregnancy leading to preterm births, stillbirths or infections in newborns. Furthermore, GBS also cause infections in the normal, elderly, diabetic and immuno-compromised adults. Our work has shown that the hemolysin, which is a key virulence factor for GBS infections is a pigmented ornithine rhamnolipid also known as granadaene. This hemolytic lipid toxin is cytotoxic to a number of host cells leading to adverse outcomes to newborns and adult humans. The objectives of this proposal are to identify additional nontoxic analogs that can prevent toxin function during GBS infections using murine models of infection, to elucidate host immune mechanisms important for analog mediated immunity against this GBS toxin, to determine how membrane vesicles exacerbate GBS pathogenesis and if antibodies can attenuate their effects. Collectively, the results from these aims will be important and relevant for prevention of GBS infections in humans and will be relevant to other diseases caused by pathogens encoding toxic lipids.

项目总结