Bacterial immunobiology, host-pathogen modeling, and countermeasure development

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

Highly pathogenic bacteria such as Burkholderia pseudomallei and Coxiella burnetii are responsible for significant morbidity and mortality due to their associated human diseases, melioidosis and Q fever, respectively. These diseases can be acute or chronic and are associated with significant morbidity and mortality. The causative bacteria are profoundly infective and can survive in the environment robustly, highlighting their status as public health threats. There is a dearth of information regarding virulence determinants and host immune responses related to these pathogens. Thus, we have developed several models of bacterial-host interactions. We have utilized these models 1) to identify novel virulence determinants of C. burnetii, 2) better understand host immune responses, and 3) develop medical countermeasures for Q fever. Work with B. pesudomallei has recently begun and will be conducted using a similar experimental approach. Our experimental disease modeling systems combined with innovative methodologies (e.g., single cell sequencing, primary human cell models) have provided novel insight into the pathogenesis of and host response to C. burnetii. Our work on the C. burnetii virulence determinant, lipopolysaccharide, has allowed for safer research methodologies and more rigorous science. Our collaborative effort involving primary human alveolar macrophages has enhanced understanding of host responses to infection. Taken together, this work has led to a greater understanding of bacterial and host factors related to an important zoonotic pathogen, contributing to the development of medical countermeasures. The addition of B. pseudomallei will expand the impact of our program. Together, our work seeks to address health risks related to highly pathogenic bacteria and lead to disease prevention and treatment, bettering the health and quality of life of US citizens and beyond.