Ongoing Research | Overview
A major focus of Priebe Lab is on the mechanisms of protection of P. aeruginosa vaccines. Our team showed that Pseudomonas aroA deletion mutants, given intranasally, protect mice against acute Pseudomonas pneumonia and also against corneal infections. Antibodies alone can protect against corneal infections. However, for protection against pneumonia, both T cells and LPS-specific antibodies are needed. Rapid recruitment of neutrophils to the airways by the cytokine IL-17, which is secreted by helper CD4 T cells called Th17 cell, is critical for vaccine-induced protection in the non-neutropenic host, while CD4 T cells secreting GM-CSF are needed in the neutropenic host. Our lab also recently discovered Th17-stimulating Pseudomonas protein antigens that are effective intranasal vaccines in mice. Ongoing work is aimed at improving the potency and broadness of protection of these novel vaccines.
Another major effort of our lab centers on the investigation of bacterial and host factors important for P. aeruginosa infections. Our group uncovered the importance of the LPS O antigen for dissemination during pneumonia and the critical role of neutrophils and neutrophil elastase inhibitor in host defense in the respiratory tract and during gut-derived sepsis. We are also examining the roles of LPS and surface polysaccharides in the virulence of bacteria in the Burkholderia cepacia complex (BCC), including B. dolosa, which caused an outbreak in the early 2000s among cystic fibrosis patients at Boston Children's Hospital. We showed that a staphylococcal surface polysaccharide called poly N-acetyl-glucosamine is expressed by the BCC and is a target for antibody-mediated therapies, most notably for the nearly pan-resistant B. dolosa. In collaboration with the HMS Department of Systems Biology, our lab used whole-genome sequencing of B. dolosa isolates from the Boston Children's Hospital outbreak to identify bacterial genes under strong positive selection, suggesting potential new antibiotic targets, one of which is under active investigation. Ongoing work has extended these methods to single sputum samples and to other bacteria infecting the respiratory tract of critically ill children receiving mechanical ventilation.