Studies on bacteriophages in respiratory diseases

PROJECT SUMMARY
Dr. Bollyky is a mid-career investigator who has developed a successful, translational research program
focused on bacteriophages – viruses that infect bacteria - and bacterial wound and airway infections. He is also
a highly productive research mentor, serving as a director of the physician-scientist training program for the
medical residency program as well as training numerous residents, fellows, and medical students in his own lab.
The goal of this K24 is to provide Dr. Bollyky with protected time to grow his patient-oriented research
program and mentor additional clinical fellows, junior faculty and other trainees in patient-oriented research. The
proposal also provides for dedicated time and resources to help Dr. Bollyky enhance his own mentoring skills,
obtain scientific and career guidance from an advisory committee, sharpen his skills in vaccinology and
microbiology, and expand his knowledge and technical skills in human clinical studies.
The scientific focus of this work is bacteriophages – viruses that infect bacteria – and their impact on bacterial
infections. Phages are abundant in the human body but their impact on human health is largely unknown.
The Bollyky lab has recently reported that phages produced by the major bacterial pathogen Pseudomonas
aeruginosa (Pa) promote chronic Pa infections. In particular, they have identified a novel mechanism by which
filamentous Pf phages produced by Pa contribute to antibiotic tolerance by functioning as structural elements in
Pa biofilms – slimy communities of bacteria and polymers that allow bacteria to colonize airways and other
surfaces. Pf phages organize host and microbial polymers in ways that produce a robust biofilm that resists
penetration by antibiotics, leading to antibiotic resistance. Their team recently published that Pf phages are
associated with heightened antibiotic resistance in patients with cystic fibrosis (CF), a genetic disease associated
with thick, tenacious sputum and chronic lung infections with Pa.
It may be possible to protect against Pa infection by targeting Pf phages. The Bollyky Lab recently developed
a vaccine that targets Pf phages to prevent Pa infections. However, it is unclear whether antibodies against Pf
phages naturally occur and whether these are protective against Pa infection.
Here, Dr. Bollyky will test the hypothesis that Pf phages contribute to antibiotic resistance and chronic
infections while Pf antibodies protect against this. In Aim 1 they will define how Pf phages contribute to antibiotic
tolerance in Pa biofilms. In Aim 2 they will define how Pf antibodies protect against Pa infections. Finally, in Aim
3 they will determine whether Pf and anti-Pf phage antibodies influence clinical outcomes in patients with CF.
Together, these studies will give rise to novel therapeutic targets and treatment strategies against Pa biofilm
infections and launch the careers of multiple young physician scientists. Protected time for career development
and mentoring will allow Dr. Bollyky to broaden the scope and influence of his and his trainees’ work and help to
sustain and grow the patient-oriented research enterprise of the NIAID and the NHLBI.

Grant Number: 5K24AI166718-04
NIH Institute/Center: NIH
Principal Investigator: Paul Bollyky