Grant: Project Grant

Respirologists and ICU physicians are faced with a frequent clinical problem when caring for patients with respiratory failure on ventilators in the intensive care unit (ICU) - lung secretions are sent to the lab for culture, and return positive for Candida, a genus of fungi not typically considered lung pathogens. However, it is well established that Candida in the respiratory tract is associated with increased risk of bacterial pneumonia. This seemingly paradoxical relationship between Candida fungi and deadly bacteria pneumonia leaves physicians with a conundrum - is Candida colonization of the lungs pathogenic or benign? Should this be treated, or not? A key reason why this remains a clinical problem in the ICU is that we lack a fundamental understanding how Candida "colonization" contributes to deadly bacterial infections in the lungs called ventilator-associated pneumonia (VAP). The objective of our research project is to address this key gap in knowledge by defining the impact of Candida in the lungs of ICU patients on bacterial pathogen growth and virulence, the lung microbiome, and its contributions to lung inflammation and damage. We will use cutting edge methodologies including advanced microbiome and immune analysis techniques to study samples collected from ICU patients on ventilators, together with a new lung-on-a-chip system that allows us to model the human lung in the lab and test new therapeutic approaches. Together, this research aims to revolutionize our understanding of this all-too- common clinical problem at the bedside, and enable mechanism-informed and personalized treatment approaches for vulnerable critically ill to improve VAP outcomes.