Project 2

Researchers: Nathan Fisher and Kendra Greenlee
Project Title: Innate Immune Evasion and Dysregulation by Stenotrophomonas maltophilia

Stenotrophomonas maltophilia is an emerging, multi-drug-resistant (MDR), opportunistic pathogen that frequently colonizes ventilator tubes and indwelling medical devices where it forms biofilms. Initial colonization can lead to severe, life-threatening infection. Approximately five percent of all cases of hospital-associated pneumonia in the United States are caused by this organism. Even more importantly, recent studies show that both incidence and prevalence are increasing, especially in immunocompromised, cystic fibrosis, chronic obstructive pulmonary disease (COPD), and cancer patients—demographic groups key to the research mission of the National Institutes of Health (NIH; Brook, 2012; Emerson et al., 2010; Metan et al., 2006). Clinical treatment is challenging because of S. maltophilia’s natural resistance to most classes of broad spectrum antibiotics. Moreover, resistance to antibiotics that first appear effective in vitro develops quickly in vivo due to upregulation of a plethora of efflux systems with broad specificity (Garrison, 1996). Based on successful approaches for other bacterial pathogens, our long-term goal is to develop treatment options that circumvent the S. malthophilia efflux systems by targeting secreted virulence factors or by pharmacologically bolstering the otherwise inadequate or inappropriate immune response. Currently, there is a critical knowledge gap with respect to how S. maltophilia avoids clearance by the immune system. Thus, our objective here is to identify the central components in both the bacterial virulence repertoire and the innate immune response to S. Maltophilia.