Community-level physiologic profiling of chronic infections
Most work and clinical attention in CF microbiology is focused on a small subset of bacteria and other microbes that are associated with clinical disease. However, recent studies have shed light on just how complex CF lung infections can be: The airways of most people with CF have many microbes, and at high densities. Exactly which of these microbes are “pathogens” is not well understood. Furthermore, our work studying only two of these many species, P. aeruginosa and S. aureus, suggests that complex communities of microbes may behave very differently than the single-species cultures we usually study in the laboratory. For example, P. aeruginosa and S. aureus interact in co-cultures, leading to changes in response to antibiotics by each species that wouldn’t be detected in single-species cultures.
Several studies have examined the species that are present in CF airways. However, very little attention has been focused on how the behavior of these multispecies communities differs from the behavior of single species. Using a combination of genetic, biochemical, physiologic, and microbiological methods, we hope to answer the following questions:
- Do the multispecies microbial communities in the airways of people with CF respond differently to antibiotics than do the component species?
- Are there treatments that would inhibit these communities better than our current antibiotic therapies, which usually target one species at a time?
- Does the presence of specific community compositions correlate better with clinical outcomes than does the presence or absence of one species (such as P. aeruginosa)?
Hoffman, LR; Déziel, E; D’Argenio, DA; Lépine, F; Emerson, J; McNamara, S; Gibson, RL; Ramsey, BW; Miller, SI. Selection for Staphylococcus aureus small-colony variants due to growth in the presence of Pseudomonas aeruginosa. Proc. Natl. Acad. Sci. USA, 2006. 103(52):19890-5.
Hoffman, LR; Richardson, AR; Houston, LS; Kulasekara, HD; Martens-Habbena, W; Klausen, M; Burns, JL; Stahl, DO; Hassett, D; Fang, F; and Miller, SI. Nutrient availability as a mechanism for selection of antibiotic tolerant Pseudomonas aeruginosa within the CF airway. PLoS Pathogens, 2010 Jan 8;6(1):e1000712.