Hoffman Lab

Interspecies interactions, and the role of Staphylococcus aureus in CF lung disease

While most research and clinical effort in CF microbiology has focused on P. aeruginosa, the roles of the many other bacteria found in CF lungs are less well understood. Among those bacteria is S. aureus, which is more common among children with CF, often before P. aeruginosa is found. Many people with CF are infected with both species at the same time.

Colonies of the pathogen Staphylococcus aureus grow primarily as small-colony variants (SCVs) when grown in the presence of Pseudomonas aeruginosa, which often co-infects with S. aureus in many chronic infections. SCVs are resistant to many antibiotics and are often missed by clinical laboratories. From Hoffman et al., PNAS, 2006.

We found that P. aeruginosa produces a compound, HQNO, during infection of children with CF that alters the behavior of S. aureus. In response to HQNO, S. aureus grows very slowly, rendering it more difficult to detect, and also becomes highly resistant to tobramycin, and perhaps other antibiotics. This finding suggests at least two hypotheses of potential importance to CF and other chronic infections: First, S. aureus may be more common in CF patients than we detect. Second, and more generally, the interactions between the many species of microbes that infect CF patients may underlie clinical antibiotic failures. As we usually study one species of microbes at a time in the laboratory, such interspecies interactions may have eluded detection previously.

We are currently conducting a two-year pilot study to define the independent roles of S. aureus, P. aeruginosa, and their interspecies interactions in CF lung disease. From this study, we hope to answer the following questions:

  1. How common are S. aureus and P. aeruginosa, infecting both independently and together, among children with CF?
  2. What is the association of each species, and of coinfection, with clinical outcomes?
  3. What are the clinical consequences of the interspecies interactions between these two pathogens?

References:
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.

© 2014 Hoffman Laboratory, Division of Pulmonary and Sleep Medicine, Department of Pediatrics, University of Washington
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