Interaction between Staphylococcus aureus and Pseudomonas aeruginosa in cystic fibrosis lungs


Fellow: Qing Tang, PhD

Mentor:  Joshua Woodward, PhD
Assistant Professor, Microbiology

Individuals with cystic fibrosis (CF) are highly susceptible to chronic polymicrobial lung infections, among which Staphylococcus aureus and Pseudomonas aeruginosa are most frequently isolated from the airways and mainly contribute to the morbidity and mortality of CF patients. Moreover, co-culture of these two pathogens are more virulent and exhibit higher antibiotic resistance, as well as can cause higher airway inflammation than monoculture infection with either species. P. aeruginosa and S. aureus are widely thought to have interspecies interaction with the mechanisms largely unknown. Producing cyclic di-adenosine monophosphate (cdA) is critical for the growth and immune capacity of S. aureus, whereas P. aeruginosa doesn’t produce this signaling molecule. In our preliminary data, cdA was observed to bind with P. aeruginosa cytoplasmic RNA-binding protein PA2582 with high specificity and affinity. PA2582 was observed to an intrinsic repressor for biofilm formation, and the repression activity was abrogated upon binding to cdA though unknown mechanisms. This study will characterize the regulatory mechanism of PA2583 in biofilm formation by identifying its sRNA targets and revealing the downstream signaling cascade induced by cdA. We will also illustrate the unknown mechanisms that affect how these two main pathogens of CF airways coexist and interact in planktonic and biofilm co-culture, as well as during coinfections using tissue culture and murine infection models. Thus, this study will reveal the mutually beneficial communication signaling pathways between P. aeruginosa and S. aureus in CF lungs, and provide new insights into elimination of polymicrobial infections.