Volatile hydrogen cyanide released by Pseudomonas aeruginosa provides a competitive advantage over Staphylococcus aureus in biofilm and in vivo lung environments

Diverse bacterial volatile compounds alter bacterial stress responses and physiology, but their contribution to population dynamics in polymicrobial communities is not well known. In this study, we showed that airborne volatile hydrogen cyanide (HCN) produced by a wide range of Pseudomonas aeruginosa clinical strains leads to at-a-distance inhibition of the growth of a wide array of Staphylococcus aureus strains. We determined that low oxygen level environments not only enhance P. aeruginosa HCN production but also increase S. aureus sensitivity to HCN, which impacts P. aeruginosa-S. aureus competition in microaerobic in vitro mixed biofilms as well as in an in vitro cystic fibrosis lung sputum medium. Consistently, we demonstrated that production of HCN provides a competitive advantage to P. aeruginosa in a mouse model of airways co-infected by P. aeruginosa and S. aureus . Our study therefore demonstrates that P. aeruginosa HCN contributes to local and distant airborne competition against S. aureus and potentially other HCN-sensitive bacteria in contexts relevant to cystic fibrosis and other polymicrobial infectious diseases. IMPORTANCE Airborne volatile compounds produced by bacteria are often only considered as attractive or repulsive scents, but they also directly contribute to bacterial physiology. Here we showed that volatile hydrogen cyanide (HCN) released by a wide range of Pseudomonas aeruginosa clinical strains inhibits Staphylococcus aureus growth in low oxygen in vitro biofilms or aggregates and in vivo lung environments. These results are of pathophysiological relevance, since lungs of cystic fibrosis patients are known to present microaerophilic areas and to be commonly associated with the presence of S. aureus and P. aeruginosa in polymicrobial communities. Our study therefore provides insights into how a bacterial volatile compound can contribute to the exclusion of S. aureus and other HCN-sensitive competitors from P. aeruginosa ecological niches. It opens new perspectives for the management or monitoring of P. aeruginosa infections in lower lung airway infections and other polymicrobial disease contexts. ### Competing Interest Statement The authors have declared no competing interest.