The photograph shows a colony of Pseudomonas aeruginosa (confluent colony in the centre) secreting HQNO. This product protects Staphylococcus aureus (haze surrounding the P. aeruginosa colony) from the antibiotic (tobramycin) included in the medium. Image courtesy of Lucas Hoffman, University of Washington, Seattle, USA.

Pseudomonas aeruginosa and Staphylococcus aureus are two of the more important bacterial pathogens of humans, and both are frequently isolated from the lungs of cystic fibrosis (CF) patients. A recent report in Proceedings of the National Academy of Sciences USA now shows that P. aeruginosa simultaneously suppresses the growth, and enhances the aminoglycoside resistance of S. aureus through the action of its exoproduct, 4-hydroxy-2-heptylquinoline-N-oxide (HQNO). Indeed, prolonged exposure of S. aureus to HQNO selects for small-colony variants (SCVs) of the pathogen and stable antibiotic resistance.

Hospitalized patients, including those with CF, are frequently colonized with multiple pathogens, including S. aureus and P. aeruginosa. Interestingly, as CF patients acquire P. aeruginosa, S. aureus is cultured less frequently, although both pathogens are commonly found in respiratory cultures. Previous research showed that P. aeruginosa produces HQNO, an anti-staphylococcal molecule that suppresses the growth of many Gram-positive bacteria. Paradoxically, it was also shown that HQNO allowed some pathogens to grow in the presence of aminoglycoside antibiotics. As electron transport is required for aminoglycoside uptake, the authors reasoned that HQNO protects S. aureus from killing by inhibiting electron transport, and that the extent of S. aureus infection in the airways of CF patients represents a balance between the suppressive effects of HQNO produced by P. aeruginosa and the protection from antibiotics afforded by the exoproduct. To investigate these issues, the authors examined the effects of HQNO on the susceptibility of S. aureus to aminoglycoside under conditions that were clinically and physiologically relevant. They showed that the suppression of S. aureus growth by HQNO protected the pathogen from being killed by aminoglycoside antibiotics. Furthermore, the authors also demonstrated that prolonged growth of S. aureus with P. aeruginosa (or with physiological concentrations of HQNO) selected for S. aureus SCVs — SCVs of this pathogen can persist intracellularly and are notoriously difficult to detect, providing an explanation for the observation that S. aureus is cultured less frequently from CF patients following P. aeruginosa infection. Finally, the authors only detected HQNO in the sputum of CF patients that were infected with P. aeruginosa, providing evidence for the clinical relevance of HQNO production by P. aeruginosa and its subsequent effects on S. aureus within the environment of the CF lung.

As well as providing a fascinating example of pathogen interspecies interaction that impacts on virulence and the health of the host, the finding that P. aeruginosa selects for difficult-to-detect, antibiotic resistant S. aureus SCVs indicates that the role of this pathogen could be significantly underappreciated in all infections in which P. aeruginosa is present, a finding that also has practical implications for the treatment of CF patients.