Staphylococcus aureus sigma B-dependent emergence of small-colony variants and biofilm production following exposure toPseudomonas aeruginosa 4-hydroxy-2-heptylquinoline-N-oxide

Staphylococcus aureus and Pseudomonas aeruginosa are often found together in the airways of cystic fibrosis (CF) patients. It was previously shown that the P.

aeruginosa exoproduct 4-hydroxy-2-heptylquinoline-N-oxide (HQNO) suppresses the growth of S. aureus and provokes the emergence of small-colony variants (SCVs).

The presence of S. aureus SCVs as well as biofilms have both been associated with chronic infections in CF.

Results: We demonstrated that HQNO stimulates S.

aureus to form a biofilm in association with the formation of SCVs. The emergence of SCVs and biofilm production under HQNO exposure was shown to be dependent on the activity of the stress- and colonization-related alternative sigma factor B (SigB).

Analysis of gene expression revealed that exposure of a prototypical S. aureus strain to HQNO activates SigB, which was leading to an increase in the expression of the fibronectin-binding protein A and the biofilm-associated sarA genes.

Conversely, the quorum sensing accessory gene regulator (agr) system and the alpha-hemolysin gene were repressed by HQNO. Experiments using culture supernatants from P.

aeruginosa PAO1 and a double chamber co-culture model confirmed that P. aeruginosa stimulates biofilm formation and activates SigB in a S.

aureus strain isolated from a CF patient. Furthermore, the supernatant from P.

aeruginosa mutants unable to produce HQNO induced the production of biofilms by S. aureus to a lesser extent than the wild-type strain only in a S.

aureus SigB-functional background.

Conclusions: These results suggest that S. aureus responds to HQNO from P.

aeruginosa by forming SCVs and biofilms through SigB activation, a phenomenon that may contribute to the establishment of chronic infections in CF patients.

Author: Gabriel MitchellDavid SeguinAnn-Elise AsselinEric DezielAndre CantinEric FrostSophie MichaudFrancois Malouin
Credits/Source: BMC Microbiology 2010, 10:33

Published on: 2010-01-30

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