Abstract
The 2-alkyl-3-hydroxy-4(1H)-quinolone 2,4-dioxygenase HodC was previously described to cleave the Pseudomonas quinolone signal, PQS, which is exclusively used in the complex quorum sensing (QS) system of Pseudomonas aeruginosa, an opportunistic pathogen employing QS to regulate virulence and biofilm development. Degradation of PQS by exogenous addition of HodC to planktonic cells of P. aeruginosa attenuated production of virulence factors, and reduced virulence in planta. However, proteolytic cleavage reduced the efficacy of HodC. Here, we identified the secreted protease LasB of P. aeruginosa to be responsible for HodC degradation. In static biofilms of the P. aeruginosa PA14 lasB::Tn mutant, the catalytic activity of HodC led to an increase in viable biomass in newly formed but also in established biofilms, and reduced the expression of genes involved in iron metabolism and siderophore production, such as pvdS, pvdL, pvdA, and pvdQ. This is likely due to an increase in the levels of bioavailable iron by degradation of PQS, which is able to sequester iron from the surrounding environment. Thus, HodC, despite its ability to quench the production of virulence factors, is contraindicated for combating P. aeruginosa biofilms.
Highlights
Pseudomonas aeruginosa is one of the most important opportunistic human pathogens, causing a variety of life-threatening infections in immunocompromised patients (Gellatly and Hancock, 2013)
We investigated the effect of HodC on biofilms of P. aeruginosa PA14 strains deficient in the production of the protease LasB, which was found to be liable for proteolytic degradation of the enzyme
Since PQS is important for biofilm formation (Diggle et al, 2003), we analyzed the effect of HodC on P. aeruginosa biofilm development
Summary
Pseudomonas aeruginosa is one of the most important opportunistic human pathogens, causing a variety of life-threatening infections in immunocompromised patients (Gellatly and Hancock, 2013). P. aeruginosa is the dominant and most significant pathogen in patients suffering from cystic fibrosis, causing very difficult to treat pulmonary infections (Hutchison and Govan, 1999; Rajan and Saiman, 2002). It has a number of intrinsic resistance mechanisms including multidrug resistance efflux systems, low outer membrane permeability, and β-lactamases, produces a large arsenal of virulence factors, and forms robust biofilms (Gellatly and Hancock, 2013). PQS, besides its role as a QS signal molecule, modulates membrane properties (Mashburn and Whiteley, 2005), acts as ferric iron chelator (Bredenbruch et al, 2006; Diggle et al, 2007) and pro-oxidant (Häussler and Becker, 2008), and exerts pro-apoptotic and host immune modulatory activities (Hooi et al, 2004; Skindersoe et al, 2009; Hänsch et al, 2014)
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