Cystic fibrosis (CF) is the most common lethal inherited disorder in Caucasians. It is caused by mutation of the CF transmembrane conductance regulator (CFTR) gene. A defect in the CFTR ion channel causes a dramatic change in the composition of the airway surface fluid, leading to a highly viscous mucus layer. In healthy individuals, the majority of bacteria trapped in the mucus layer are removed and destroyed by mucociliary clearance. However, in the lungs of patients with CF, the mucociliary clearance is impaired due to dehydration of the airway surface fluid. As a consequence, patients with CF are highly susceptible to chronic or intermittent pulmonary infections, often causing extensive lung inflammation and damage, accompanied by a decreased life expectancy. This mini review will focus on the different secretion mechanisms used by the major bacterial CF pathogens to release virulence factors, their role in resistance and discusses the potential for therapeutically targeting secretion systems.

Burkholderia cenocepacia is an opportunistic pathogen that is commonly isolated from patients with cystic fibrosis (CF). Several virulence factors have been identified, including extracellular enzymes that are secreted by type II and type VI secretion systems. The activity of these secretion systems is modulated by quorum sensing. Apart from the classical acylhomoserine lactone quorum sensing, B. cenocepacia also uses the diffusible signal factor system (DSF) i.e. 2-undecenoic acid derivatives that are recognized by specific receptors resulting in changes in biofilm formation, motility and virulence. However, quantitative information on alterations in the actual production and release of virulence factors upon exposure to DSF is lacking. We here describe an approach implementing microfluidics based chromatography combined with single reaction monitoring to quantify protein virulence factors in the secretome of B. cenocepacia.