Infections caused by multidrug-resistant bacteria with biofilm production ability are common and hardly treatable in Cystic Fibrosis (CF) patients, making research on new therapies a must. Bdellovibrio bacteriovorus is a Gram negative predator bacterium, able to destroy biofilms, that has already been proposed for treating bacterial infections. Preliminary our studies revealed the presence of B. bacteriovorus in healthy human intestinal mucosae, and showed B. bacteriovorus predatory activity versus Pseudomonas aeruginosa in sessile (biofilm) and planktonic forms, and Staphylococcus aureus biofilm. The aim of the present study is to evaluate B. bacteriovorus therapeutic potentiality in the treatment/prevention of pulmonary infections, induced by multidrug resistant bacterial strains isolated from respiratory samples of CF patients. The study will be carried out in experimental models representative of pulmonary infections in CF patients, such as pulmonary epithelial cell lines, CFT1 (derived from a CF patient and characterized by the F508 deletion) and HBE1 (the proficient counterpart of CFT1), and as a live model, the Galleria mellonella wax moth larvae.
Over the past decade CF lung infections by multidrug-resistant (MDR) bacteria are gradually increased, furthermore CF lung infections are almost always caused by biofilm-producing bacteria, which add a further obstacle to their removal (Bjarnsholt et al., 2009). Several studies, including ours, clearly indicate the predator bacteria B. bacteriovorus as a good candidate for the treatment of bacterial infections, as an alternative to antibiotics therapy. To corroborate/improve our previous observations we will perform predation assays on experimental model more relevant and evocative of the lung infections, in CF patients. Particularly we will employ human bronchial epithelial cell lines, proficient and deficient, for the cystic fibrosis transmembrane conductance regulator (CFTR) protein (HBE1 and CFT1, respectively); and we will perform predation assays in vivo, using Galleria mellonella model. As indicators for the evaluation of effective potentiality of B. bacteriovorus will be considered: i) a decrease in adhesion/invasion level of the selected MDR strains on pulmonary cells lines; ii) capacity to counteract infections in Galleria mellonella infected with the selected MDR strains.
Infections supported by multi-resistant bacteria, with biofilm production capacity, are common and difficult to treat in CF patients. The possibility to improve the management of lung infections by innovative strategies, bypassing the problem of antibiotic resistance, is certainly a point of great importance for ameliorate the quality of life of CF patients. The utilization of experimental models, more closely representing the lung infection in CF patients, will improve our knowledge on the use of B. bacteriovorus in a specific pathology, the CF. Our results will give us fundamental information to better understand the real potentiality of B. bacteriovorus as an alternative strategy to the conventional (and always more often ineffective) antibiotic therapy.