Abstract
Cystic fibrosis (CF) patients are predisposed to chronic colonization of the major airways by Pseudomonas aeruginosa biofilms. Pulmonary infections, involving sessile bacteria, are the main cause of morbidity and mortality. As the eradication of antibiotic-resistant biofilms remains impossible, one key objective for the treatment of lung infections is to delay the switch of P. aeruginosa to a sessile phenotype. Few tools are currently available in hospital laboratories to evaluate the susceptibility of adherent microorganisms to antimicrobials. In this study, we used the Biofilm Ring Test®, for the achievement of Antibiofilmograms® on CF clinical isolates. In comparison to standard antibiograms, these procedures allow the investigation of antibiotic effects on the biofilm formation by bacteria. To confirm the inter-assay reproducibility, conventional Crystal Violet assays were performed. To mimic the pathologic reality of CF, we also used a model allowing the biofilm growth on CF-derived cells. Results obtained from these three different assays showed that amikacin and tobramycin, the two favored aminoglycosides in CF therapies, were able to prevent the early adhesion of P. aeruginosa isolates. This promising inhibitory effect of antimicrobials confirm that biofilm setting up is governed by adaptive responses and depends on environmental conditions, as opposite processes of biofilm induction by aminoglycosides were previously described in literature. Finally, Antibiofilmograms®, whose given results are in concordance with other in vitro antibiotic susceptibility testing, appear to be useful for the optimisation of CF therapies by the selection of antimicrobials able to delay chronic infection establishment.
Highlights
Cystic fibrosis (CF) is the most common inherited genetic disorder in Caucasian populations (Lyczak et al, 2002)
The realization of Antibiofilmograms R, through the Biofilm Ring Test R (BRT) device, allows the ability evaluation of antimicrobials to prevent the growth of bacteria in a sessile state, conducting to the formation of a biofilm
This biofilm formation leads to a chronic inflammation in the airways and owing to its antimicrobial resistance, makes eradication of the infection impossible (Moreau-Marquis et al, 2008b; Bhagirath et al, 2016)
Summary
Cystic fibrosis (CF) is the most common inherited genetic disorder in Caucasian populations (Lyczak et al, 2002). CFTR is involved in production of sweat, digestive fluids and mucus. In the CF lungs, the chloride transport defect, caused by non-functional proteins, results in altered airway physiology, impairment of mucociliary clearance and production. CF individuals are predisposed to chronic pulmonary microbial infections, which lead to respiratory failure, the primary cause of patient death (Davies et al, 2007; Farrell et al, 2017). Pseudomonas aeruginosa is the most frequent microorganism establishing chronic lung infections beyond infancy, in people with CF (Bhagirath et al, 2016). This opportunistic pathogen possesses features that contribute to its adaptation and persistence in the CF lungs, despite the availability of aggressive use of antibiotics (Høiby et al, 2001). One of the main reason explaining the resistance of P. aeruginosa in the lower tract of CF patients is its ability to grow as a biofilm (Moreau-Marquis et al, 2008b)
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