Antimicrobial peptides (AMPs) are secreted in the airway and contribute to initial defence against inhaled pathogens. Infections
of the respiratory tract are a major cause of morbidity and mortality in preterm newborns and in patients with cystic fibrosis
(CF). In this latter group, the state of chronic lung infection is due to the ability of bacteria to grow as mucoid biofilm, a
condition characterised by overproduction and release of polysaccharides (PSs). In this study, we investigate the effect of PSs
produced by lung pathogens such as Pseudomonas aeruginosa, Klebsiella pneumoniae andmembers of the Burkholderia cepacia
complex on the antibacterial activity of structurally different peptides. The AMPs tested in this study include the cathelicidin
LL-37 and the β-defensin hBD-3 from humans, both released at the alveolar level, as well as peptides from other mammals, i.e.
SMAP-29, PG-1 and Bac7(1-35). Susceptibility assays, time killing and membrane permeabilization kinetics experiments were
carried out to establish whether PSs produced by lung pathogens may be involved in the poor defence reaction of infected
lungs and thus explain infection persistence. All the PSs investigated inhibited, albeit to a different extent, the antibacterial
activity of the peptides tested, suggesting that their presence in the lungs of patients with CF may contribute to the decreased
defence response of this district upon infection by PS-producing microorganisms. The results also show that inhibition of the
antibacterial activity is not simply due to ionic interaction between the negatively charged PSs and the cationic AMPs, but it
also involves other structural features of both interactors.
