Activity of antimicrobial peptides in the presence of polysaccharides produced by pulmonary pathogens.
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 and members 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 beta-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.
Benincasa
M
M
Department of Life Sciences, University of Trieste, I-34127 Trieste, Italy.
Mattiuzzo
M
M
Herasimenka
Y
Y
Cescutti
P
P
Rizzo
R
R
Gennaro
R
R
D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000382:microbiology; D042726:Burkholderia mallei / Q000187:drug effects / Q000378:metabolism; D054804:Cathelicidins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D003550:Cystic Fibrosis / Q000382:microbiology; D004347:Drug Interactions; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000378:metabolism; D008171:Lung Diseases / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D011135:Polysaccharides, Bacterial / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D011135:Polysaccharides, Bacterial