Activity of antimicrobial peptides in the presence of polysaccharides produced by pulmonary pathogens

Abstract

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.

Molecular characterization of the PhoPQ-PmrD-PmrAB mediated pathway regulating polymyxin B resistance in Klebsiella pneumoniae CG43

“…In addition to the mucosa surfaces, antimicrobial peptides and proteins play important roles in the microbicidal activity of phagosome [41]. To investigate the effect of pmrF deletion in the bacterial survival within phagosome, phagocytosis assay was carried out.…”

Effects of Antimicrobial Peptides on Methanogenic Archaea

“…The effect obtained after treatment with Lpep 19-2.5 clearly demonstrates its severe interaction with capsular polysaccharides of M. stadtmanae, leading to a swelling of the surrounding layer, which is detached from the cell wall and almost twice as thick as the layer without treatment. The interaction of AMPs (␣-defensins, LL37, and hBD3) with bacterial exopolysaccharides of lung pathogens has already been described (13,34,52). Although this was found to reduce the activity of the AMPs on E. coli, an about 3-fold enlargement of the exopolysaccharide fibers has been observed using AFM (34).…”

Extreme Antimicrobial Peptide and Polymyxin B Resistance in the Genus Burkholderia

“…These resistance mechanisms include: changes to the cytoplasmic membrane in both Gram-negative and Gram-positive bacteria (Dorrer and Teuber, 1977; Peschel et al, 2001), alterations to teichoic acids in Gram-positive bacteria (Peschel et al, 1999) and LPS in Gram-negative bacteria (Vaara et al, 1981), efflux pumps (Shafer et al, 1998), proteases (Stumpe et al, 1998; Guina et al, 2000; Caldas et al, 2002; Belas et al, 2004), exopolysaccharides (Benincasa et al, 2009; Foschiatti et al, 2009), capsule polysaccharides (Campos et al, 2004; Spinosa et al, 2007; Llobet et al, 2008), modification of intracellular antimicrobial peptide targets (Vizán et al, 1991), and the coordination of resistance mechanisms through transcriptional regulation (Gunn and Miller, 1996; Guo et al, 1997; Humphreys et al, 1999; McPhee et al, 2003; Winfield et al, 2005; Kraus et al, 2008). …”