Different Dose-Dependent Modes of Action of C-Type Natriuretic Peptide on Pseudomonas aeruginosa Biofilm Formation

Abstract

We have previously shown that the C-type Natriuretic Peptide (CNP), a peptide produced by lungs, is able to impact Pseudomonas aeruginosa physiology. In the present work, the effect of CNP at different concentrations on P. aeruginosa biofilm formation was studied and the mechanisms of action of this human hormone on P. aeruginosa were deciphered. CNP was shown to inhibit dynamic biofilm formation in a dose-dependent manner without affecting the bacterial growth at any tested concentrations. The most effective concentrations were 1 and 0.1 µM. At 0.1 µM, the biofilm formation inhibition was fully dependent on the CNP sensor protein AmiC, whereas it was only partially AmiC-dependent at 1 µM, revealing the existence of a second AmiC-independent mode of action of CNP on P. aeruginosa. At 1 µM, CNP reduced both P. aeruginosa adhesion on glass and di-rhamnolipid production and also increased the bacterial membrane fluidity. The various effects of CNP at 1 µM and 0.1 µM on P. aeruginosa shown here should have major consequences to design drugs for biofilm treatment or prevention.

Bacterial association and comparison between lung and intestine in rats

“…The pulmonary bacteria in the context of human pulmonary health is mainly associated with respiratory diseases [20][21][22]. For example, Pseudomonas aeruginosa can cause chronic respiratory infections in the lungs [23][24][25]. Therefore, human body need to maintain an optimum level of bacteria.…”

Host Peptidic Hormones Affecting Bacterial Biofilm Formation and Virulence

“…It was observed that, whereas hBNP and hCNP have no impact at 1 and 0.1 µM on P. aeruginosa growth [37, 68], bacterial exposure to these peptides at 1 µM stimulates the virulence of P. aeruginosa and P. fluorescens [37, 38]. In addition, both hBNP and hCNP at 0.1 µM strongly prevented P. aeruginosa biofilm formation [69].…”

“…In addition, both hBNP and hCNP at 0.1 µM strongly prevented P. aeruginosa biofilm formation [69]. The most active peptide was hCNP, which was able to impair biofilm formation in a dose-dependent manner, and which was still able at 10 nM to reduce by a half the biofilm formation by P. aeruginosa [68]. …”

“…It was recently shown that the CNP concentration used to affect P. aeruginosa physiology is important, since CNP at 1 µM induced both specific effects through the AmiC sensor and nonspecific effects likely through its interaction with the bacterial membranes, triggering virulence and/or antibiofilm activities [68] (Fig. 1).…”

“…1). Conversely, CNP concentrations of 0.1 µM or less inhibited biofilm formation via binding to AmiC without an apparent virulence increase [68]. These data suggest that CNP or CNP derivatives could become interesting drugs for inhibition of P. aeruginosa biofilm formation either alone or in association with antibiotics, provided that a low hormone concentration is used.…”