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.

Highlights

  • The biofilm lifestyle largely adopted by bacteria allows their protection against environmental stresses including those induced by biocides or antibiotics [1], leading to persistency and chronic infections [2]

  • Since virulence and biofilm formation are inversely regulated in P. aeruginosa, we naturally investigated the effect of natriuretic peptides, and more C-type Natriuretic Peptide (CNP), on P. aeruginosa biofilm formation

  • These results show that CNP impedes biofilm development of P. aeruginosa in a dose-dependent manner when tested in dynamic conditions

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Summary

Introduction

The biofilm lifestyle largely adopted by bacteria allows their protection against environmental stresses including those induced by biocides or antibiotics [1], leading to persistency and chronic infections [2]. Pathogens 2018, 7, 47 their high-speed reproduction, and adaptability, they progressively promoted a selection of the most resistant strains. This constitutes a new challenge for treating bacterial infections [4]. In this context, the principle of a bi-therapeutic approach, in which an anti-biofilm compound is used to restore the bacterial sensitivity to co-administrated antibiotics [5,6], constitutes a promising strategy to develop new anti-bacterial treatments [7]. If the principle is elegant, its application is not obvious as it has been observed that bacteria can develop resistances against anti-biofilm compounds, such as cationic antimicrobial peptides (CAMP) through activation of various sensors and transduction systems [8,9,10]

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