Assessment of the efficacy of an antimicrobial peptide in the context of cystic fibrosis airways

Abstract

Antimicrobial peptides (AMPs) offer a promising alternative to control airway infections with multi-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), which commonly infects patients with cystic fibrosis (CF). However, the behavior of AMPs in the CF context has yet to be fully elucidated. CF airways produce large amounts of proteases and viscous mucus (sputum), which may affect the efficacy of AMPs. The present work aimed to determine whether CF conditions affect the bactericidal efficacy of CAMA, a promising AMP known to kill clinical MRSA strains efficiently. Using a killing assay, we quantified CAMA bactericidal activity on a CF clinical MRSA strain in the presence of several compounds of CF airways, including sputum and bronchial epithelial cells (BECs). Our results indicate that CF sputum impairs the bactericidal efficacy of CAMA. Similar results were observed when CAMA was incubated with an artificial sputum medium (ASM). When used separately, sputum components (DNA, lipids, and mucins) reproduced the inhibitory effects of ASM. Additionally, the bactericidal efficacy of CAMA was also slightly altered when planktonic S. aureus strains were co-cultured with CF BECs. However, CAMA was not active against S. aureus cultured on BEC in biofilm mode, characteristic of chronic infections in CF patients. These findings suggest that although CAMA represents a promising tool to treat MRSA strains, the CF environment may impair the efficacy of this AMP. Identifying strategies to protect AMPs from the deleterious effects of CF sputum is a key priority.