Jouault Albane, Jeguirim Inès, Kaddour Inès Ben Hadj, Touqui Lhousseine
Institut Pasteur, Université de Paris Cité, Mucoviscidose et Bronchopathies Chroniques, Paris, France.
Centre de Recherche Saint-Antoine, Sorbonne Université, Inserm, Paris, France.
Curr Res Microb Sci. 2025 Feb 28;8:100367. doi: 10.1016/j.crmicr.2025.100367. eCollection 2025.
Antimicrobial peptides (AMPs) offer a promising alternative to control airway infections with multi-resistant bacteria, such as methicillin-resistant (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 strains were co-cultured with CF BECs. However, CAMA was not active against 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.
抗菌肽（AMPs）为控制由多重耐药细菌引起的气道感染提供了一种有前景的替代方法，比如耐甲氧西林金黄色葡萄球菌（MRSA），这种细菌通常感染囊性纤维化（CF）患者。然而，AMPs在CF环境中的行为尚未完全阐明。CF气道会产生大量蛋白酶和粘性黏液（痰液），这可能会影响AMPs的疗效。目前的研究旨在确定CF环境是否会影响CAMA的杀菌效果，CAMA是一种已知能有效杀死临床MRSA菌株的有前景的AMPs。我们使用杀伤试验，在存在几种CF气道成分（包括痰液和支气管上皮细胞（BECs））的情况下，对CF临床MRSA菌株上的CAMA杀菌活性进行了量化。我们的结果表明，CF痰液会削弱CAMA的杀菌效果。当CAMA与人工痰液培养基（ASM）一起孵育时，也观察到了类似的结果。当单独使用时，痰液成分（DNA、脂质和粘蛋白）重现了ASM的抑制作用。此外，当浮游菌株与CF BECs共培养时，CAMA的杀菌效果也略有改变。然而，CAMA对以生物膜模式在BEC上培养的细菌没有活性，而生物膜模式是CF患者慢性感染的特征。这些发现表明，尽管CAMA是治疗MRSA菌株的一种有前景的工具，但CF环境可能会削弱这种AMPs的疗效。确定保护AMPs免受CF痰液有害影响的策略是一个关键的优先事项。
