The cationic peptide magainin II is antimicrobial for Burkholderia cepacia-complex strains

Abstract

This study was undertaken to determine the antibacterial activity of eight cationic antimicrobial peptides towards strains of genomovars I-V of the Burkholderia cepacia complex (Bcc) in timekill assays. All but one of the peptides failed to show activity against the panel of test strains. The exception was magainin II, a 23 aa peptide isolated from the epidermis of the African clawed frog, Xenopus laevis, which exhibited significant bactericidal activity for Bcc genomovars most frequently associated with lung infection of patients with cystic fibrosis. In vitro studies indicated that magainin II protected a human bronchial epithelial cell line (BEAS-2B) from killing by Bcc and suggest that this peptide may have therapeutic potential against these organisms. INTRODUCTIONOrganisms of the Burkholderia cepacia complex (Bcc) are associated with chronic opportunistic lung infections of patients suffering from cystic fibrosis (CF) and chronic granulomatous disease (Mahenthiralingam et al., 2000). Infections with Bcc are often coupled with a particularly poor prognosis, resulting in a rapid and fatal decline in pulmonary function due to necrotizing pneumonia and sepsis (Isles et al., 1984). This fatal decline in clinical condition has been termed 'cepacia syndrome' and has not been identified with any other CF-associated pathogen.The Bcc comprises 15 distinct species formerly known as genomovars of B. cepacia (Vanlaere et al., 2008). Of these, the majority of infections in CF are attributed to Burkholderia multivorans and Burkholderia cenocepacia in both the UK and the USA Reik et al., 2005), although all genomovars have been recovered from CF patients (Ortega et al., 2005). Eradication of an established Bcc infection is rarely achieved owing to the high intrinsic resistance of the genus to antimicrobial agents (Coenye et al., 2001). Although preventative strategies are considered the principal approach for management of Bcc infections (Jones & Webb, 2003), combination therapy may be used, extending the spectrum of antimicrobial activity across multiple antibiotic classes (Bonacorsi et al., 1999).Novel antimicrobial therapeutic agents are urgently required due to the threat of naturally resistant and antibiotic-resistant strains. Cationic antimicrobial peptides (CAMPs) have potential, as they show broad-range activity against Gram-positive and Gram-negative bacteria, viruses and some fungal species (Hancock & Lehrer, 1998). Importantly, these peptides do not present the same issue of resistance observed with conventional antibiotics (Zasloff, 2002) and often have good activity against several multidrug-resistant bacterial species (Giacometti et al., 2005a). There is also evidence that in vitro selection of CAMP-resistant mutants is difficult (Hancock & Lehrer, 1998). As previous reports have described B. cepacia as being resistant to the action of CAMPs (Denyer & Maillard, 2002;Scott et al., 1999), we aimed to determine the efficacy of a panel of antimicrobial peptides against B. cepacia from genomovars I-V. METHODSBact...

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