Abstract
Cystic fibrosis (CF) is characterized by recurrent airway infections with antibiotic-resistant bacteria and chronic inflammation. Chicken cathelicin-2 (CATH-2) has been shown to exhibit antimicrobial activity against antibiotic-resistant bacteria and to reduce inflammation. In addition, exogenous pulmonary surfactant has been suggested to enhance pulmonary drug delivery. It was hypothesized that CATH-2 when combined with an exogenous surfactant delivery vehicle, bovine lipid extract surfactant (BLES), would exhibit antimicrobial activity against CF-derived bacteria and downregulate inflammation. Twelve strains of CF-pathogens were exposed to BLES+CATH-2 in vitro and killing curves were obtained to determine bactericidal activity. Secondly, heat-killed bacteria were administered in vivo to elicit a pro-inflammatory response with either a co-administration or delayed administration of BLES+CATH-2 to assess the antimicrobial-independent, anti-inflammatory properties of BLES+CATH-2. CATH-2 alone exhibited potent antimicrobial activity against all clinical strains of antibiotic-resistant bacteria, while BLES+CATH-2 demonstrated a reduction, but significant antimicrobial activity against bacterial isolates. Furthermore, BLES+CATH-2 reduced inflammation in vivo when either co-administered with killed bacteria or after delayed administration. The use of a host-defense peptide combined with an exogenous surfactant compound, BLES+CATH-2, is shown to exhibit antimicrobial activity against antibiotic-resistant CF bacterial isolates and reduce inflammation.
Highlights
Meropenem R; Ciprofloxacin, Gentamicin I cell injury and airway remodelling[6,7,8,9,10,11,12] and results in greater challenge from a therapeutic standpoint
It was hypothesized that bovine lipid-extract surfactant (BLES)+CATH-2 would exhibit potent bactericidal activity against bacterial isolates obtained from Cystic fibrosis (CF) patients and, could reduce inflammation associated with bacterial killing in vivo
The antimicrobial and anti-inflammatory effects of BLES+CATH-2, a chicken cathelicidin suspended in a clinical exogenous surfactant preparation, BLES, were evaluated for therapeutic potential as a novel treatment for antibiotic-resistant bacterial lung infections
Summary
Meropenem R; Ciprofloxacin, Gentamicin I cell injury and airway remodelling[6,7,8,9,10,11,12] and results in greater challenge from a therapeutic standpoint. Exogenous cathelicidins are a class of innate host-defense peptides that are currently under investigation for their potential therapeutic use against antibiotic-resistant bacterial infections and have been shown to possess both direct antibacterial activity and immunomodulatory activity. Based on their multiple mechanism of action, these host defense peptides are notable for their antimicrobial activity against a wide spectrum of bacteria that exhibit resistance to conventional antibiotics and represent an attractive target for therapeutic development[13,14,15,16]. It was hypothesized that BLES+CATH-2 would exhibit potent bactericidal activity against bacterial isolates obtained from CF patients and, could reduce inflammation associated with bacterial killing in vivo
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