Antimicrobial activity of murine lung cells against Staphylococcus aureus is increased in vitro and in vivo after elafin gene transfer.

Staphylococcus aureus is a pathogen often found in pneumonia and sepsis. In the context of the resistance of this organism to conventional antibiotics, an understanding of the regulation of natural endogenous antimicrobial molecules is of paramount importance. Previous studies have shown that both human and mouse airways express a variety of these molecules, including defensins, cathelicidins, and the four-disulfide core protein secretory leukocyte protease inhibitor. We demonstrate here by culturing mouse tracheal epithelial cells at an air-liquid interface that, despite the production of Defb1, Defb14, and Defr1 in this system, these cells are unable to clear S. aureus when exposed to this respiratory pathogen. Using an adenovirus (Ad)-mediated gene transfer strategy, we show that overexpression of elafin, an anti-elastase/antimicrobial molecule (also a member of the four-disulfide core protein family), dramatically improves the clearance of S. aureus. In addition, we also demonstrate that this overexpression is efficient in vivo and that intratracheal instillation of Ad-elafin significantly reduced the lung bacterial load and demonstrates concomitant anti-inflammatory activity by reducing neutrophil numbers and markers of lung inflammation, such as bronchoalveolar lavage levels of tumor necrosis factor and myeloperoxidase. These findings show that an increased antimicrobial activity phenotype is provided by the elafin molecule and have implications for its use in S. aureus-associated local and systemic infections.

Society for general microbiology - 148th ordinary meeting. Activities and actions of antimicrobial peptides. 26-30 March 2001, Edinburgh, UK.

The rapidly expanding field of antimicrobial peptides is one that is attracting increasing interest from research groups around the world. The importance of antimicrobial agents in providing alternatives to conventional antibiotics has been highlighted in recent years by the emergence of a number of multidrug-resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Indeed, bacteria refractory to treatment by all known antibiotics are now a reality and the need for developing novel antimicrobial agents is urgent. This meeting brought together researchers working in a number of varied, but ultimately related areas. The functional diversity and putative mechanisms of action of antimicrobial peptides were discussed in depth, along with recent developments in the design of synthetic peptides with enhanced antimicrobial properties. Several ongoing studies were described, ranging from research into cystic fibrosis to work in the food industry. It was emphasized that cationic antimicrobial peptides have a range of properties to offer the world of scientific research and may play an important role in the ongoing battle against pathogenic microorganisms. Oral presentation sessions of the conference were co-chaired by Dr Deirdre A Devine (University of Leeds, UK) and Dr David G Smith (University of Edinburgh, UK).