Human -Defensin 2 Induces Extracellular Accumulation of Adenosine in Escherichia coli

Human-defensins are host defense peptides performing antimicrobial as well as immunomodulatory functions. The present study investigated whether treatment of Escherichia coliwith human -defensin 2 could generate extracellular molecules of rele-vance for immune regulation. Mass spectrometry analysis of bacterial supernatants detected the accumulation of purine nucleo-sides triggered by-defensin 2 treatment. Other cationic antimicrobial peptides tested presented variable outcomes with regard to extracellular adenosine accumulation; human -defensin 2 was the most efficient at inducing this response. Structural and biochemical evidence indicated that a mechanism other than plain lysis was involved in the observed phenomenon. By use of isotope (13C) labeling, extracellular adenosine was found to be derived from preexistent RNA, and a direct interaction between the peptide and bacterial nucleic acid was documented for the first time for -defensin 2. Taken together, the data suggest that defensin activity on a bacterial target may alter local levels of adenosine, a well-known immunomodulator influencing inflam-matory processes. Human -defensins (hBD) are cationic antimicrobial peptidesproduced predominantly by epithelial cells (1). Notably, in the intestine, an environment populated by a dense and rich mi-crobial community, epithelial defensins reinforce the host innate defense (2). These peptides are normally expressed at low basal levels, but hBD-2 and-3 can be upregulated by a variety of micro