Modified Defensins and Their Use

The ubiquitous use of antibiotics has resulted in the selection of bacteria that are relatively resistant to these drugs. Furthermore, few drugs are effective against viral and fungal microorganisms. There is therefore a continuing need to identify novel agents that reduce or inhibit the growth of such microorganisms, or to identify ways of modifying existing agents in order to give them superior antimicrobial activities, or to identify agents that may recruit inflammatory cells.

Defensins are broad-spectrum antimicrobial molecules that act against infectious agents and play important roles in the innate immune defense in vertebrates. These molecules exhibit a wide range of antimicrobial activities, including cytotoxicity towards bacteria cells, but are also cytotoxic for mammalian cells, which limits their usefulness as antimicrobial agents. The NIH announces the creation of modified defensins through their arginine residues. These compounds can be used to inhibit the toxic effect of defensins, while retaining their T cell chemotactic properties and promoting recruitment of inflammatory cells. In the case of pulmonary disease, these agents can be delivered directly to the site of inflammation by inhalation.