Peptides derived from the human laminin a4 and a5 chains exhibit antimicrobial activity

Laminins are a family of heterotrimeric extracellular matrix glycoproteins in the basement membrane of different tissues and are composed of a, b, and g chains. In mammals, five different a chains, three b chains, and three g chains have been identified that assemble into 15 different laminins. Each a-chain possesses a C-terminal globular domain which can be subdivided into the five subdomains LG1-LG5. LG1-LG3 modules are connected to LG4-LG5 by a linker domain which is known to be sensitive to proteolytic processing. Here, we show that peptides derived from the human laminin a4 and a5 chain, exhibit a dose-dependent antimicrobial activity against gram-positive and gram-negative bacteria. Furthermore, we show that these peptides permeabilize the bacterial membrane and are able to bind to bacterial DNA. Interestingly, the ability to kill the microorganisms correlated with their ability to bind to heparin. These data suggest that extracellular matrix components are able to protect the respective tissues from invading pathogens and are part of the host defense response.