Resistin-like molecule beta, a colonic epithelial protein, exhibits antimicrobial activity against Staphylococcus aureus including methicillin-resistant strains.

ABSTRACT

PURPOSE: Resistin-like molecule beta (RELMß) is a small cysteine-rich protein secreted by colonic epithelial cells. RELMß mRNA and protein expressions are dramatically induced by bacterial exposure in germ-free mice. We hypothesized that RELMß has antimicrobial activity. METHODS: The antimicrobial activity of RELMß was screened by an agar spot test and confirmed by a liquid broth test. The amount of RELMß in human stools was semi-quantified by Western blot analysis. The induction of RELMß mRNA and protein expression by bacteria was measured by quantitative RT-PCR using LS174T cells. Electron microscopic immunohistochemistry was performed using polyclonal anti-RELMß antibody. RESULTS: RELMß showed antimicrobial activity against S. aureus and all MRSAs examined in a dose- and pH-dependent fashion. Western blot study showed that the amount of RELMß in healthy human stools was comparable to that exhibiting antimicrobial activity in vitro. Both RELMß mRNA and protein expression were induced by heat-inactivated S. aureus, but not by E. coli in LS174T cells. Electron microscopic immunohistochemistry showed that RELMß bound to the cell surface of S. aureus, followed by destruction of the bacterial cytoplasm. CONCLUSIONS: RELMß is a colonic antimicrobial protein and its antibacterial activity is species selective. Because RELMß is abundant in healthy human stool, RELMß may modulate gut flora.