Inhibition of Lipopolysaccharide Activity by a Bacterial Cyclic Lipopeptide Surfactin

Abstract

Compounds that inactivate lipopolysaccharide (LPS) activity have the potential of being new antiinflammatory agents. Therefore, we searched among microbial secondary metabolites for compounds that inhibited LPS-stimulated adhesion between human umbilical vein endothelial cells (HUVEC) and HL-60 cells. By this screening, we found a cyclic lipopeptide surfactin from the culture broth of Bacillus sp. BML752-121F2 to be inhibitory. The addition of the surfactin prior to the LPS stimulation decreased HL-60 cell-HUVEC adhesion without showing any cytotoxicity. We confirmed that surfactin inhibited LPS-induced expression of ICAM-1 and VCAM-1 in HUVEC. It also inhibited the cellular adhesion induced by lipid A, the active component of LPS; but it did not inhibit TNF-a or IL-1b -induced cell adhesion. Then, surfactin was shown to suppress the interaction of lipid A with LPS-binding protein (LBP) that mediates the transport of LPS to its receptors. Finally, surface plasmon resonance (SPR) analysis revealed the surfactin to interact reversibly with lipid A. Thus, this Bacillus surfactin was shown to be an inhibitor of LPS-induced signal transduction, directly interacting with LPS.

Surfactin - Novel Solutions for Global Issues

“…Surfactin was shown to suppress the interaction of lipid A with LPS-binding protein (LBP) that mediates the transport of LPS to its receptors. Moreover, surfactin did not influence the viability of the eukaryotic cell lines tested (Takahashi et al, 2006). Surfactin also inhibits the LPS-induced expression of inflammatory mediators (IL-1ǐ and iNOS) and reduces the plasma endotoxin, TNF-Ǐ and nitric oxide levels in response to septic shock in rats (Hwang et al, 2007).…”

“…No surfactin-related toxicities in survival, clinical signs, haematological parameters and histopathological observations of haematopoietic organs were found (Hwang et al, 2009). Surfactin did not influence the viability of HUVEC (human umbilical vein endothelial cells) up to 30 µg/ml after 24 h. Surfactin was also regarded as being less toxic than other surfactants, as judged from the results of an acute toxicity study in mice (Takahashi et al, 2006) and also as a safer anti-endotoxin agent in comparison with polymyxin B (Hwang et al, 2007). Another option for reducing surfactin toxicity is to design a tailor-made molecule.…”

Review of surfactin chemical properties and the potential biomedical applications

“…Surfactin did not influence the viability of HUVEC (human umbilical vein endothelial cells) up to 30 µg/ml after 24 hours. Surfactin was also regarded less toxic than other surfactants as judged from the results of an acute toxicity study in mice [69] and also as a safer anti-endotoxin agent in comparison with polymyxin B [68].…”

“…Surfactin was also shown to suppress the interaction of lipid A with LPS-binding protein (LBP) that mediates the transport of LPS to its receptors. Moreover, surfactin did not influence the viability of the tested eukaryotic cell lines [69].…”

A New Antifungal Cyclic Lipopeptide from Bacillus marinus B‐9987

“…1) determined based on the chemical analysis and all kinds of spectroscopic methods. Cyclic lipopeptides exhibit biological activities such as antifungal [7], antitumor [8], and antiinflammatory [9] properties. Here, we describe the isolation, structural elucidation, and antifungal bioassay of the new cyclic lipopeptide and three known cyclodipeptides.…”