Lipid transfer protein isolated from noni seeds displays antibacterial activity in vitro and improves survival in lethal sepsis induced by CLP in mice

Abstract

In the present study, we aimed to evaluate the antibacterial activity of a lipid transfer protein isolated from Morinda citrifolia L. seeds, named McLTP₁, and to investigate its effect in the cecal ligation and puncture (CLP) mouse sepsis model. Antimicrobial assays revealed that McLTP₁ (12.5-800 μg/mL) significantly reduced Staphylococcus aureus (ATCC 6538P and ATCC 14458) and Staphylococcus epidermidis (ATCC 12228) planktonic growth, reaching maximal inhibition of approximately 50% and 98%, respectively. Furthermore, McLTP₁ inhibited biofilm formation of both S. aureus strains, achieving percentages ranging from 39.1% to 69.1% (200-800 μg/mL) for ATCC 6538P and 34.4%-63% (12.5-800 μg/mL) for ATCC 14458. A synergistic interaction between McLTP₁ and oxacillin against S. aureus and S. epidermidis was also observed, as determined by fractional inhibitory concentration indices of 0.18 and 0.38, respectively. McLTP₁ showed no significant inhibitory effect against Gram-negative bacteria. In the in vivo experiments, sepsis was lethal to 83% of the animals, 72 h after CLP. In contrast, 100% of the animals treated with McLTP₁ (8 mg/kg) before (intraperitoneal injection or oral dose) or after (oral dose) CLP were still alive 3 days later. In addition, oral or intraperitoneal administration of McLTP₁ (8 mg/kg) significantly reduced the body weight loss, fever, leukocytosis, organ damage, and the level of inflammatory serum cytokines induced by sepsis. In conclusion, McLTP₁ could be exploited for its antimicrobial properties, and can be considered a potential therapeutic candidate for the management of clinical sepsis.

Keywords: Antimicrobial activity; Lipid transfer protein; Morinda citrifolia L.; Sepsis.