Piperine and Tabersonine, but Not Lupinine, Inhibit S. proteamaculans Invasion of M-HeLa Cells

The pathogenesis of a bacterial infection is a multistep process typically involving bacterial attachment to the host, toxin production, and/or invasion, followed by inflammation. For many bacteria, the invasion of human cells is a key step in the spread of infection and evasion of host immunity. Fusion of host cell membranes during bacterial penetration is a necessary step in invasion. The aim of this study was to evaluate the plant alkaloids, such as piperine, tabersonine, and lupinine, which have the potential to inhibit membrane fusion, fighting bacterial infection. Despite previous data on lupinine's inhibition of membrane fusion, it has no effect on invasion or on the synthesis of the proinflammatory cytokines. This was likely due to the synthesis of the surface protein OmpX, which was a virulence factor for <i>S. proteamaculans</i> and can neutralize the effect of lupinine on the host cell membrane. Piperine and tabersonine inhibit invasion and proinflammatory cytokine synthesis in response to bacterial infection. However, tabersonine is toxic to eukaryotic cells. This makes it necessary to select an optimal concentration of tabersonine that suppresses invasion but is nontoxic to human cells. Therefore, piperine holds the greatest prospects for clinical use: it inhibits bacterial invasion while remaining nontoxic to human cells even at higher concentrations.