Effect of loperamide on transcriptional profile of Raw264.7 cells infected with Salmonella

Our previous screening allowed us to identify the loperamide (LPD) as a potent inhibitor of S. Typhimurium intracellular proliferation. LPD treatment of infected cells markedly promoted the host autophagic response and lysosomal activity. A mechanistic study revealed that the elevated host autophagy and elimination of intracellular bacteria were dependent on the high expression of glycoprotein nonmetastatic melanoma protein B (GPNMB) induced by LPD. In addition, LPD treatment could effectively protect S. Typhimurium-infected LPD Galleria mellonella and mouse models. Thus, our study suggests that LPD may be used for the treatment of diseases caused by intracellular bacterial pathogens. Moreover, LPD may serve as a promising lead compound for the development of anti-infection drugs based on the HDT strategy.