Differential Modulation of Intracellular Survival of Cytosolic and Vacuolar Pathogens by Curcumin

Abstract

ABSTRACTCurcumin, a principal component of turmeric, acts as an immunomodulator regulating the host defenses in response to a diseased condition. The role of curcumin in controlling certain infectious diseases is highly controversial. It is known to alleviate symptoms ofHelicobacter pyloriinfection and exacerbate that ofLeishmaniainfection. We have evaluated the role of curcumin in modulating the fate of various intracellular bacterial pathogens. We show that pretreatment of macrophages with curcumin attenuates the infections caused byShigella flexneri(clinical isolates) andListeria monocytogenesand aggravates those caused bySalmonella entericaserovar Typhi CT18 (a clinical isolate),Salmonella entericaserovar Typhimurium,Staphylococcus aureus, andYersinia enterocolitica. Thus, the antimicrobial nature of curcumin is not a general phenomenon. It modulated the intracellular survival of cytosolic (S. flexneriandL. monocytogenes) and vacuolar (Salmonellaspp.,Y. enterocolitica, andS. aureus) bacteria in distinct ways. Through colocalization experiments, we demonstrated that curcumin prevented the active phagosomal escape of cytosolic pathogens and enhanced the active inhibition of lysosomal fusion by vacuolar pathogens. A chloroquine resistance assay confirmed that curcumin retarded the escape of the cytosolic pathogens, thus reducing their inter- and intracellular spread. We have demonstrated that the membrane-stabilizing activity of curcumin is crucial for its differential effect on the virulence of the bacteria.