Differential modulation of intracellular survival of cytosolic and vacuolar pathogens by curcumin.
Curcumin, 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 of Helicobacter pylori infection and exacerbate that of Leishmania infection. 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 by Shigella flexneri (clinical isolates) and Listeria monocytogenes and aggravates those caused by Salmonella enterica serovar Typhi CT18 (a clinical isolate), Salmonella enterica serovar Typhimurium, Staphylococcus aureus, and Yersinia enterocolitica. Thus, the antimicrobial nature of curcumin is not a general phenomenon. It modulated the intracellular survival of cytosolic (S. flexneri and L. monocytogenes) and vacuolar (Salmonella spp., Y. enterocolitica, and S. 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.
Department of Microbiology and Cell Biology, Centre for Infectious Disease Research and Biosafety Laboratories, Indian Institute of Science, Bangalore, India.
Sandhya A
SA
Marathe
Minakshi
M
Sen
Ishani
I
Dasgupta
Dipshikha
D
Chakravortty
D000818:Animals; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000382:microbiology; D058507:Host Specificity; D054884:Host-Pathogen Interactions; D006801:Humans; D008089:Listeria monocytogenes / Q000187:drug effects* / Q000254:growth & development; D008247:Lysosomes / Q000187:drug effects / Q000382:microbiology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability / Q000187:drug effects; D010588:Phagosomes / Q000187:drug effects / Q000382:microbiology; D012485:Salmonella typhi / Q000187:drug effects* / Q000254:growth & development; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000254:growth & development; D012763:Shigella flexneri / Q000187:drug effects* / Q000254:growth & development; D013045:Species Specificity; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D014617:Vacuoles / Q000187:drug effects / Q000382:microbiology; D015008:Yersinia enterocolitica / Q000187:drug effects* / Q000254:growth & development
D003474:Curcumin