Curcumin reduces the antimicrobial activity of ciprofloxacin against Salmonella typhimurium and Salmonella typhi.
OBJECTIVE
Typhoidal and non-typhoidal infection by Salmonella is a serious threat to human health. Ciprofloxacin is the last drug of choice to clear the infection. Ciprofloxacin, a gyrase inhibitor, kills bacteria by inducing chromosome fragmentation, SOS response and reactive oxygen species (ROS) in the bacterial cell. Curcumin, an active ingredient from turmeric, is a major dietary molecule among Asians and possesses medicinal properties. Our research aimed at investigating whether curcumin modulates the action of ciprofloxacin.


METHODS
We investigated the role of curcumin in interfering with the antibacterial action of ciprofloxacin in vitro and in vivo. RT-PCR, DNA fragmentation and confocal microscopy were used to investigate the modulation of ciprofloxacin-induced SOS response, DNA damage and subsequent filamentation by curcumin. Chemiluminescence and nitroblue tetrazolium reduction assays were performed to assess the interference of curcumin with ciprofloxacin-induced ROS. DNA binding and cleavage assays were done to understand the rescue of ciprofloxacin-mediated gyrase inhibition by curcumin.


RESULTS
Curcumin interferes with the action of ciprofloxacin thereby increasing the proliferation of Salmonella Typhi and Salmonella Typhimurium in macrophages. In a murine model of typhoid fever, mice fed with curcumin had an increased bacterial burden in the reticuloendothelial system and succumbed to death faster. This was brought about by the inhibition of ciprofloxacin-mediated downstream signalling by curcumin.


CONCLUSIONS
The antioxidant property of curcumin is crucial in protecting Salmonella against the oxidative burst induced by ciprofloxacin or interferon γ (IFNγ), a pro-inflammatory cytokine. However, curcumin is unable to rescue ciprofloxacin-induced gyrase inhibition. Curcumin's ability to hinder the bactericidal action of ciprofloxacin and IFNγ might significantly augment Salmonella pathogenesis.
Department of Microbiology and Cell Biology, Centre for Infectious Disease Research and Biosafety Laboratories,  Indian Institute of Science, Bangalore 560012,  India.
Sandhya A
SA
Marathe
Rupesh
R
Kumar
Parthasarathi
P
Ajitkumar
Valakunja
V
Nagaraja
Dipshikha
D
Chakravortty
D000818:Animals; D000890:Anti-Infective Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology; D002939:Ciprofloxacin / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D003474:Curcumin / Q000494:pharmacology*; D004347:Drug Interactions / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D012480:Salmonella Infections / Q000188:drug therapy / Q000401:mortality; D012485:Salmonella typhi / Q000187:drug effects* / Q000254:growth & development; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000254:growth & development; D020298:U937 Cells
D000890:Anti-Infective Agents; D000975:Antioxidants; D002939:Ciprofloxacin; D003474:Curcumin