Abstract
Chloroquine (CQ) is mainly known for antimalarial activity but due to lower sensitivity, it has not been well explored in the microbial disease treatment. In the present investigation, we attempted to enhance the CQ sensitivity in Pseudomonas aeruginosa. Presence of efflux pump is well demonstrated in bacterial system which plays an important role in drug sensitivity and resistance in bacteria and also serves other functions. Taking the advantage of presence of efflux pump in Pseudomonas aeruginosa, we made an attempt to sensitize the Pseudomonas aeruginosa with various plant extracts and phytochemicals for the development of CQ sensitivity. Ten rationally selected plant extracts were screened for the development of chloroquine sensitivity in P. aeruginosa. The chloroquine susceptibility assay was demonstrated by combining CQ and verapamil (a known efflux pump inhibitor) as a standard in an in vitro assay system. Results were quite encouraging as methanolic extracts of Syzygium aromaticum, Zingiber officinale and Curcuma longa were able to enhance chloroquine sensitivity in P. aeruginosa by increasing the zone of inhibition in well-defined assay system. These plant extracts were finally analysed for the presence of various phytochemicals. The Syzygium aromaticum extract showed the presence of phytochemicals, such as quinones, phenol, triterpenoid, saponins, tannins, alkaloids and flavonoids. On the other hand, the methanolic extract of Zingiber officinale and Curcuma longa showed the presence of saponins, tannins, alkaloids and flavonoids in the extract. Towards the identification of active principle of selected plant extract for CQ sensitivity enhancement, thin-layer chromatography was performed and various phytocomponent bands were isolated. Flavonoid (Rf 0.44) in Syzygium aromaticum, alkaloid (Rf 0.43) in Zingiber officinale and phenol (Rf 0.62) in Curcuma longa were found responsible for the enhancement of CQ susceptibility in P. aeruginosa. This interesting finding confirmed the concept that a prior course or combination of plant extracts or phytochemicals with chloroquine can be effective against P. aeruginosa. Present investigation successfully presented the proof of concept for the enhancement of chloroquine sensitivity in bacterial system by modulating an efflux pump. Concept can be explored for repurposing chloroquine for new applications.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13205-022-03382-1.
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