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Ursolic acid inhibits colistin efflux and curtails colistin resistant Enterobacteriaceae

dc.contributor.authorSundaramoorthy, Niranjana S
dc.contributor.authorMohan, Harihar M
dc.contributor.authorSubramaniam, Shankar
dc.contributor.authorRaman, Thiagarajan
dc.contributor.authorSelva Ganesan, Subramaniapillai
dc.contributor.authorSivasubamanian, Aravind
dc.contributor.authorNagarajan, Saisubramanian
dc.date.accessioned2019-02-24T04:20:05Z
dc.date.available2019-02-24T04:20:05Z
dc.date.issued2019-02-18
dc.identifier.citationAMB Express. 2019 Feb 18;9(1):27
dc.identifier.urihttps://doi.org/10.1186/s13568-019-0750-4
dc.identifier.urihttps://hdl.handle.net/2027.42/148135
dc.description.abstractAbstract Colistin resistance in Enterobacteriaceae especially Klebsiella pneumoniae and Escherichia coli is driving the evolution of pan drug resistant strains. Screening a library of 13 plant nutraceuticals led to the identification of acetyl shikonin and ursolic acid, which exhibited synergy with colistin against extremely drug resistant (XDR) clinical strains of E. coli (U3790) and K. pneumoniae (BC936). Ursolic acid caused a significant colistin MIC reversal of 16-fold in U3790 and 4-fold in BC936 strains. Ursolic acid also potentiated the bactericidal effect of colistin against both U3790 and BC936 by causing ~ 4 to 4.5 log fold decline in CFU of both clinical isolates in a time kill assay. At 2× minimum effective concentration, ursolic acid was non-toxic to zebrafish as evidenced by brain and liver enzyme profiles and by histopathology studies. In combination with colistin, ursolic acid reduced bacterial bioburden of U3790/BC936 by 1–1.58 log fold from the infected muscle tissue of zebrafish. Mechanistic explorations via studies on real time efflux, membrane potential and intracellular accumulation of dansyl chloride tagged colistin revealed that colistin efflux is inhibited by ursolic acid. In addition, ursolic acid also enhanced outer membrane permeability which probably facilitates colistin’s attack on outer and inner membranes. Our study shows that ursolic acid synergizes with colistin by inhibiting colistin efflux in Enterobacteriaceae that helps to curtail colistin resistant Enterobacteriaceae.
dc.titleUrsolic acid inhibits colistin efflux and curtails colistin resistant Enterobacteriaceae
dc.typeArticleen_US
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/148135/1/13568_2019_Article_750.pdf
dc.language.rfc3066en
dc.rights.holderThe Author(s)
dc.date.updated2019-02-24T04:20:06Z
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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