Mode of action of the 2-phenylquinoline efflux inhibitor PQQ4R against Escherichia coli

PeerJ
Diana MachadoMiguel Viveiros

Abstract

Efflux pump inhibitors are of great interest since their use as adjuvants of bacterial chemotherapy can increase the intracellular concentrations of the antibiotics and assist in the battle against the rising of antibiotic-resistant bacteria. In this work, we have described the mode of action of the 2-phenylquinoline efflux inhibitor (4-(2-(piperazin-1-yl)ethoxy)-2-(4-propoxyphenyl) quinolone - PQQ4R), against Escherichia coli, by studding its efflux inhibitory ability, its synergistic activity in combination with antibiotics, and compared its effects with the inhibitors phenyl-arginine-β-naphthylamide (PAβN) and chlorpromazine (CPZ). The results showed that PQQ4R acts synergistically, in a concentration dependent manner, with antibiotics known to be subject to efflux in E. coli reducing their MIC in correlation with the inhibition of their efflux. Real-time fluorometry assays demonstrated that PQQ4R at sub-inhibitory concentrations promote the intracellular accumulation of ethidium bromide inhibiting its efflux similarly to PAβN or CPZ, well-known and described efflux pump inhibitors for Gram-negative bacteria and whose clinical usage is limited by their levels of toxicity at clinical and bacteriological effective concentratio...Continue Reading

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Apr 21, 2019·Medicinal Research Reviews·Andraž LamutTihomir Tomašič
Dec 2, 2017·Protein Science : a Publication of the Protein Society·Xuejun C ZhangJie Heng
Oct 23, 2019·Frontiers in Microbiology·Emily E WhittleJessica M A Blair
May 16, 2021·Applied and Environmental Microbiology·Nisha MaheyHemraj Nandanwar

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Methods Mentioned

BETA
density gradient centrifugation
Assay

Software Mentioned

Graph Pad
ECanything
GraphPad Prism
GraphPad

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