Mechanisms of the dual effect of CHE in potentiating colistin efficacy and inhibiting the conjugative transfer of mcr-1-carrying IncI2 plasmids. (IMAGE)
Caption
(a) Without CHE, the LPS is modified by MCR-1, and colistin is expelled by efflux pumps, where it is difficult for colistin to disrupt the membrane structure. (b) CHE is able to penetrate into the phospholipid bilayers of the plasma membrane and increase the fluidity of the membrane, which inhibits the cellular respiration, disrupts the PMF, and generates ROS, leading to intracellular ATP depletion. (c) Since ATP is critically important, the function of mcr-1 is limited and the ratio of modified lipid A declines; the function of the efflux pumps is also impaired, which reverses the colistin resistant phenotype. (d) The ATP level is decreased by CHE and the genes involved in the conjugation bioprocess are downregulated, leading to a lower conjugation rate.
Credit
Huangwei Song et al.
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