Genomic Insights into Solvent Tolerance and Pumps That Extrude Toxic Chemicals
María-Trinidad Gallegos, Antonio J. Molina-Henares, Xiaodong Zhang, Wilson Terán, Patricia Bernal, Yilmaz Alguel, María-Eugenia Guazzaroni, Tino Krell, Ana Segura and Juan-Luis Ramos
from: Microbial Biodegradation: Genomics and Molecular Biology (Edited by: Eduardo Díaz). Caister Academic Press, U.K. (2008)
Organic solvents are toxic for microorganisms because they dissolve in the cytoplasmic membranes, a process that alters the membrane's physical structure and renders the cell unable to synthesize ATP. The degree of toxicity varies depending on the chemical and the strain involved, and chemical toxicity correlates with the partition coefficient of the compound in a mixture of octanol and water. Microbial tolerance to solvents can be mediated by physical and biochemical barriers. Physical barriers are usually based on increased membrane rigidity through the alteration of the cis/trans unsaturated fatty acid ratio, the increase in the saturated:unsaturated fatty acid ratio, or alteration in the phopholipd head groups. Although these barriers counteract the effect of initial toxicity, long-term resistance is based on the active extrusion of solvents, which is mainly mediated by extrusion pumps. Genomic analyses in Gram-negative bacteria have revealed that the resistance-nodulation-cell division (RND) family of efflux pumps is the main group involved in the removal of solvents from the cell. These pumps are made up of three components that span the membranes and extrude solvents from the inner membrane or cytoplasm to the outer medium. The level of expression of these extrusion pumps is finely modulated by transcriptional regulators belonging to different families, but which act in a similar fashion. Some regulators act as repressors that prevent access of the RNA polymerase to the promoter region of the cognate operon. These regulators recognize multiple drugs through a series of overlapping binding pockets, and upon the binding of an effector, transmit a signal to the DNA binding region so that the regulator is released and the genes encoding the efflux pumps are transcribed read more ...