BACTERIAL-RESISTANCE TO UNCOUPLERS

Uncoupler resistance presents a potential challenge to the conventiona l chemiosmotic coupling mechanism. In E. coli, an adaptive response to uncouplers was found in cell growing under conditions requiring oxida tive phosphorylation. It is suggested that uncoupler-resistant mutants described in the earlier literature might represent a constitutive st ate of expression of this ''low energy shock'' adaptive response. In t he environment, bacteria are confronted by nonclassical uncoupling fac tors such as organic solvents, heat, and extremes of pH. It is suggest ed that the low energy shock response will aid the cell in coping with the effects of natural uncoupling factors. The genetic analysis of un coupler resistance has only recently began, and is yielding interestin g and largely unexpected results. In Bacillus subtilis, a mutation in fatty acid desaturase causes an increased content of saturated fatty a cids in the membrane and increased uncoupler resistance. The protonoph oric efficiency of uncouplers remains unchanged in the mutants, inviti ng nonorthodox interpretations of the mechanism of resistance. In E. c oli, two loci conferring resistance to CCCP and TSA were cloned and we re found to encode multidrug resistance pumps. Resistance to one of th e uncouplers, TTFB, remained unchanged in strains mutated for the MDRs , suggesting a resistance mechanism different from uncoupler extrusion .