SignificanceAntibiotic tolerance causes antibiotic treatment failure and promotes the emergence of genotypic resistance in chronic infections, such as those caused by the pathogen Pseudomonas aeruginosa. Laboratory stationary-phase bacteria exhibit a slow growing and metabolically quiescent state associated with high levels of multidrug tolerance likely analogous to the in vivo environment during chronic infection. We demonstrate that superoxide dismutases confer multidrug tolerance in stationary-phase bacteria, and identify a link between (p)ppGpp-mediated stress responses, superoxide metabolism, and membrane permeability to antibiotics. Inhibition of superoxide dismutase activity may overcome multidrug tolerance and potentiate current bactericidal antibiotics in the treatment of P. aeruginosa chronic infections.

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Saccharomyces species have five TPO genes, TPO1 through TPO5, coding for proteins that are involved in up taking or excreting intracellular spermine, putrescine or spermidine. Here, we investigate the evolutionary fate and functional impacts of gene conversions between these genes. Our results show that gene conversions occurred only between the TPO2 and TPO3 genes of the six Saccharomyces species we studied. They also show that these gene conversions occurred independently in all six species. The facts that they only occur between closely related genes having similar function, and that they are limited to the transmembrane domain of these proteins, suggest that they have little functional impact. These gene conversions therefore likely represent neutral mutations which are not subject to purifying selection.