FUSIDIC ACID-RESISTANT MUTANTS DEFINE 3 REGIONS IN ELONGATION-FACTOR-G OF SALMONELLA-TYPHIMURIUM

We have sequenced fusA, the gene coding for elongation factor G (EF-G) , in 18 different mutants of Salmonella typhimurium selected as fusidi c acid resistant (FUR). In addition, we have sequenced two previously described FUR mutants from Escherichia coli. In all cases, the resista nce is due to a mutation in one of three separate regions in fusA. The three clusters of mutant sites superimpose on regions that are well c onserved, suggesting that they are of a more general functional import ance. To further classify the mutants, we have measured the minimal in hibitory concentration (MIC) for Fu and for two other antibiotics whic h interfere with translocation on the ribosome, kanamycin (Km) and spe ctinomycin (Sp). The levels of resistance to Fu for each of the mutant s are significantly higher than in the wild type (wt), and vary by abo ut one order of magnitude between the highest and the lowest. Most of the mutants are also more resistant to Km than the wt, although the le vel of resistance is low and the variation small. In contrast, about h alf of the mutants are more sensitive to Sp than the wt, with only one being more resistant. Only three of the twenty mutants behave like th e wt with respect to the non-selected phenotypes, Km(R) and Sp(R).