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Analysis of Mupirocin Resistance and Fitness in Staphylococcus aureus by Molecular Genetic and Structural Modeling Techniques. Julian Gregston Hurdle, 2004.Chromosomal resistance to mupirocin in clinical isolates of Staphylococcus aureus arises from V588F or V631F mutations in isoleucyl-tRNA synthetase (IRS) . Whether these are the only IRS mutations that confer mupirocin resistance or simply those that survive in the clinic is unknown . Mupirocin-resistant mutants of S . aureus 8325-4 were therefore generated to examine their ileS genotypes and the in vitro and in vivo fitness costs associated with them before and after compensatory evolution . Most spontaneous first-step mupirocin-resistant mutants carried V588F or V631F mutations in IRS, but a new mutation (G593V) was also identified . Second-step mutants carried combinations of previously identified IRS mutations (e.g., V588F/V631F and G593V/V631F), but additional combinations also occurred involving novel mutations (R816C, H67Q, and F563L) . First-step mupirocin-resistant mutants were not associated with substantial fitness costs, a finding that is consistent with the occurrence of V588F or V631F mutations in the IRS of clinical strains . Second-step mutants were unfit, but fitness could be restored by subculture in the absence of mupirocin . In most cases, this was the result of compensatory mutations that also suppressed mupirocin resistance (e.g., A196V, E190K, and E195K), despite retention of the original mutations conferring resistance . Structural explanations for mupirocin resistance and loss of fitness were obtained by molecular modeling of mutated IRS enzymes, which provided data on mupirocin binding and interaction with the isoleucyl-AMP reactive intermediate . Glycine Betaine Transmethylase Mutant of Pseudomonas aeruginosa. Ana L. Serra, 2002.The gene for glycine betaine transmethylase (gbt) was identified in Pseudomonas aeruginosa strain Fildes III by biochemical, physiological, and molecular approaches . Based on sequence analysis, the knockout gene corresponded to an open reading frame (ORF) named PA3082 in the genome of P . aeruginosa PAO1 . The translated product of this ORF displayed similarity to transferases of different microorganisms . Mutation in gbt blocked the utilization of choline and glycine betaine as carbon and nitrogen sources . Biochemical Function of msl5 (pks8 plus pks17) in Mycobacterium tuberculosis H37Rv: Biosynthesis of Monomethyl Branched Unsaturated Fatty Acids. Vinod S. Dubey, 2003.We show that the disruption of one of the mycocerosic acid synthase (mas)-like genes, msl5 (pks8 plus pks17) in Mycobacterium tuberculosis H37Rv generates a mutant incapable of producing monomethyl branched unsaturated C16 to C20 fatty acids that are minor constituents of acyltrehaloses and sulfolipids . The msl5 mutation did not cause any significant change in the acyl lipid composition and also did not affect growth in culture, in mouse alveolar macrophage cell line MH-S, or in the murine lung .
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