title: Biological cost of rifampin resistance from the perspective of Staphylococcus aureus.
abstract: Resistance determinants that interfere with normal physiological processes in the bacterial cell usually cause a reduction in biological fitness. Fitness assays revealed that 17 of 18 in vitro-selected chromosomal mutations within the rpoB gene accounting for rifampin resistance in Staphylococcus aureus were associated with a reduction in the level of fitness. There was no obvious correlation between the level of resistance to rifampin and the level of fitness loss caused by rpoB mutations. Among 23 clinical rifampin-resistant S. aureus isolates from six countries, only seven different rpoB genotypes could be identified, whereby the mutation 481His-->Asn was present in 21 (91%) of these 23 isolates. The mutation 481His-->Asn, in turn, which confers low-level rifampin resistance on its own, was not shown to be associated with a cost of resistance in vitro. The restriction to distinct mutations that confer rifampin resistance in vivo, as demonstrated here, appears to be determined by the Darwinian fitness of the organisms.
authors.affiliation: Institut für Medizinische Mikrobiologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany. Wichelhaus@em.uni-frankfurt.de
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Wichelhaus
authors.forename: Boris
authors.initials: B
authors.lastname: Böddinghaus
authors.forename: Silke
authors.initials: S
authors.lastname: Besier
authors.forename: Volker
authors.initials: V
authors.lastname: Schäfer
authors.forename: Volker
authors.initials: V
authors.lastname: Brade
authors.forename: Albrecht
authors.initials: A
authors.lastname: Ludwig
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D001483:Base Sequence; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000502:physiology*; D016521:Electrophoresis, Gel, Pulsed-Field; D005838:Genotype; D008969:Molecular Sequence Data; D012293:Rifampin / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000904:Antibiotics, Antitubercular; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin