title: Molecular and phenotypic traits of in-vitro-selected mutants of Bifidobacterium resistant to rifaximin.
abstract: Nucleotide mutations inside a core region of the rpoB gene, encoding the beta subunit of RNA polymerase, were found in rifaximin-resistant mutants of Bifidobacterium. Five different missense mutations of codons 513, 516, 522 and 529 were identified. Further aspects of rifaximin resistance were investigated, using Bifidobacterium infantis BI07 as a model strain. Partial resistance of RNA polymerase of a BI07 mutant at a rifaximin concentration >10 microg/mL was observed by cell-free transcription assay. Mass spectrometry detection of rifaximin in the cellular pellet of the BI07 resistant mutant, as well as changes in biosynthesis of saturated and cyclopropane fatty acids during growth, suggested a reduction in membrane permeability for the antibiotic moiety.
authors.affiliation: Department of Pharmaceutical Sciences, University of Bologna, via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Vitali
authors.forename: Silvia
authors.initials: S
authors.lastname: Turroni
authors.forename: Stefania
authors.initials: S
authors.lastname: Serina
authors.forename: Margherita
authors.initials: M
authors.lastname: Sosio
authors.forename: Lucia
authors.initials: L
authors.lastname: Vannini
authors.forename: Marco
authors.initials: M
authors.lastname: Candela
authors.forename: Maria Elisabetta
authors.initials: ME
authors.lastname: Guerzoni
authors.forename: Patrizia
authors.initials: P
authors.lastname: Brigidi
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001644:Bifidobacterium / Q000187:drug effects*; D002462:Cell Membrane / Q000737:chemistry; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000235:genetics; D002849:Chromatography, Gas; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D005798:Genes, Bacterial; D013058:Mass Spectrometry; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012294:Rifamycins / Q000494:pharmacology*; D000078262:Rifaximin; D014158:Transcription, Genetic
chemical_list: D000900:Anti-Bacterial Agents; D005227:Fatty Acids; D012294:Rifamycins; D012321:DNA-Directed RNA Polymerases; D000078262:Rifaximin