Molecular and phenotypic traits of in-vitro-selected mutants of Bifidobacterium resistant to rifaximin.
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.
Vitali
Beatrice
B
Department of Pharmaceutical Sciences, University of Bologna, via Belmeloro 6, 40126 Bologna, Italy.
Turroni
Silvia
S
Serina
Stefania
S
Sosio
Margherita
M
Vannini
Lucia
L
Candela
Marco
M
Guerzoni
Maria Elisabetta
ME
Brigidi
Patrizia
P
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
D000900:Anti-Bacterial Agents; D005227:Fatty Acids; D012294:Rifamycins; D012321:DNA-Directed RNA Polymerases; D000078262:Rifaximin