title: Repression of invasion genes and decreased invasion in a high-level fluoroquinolone-resistant Salmonella typhimurium mutant.
abstract: BACKGROUND
  Nalidixic acid resistance among Salmonella Typhimurium clinical isolates has steadily increased, whereas the level of ciprofloxacin resistance remains low. The main objective of this study was to characterize the fluoroquinolone resistance mechanisms acquired in a S. Typhimurium mutant selected with ciprofloxacin from a susceptible isolate and to investigate its invasion ability.
  
  
  RESULTS
  Three different amino acid substitutions were detected in the quinolone target proteins of the resistant mutant (MIC of ciprofloxacin, 64 microg/ml): D87G and G81C in GyrA, and a novel mutation, E470K, in ParE. A protein analysis revealed an increased expression of AcrAB/TolC and decreased expression of OmpC. Sequencing of the marRAB, soxRS, ramR and acrR operons did not show any mutation and neither did their expression levels in a microarray analysis. A decreased percentage of invasion ability was detected when compared with the susceptible clinical isolate in a gentamicin protection assay. The microarray results revealed a decreased expression of genes which play a role during the invasion process, such as hilA, invF and the flhDC operon. Of note was the impaired growth detected in the resistant strain. A strain with a reverted phenotype (mainly concerning the resistance phenotype) was obtained from the resistant mutant.
  
  
  CONCLUSIONS
  In conclusion, a possible link between fluoroquinolone resistance and decreased cell invasion ability may exist explaining the low prevalence of fluoroquinolone-resistant S. Typhimurium clinical isolates. The impaired growth may appear as a consequence of fluoroquinolone resistance acquisition and down-regulate the expression of the invasion genes.
authors: Department of Microbiology, Hospital Clínic, School of Medicine, University of Barcelona, Barcelona, Spain.
authors: Anna
authors: A
authors: Fàbrega
authors: Laurence
authors: L
authors: du Merle
authors: Chantal
authors: C
authors: Le Bouguénec
authors: M Teresa
authors: MT
authors: Jiménez de Anta
authors: Jordi
authors: J
authors: Vila
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D009268:Nalidixic Acid / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012486:Salmonella typhimurium / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D009268:Nalidixic Acid; D002939:Ciprofloxacin