WGS_of_ciprofloxacin_exposed_S__Typhimurium-sc-6390
WGS_of_ciprofloxacin_exposed_S__Typhimurium
Fluoroquinolone resistance (FQR) in multi-drug resistant invasive non-typhoidal Salmonella Typhimurium is becoming a global health threat. To identify how FQR develops and affects the bacteria, including overall gene expression in the presence or absence of antibiotic, we will perform whole genome sequencing on reference clinical invasive non-typhoidal Salmonella isolate D23580. In particular, we are interested in what mutations occur in D23580 when it is continuously exposed to high levels of ciprofloxacin over 24 hours. We will compare the sequence of D23580 bacteria exposed to lethal doses of fluoroquinolones to those of untreated bacteria to identify single nucleotide polymorphisms that arise due to ciprofloxacin exposure. This analysis will give us a more complete understanding at the genotypic level of how FQR impacts S. Typhimurium survival and fitness.  This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
Antimicrobial resistance (AMR) is a pressing global health crisis, which has been fuelled by the sustained use of certain classes of antimicrobials, including the fluoroquinolones. While the genetic mutations responsible for decreased fluoroquinolone (ciprofloxacin) susceptibility are known, the implications of ciprofloxacin exposure on bacterial growth, survival, and interactions with host cells are not well described. Aiming to understand the influence of inhibitory concentrations of ciprofloxacin in vitro, we subjected three clinical isolates of S. Typhimurium to differing concentrations of ciprofloxacin, dependent on their minimum inhibitory concentrations (MIC), and assessed the impact on bacterial growth, morphology, and transcription. We further investigated the differential morphology and transcription that occurred following ciprofloxacin exposure and measured the ability of ciprofloxacin-treated bacteria to invade and replicate in host cells. We found that ciprofloxacin-exposed S. Typhimurium are able to recover from inhibitory concentrations of ciprofloxacin, and that the drug induces specific morphological and transcriptional signatures associated with the SOS response, DNA repair, and cellular survival. In addition, ciprofloxacin-treated S. Typhimurium have increased capacity for intracellular replication in comparison to untreated organisms. These data suggest that S. Typhimurium undergoes an adaptive response under ciprofloxacin perturbation that promotes cellular survival, a consequence that may justify more measured use of ciprofloxacin for Salmonella infections.  The combination of multiple experimental approaches provides new insights into the collateral effects that ciprofloxacin and other antimicrobials have on invasive bacterial pathogens.