Inhibitory concentrations of ciprofloxacin induce an adaptive response promoting the intracellular survival of Salmonella enterica serovar Typhimurium
Antimicrobial resistance (AMR) is a pressing global health crisis, which has been fueled by the sustained use of certain classes of antimicrobials, including fluoroquinolones. While the genetic mutations responsible for decreased fluoroquinolone (ciprofloxacin) susceptibility are known, the implicat...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
American Society for Microbiology
2021
|
| _version_ | 1797056889602703360 |
|---|---|
| author | Sridhar, S Forrest, S Pickard, D Cormie, C Lees, EA Thomson, NR Dougan, G Baker, S |
| author_facet | Sridhar, S Forrest, S Pickard, D Cormie, C Lees, EA Thomson, NR Dougan, G Baker, S |
| author_sort | Sridhar, S |
| collection | OXFORD |
| description | Antimicrobial resistance (AMR) is a pressing global health crisis, which has been fueled by the sustained use of certain classes of antimicrobials, including 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 Salmonella enterica serovar Typhimurium to differing concentrations of ciprofloxacin, dependent on their MICs, 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 is able to recover from inhibitory concentrations of ciprofloxacin and that the drug induces specific morphological and transcriptional signatures associated with the bacterial SOS response, DNA repair, and intracellular survival. In addition, ciprofloxacin-treated S. Typhimurium has increased capacity for intracellular replication in comparison to that of 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. |
| first_indexed | 2024-03-06T19:28:50Z |
| format | Journal article |
| id | oxford-uuid:1cbf256c-96db-47a8-951e-9a3b490a7a22 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:28:50Z |
| publishDate | 2021 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | oxford-uuid:1cbf256c-96db-47a8-951e-9a3b490a7a222022-03-26T11:07:11ZInhibitory concentrations of ciprofloxacin induce an adaptive response promoting the intracellular survival of Salmonella enterica serovar TyphimuriumJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1cbf256c-96db-47a8-951e-9a3b490a7a22EnglishSymplectic ElementsAmerican Society for Microbiology2021Sridhar, SForrest, SPickard, DCormie, CLees, EAThomson, NRDougan, GBaker, SAntimicrobial resistance (AMR) is a pressing global health crisis, which has been fueled by the sustained use of certain classes of antimicrobials, including 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 Salmonella enterica serovar Typhimurium to differing concentrations of ciprofloxacin, dependent on their MICs, 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 is able to recover from inhibitory concentrations of ciprofloxacin and that the drug induces specific morphological and transcriptional signatures associated with the bacterial SOS response, DNA repair, and intracellular survival. In addition, ciprofloxacin-treated S. Typhimurium has increased capacity for intracellular replication in comparison to that of 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. |
| spellingShingle | Sridhar, S Forrest, S Pickard, D Cormie, C Lees, EA Thomson, NR Dougan, G Baker, S Inhibitory concentrations of ciprofloxacin induce an adaptive response promoting the intracellular survival of Salmonella enterica serovar Typhimurium |
| title | Inhibitory concentrations of ciprofloxacin induce an adaptive response promoting the intracellular survival of Salmonella enterica serovar Typhimurium |
| title_full | Inhibitory concentrations of ciprofloxacin induce an adaptive response promoting the intracellular survival of Salmonella enterica serovar Typhimurium |
| title_fullStr | Inhibitory concentrations of ciprofloxacin induce an adaptive response promoting the intracellular survival of Salmonella enterica serovar Typhimurium |
| title_full_unstemmed | Inhibitory concentrations of ciprofloxacin induce an adaptive response promoting the intracellular survival of Salmonella enterica serovar Typhimurium |
| title_short | Inhibitory concentrations of ciprofloxacin induce an adaptive response promoting the intracellular survival of Salmonella enterica serovar Typhimurium |
| title_sort | inhibitory concentrations of ciprofloxacin induce an adaptive response promoting the intracellular survival of salmonella enterica serovar typhimurium |
| work_keys_str_mv | AT sridhars inhibitoryconcentrationsofciprofloxacininduceanadaptiveresponsepromotingtheintracellularsurvivalofsalmonellaentericaserovartyphimurium AT forrests inhibitoryconcentrationsofciprofloxacininduceanadaptiveresponsepromotingtheintracellularsurvivalofsalmonellaentericaserovartyphimurium AT pickardd inhibitoryconcentrationsofciprofloxacininduceanadaptiveresponsepromotingtheintracellularsurvivalofsalmonellaentericaserovartyphimurium AT cormiec inhibitoryconcentrationsofciprofloxacininduceanadaptiveresponsepromotingtheintracellularsurvivalofsalmonellaentericaserovartyphimurium AT leesea inhibitoryconcentrationsofciprofloxacininduceanadaptiveresponsepromotingtheintracellularsurvivalofsalmonellaentericaserovartyphimurium AT thomsonnr inhibitoryconcentrationsofciprofloxacininduceanadaptiveresponsepromotingtheintracellularsurvivalofsalmonellaentericaserovartyphimurium AT dougang inhibitoryconcentrationsofciprofloxacininduceanadaptiveresponsepromotingtheintracellularsurvivalofsalmonellaentericaserovartyphimurium AT bakers inhibitoryconcentrationsofciprofloxacininduceanadaptiveresponsepromotingtheintracellularsurvivalofsalmonellaentericaserovartyphimurium |