Evaluation of in vitro and in vivo antibiotic efficacy against a novel bioluminescent Shigella flexneri

Sci Rep. 2019 Sep 19;9(1):13567. doi: 10.1038/s41598-019-49729-2.


Shigella spp., the bacteria responsible for shigellosis, are one of the leading causes of diarrheal morbidity and mortality amongst children. There is a pressing need for the development of novel therapeutics, as resistance of Shigella to many currently used antibiotics is rapidly emerging. This paper describes the development of robust in vitro and in vivo tools to study antibiotic efficacy against Shigella flexneri. A novel bioluminescent S. flexneri strain (S. flexneri lux1) was generated, which can be used in a mammalian epithelial cell co-culture assay to evaluate antibiotic intracellular and extracellular efficacy. In addition, the S. flexneri lux1 strain was used with an intraperitoneal (IP) murine model of shigellosis to test the efficacy of ciprofloxacin and ampicillin. Both antibiotics significantly reduced the observed radiance from the gastrointestinal tissue of infected mice compared to vehicle control. Furthermore, plated gastrointestinal tissue homogenate confirmed antibiotic treatment significantly reduced the S. flexneri infection. However, in contrast to the results generated with tissue homogenate, the radiance data was not able to distinguish between the efficacy of ampicillin and ciprofloxacin. Compared to traditional methods, these models can be utilized for efficient screening of novel antibiotics aiding in the discovery of new treatments against shigellosis.

MeSH terms

  • Ampicillin / administration & dosage
  • Ampicillin / pharmacology
  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacology
  • Cell Line
  • Ciprofloxacin / administration & dosage
  • Ciprofloxacin / pharmacology
  • Disease Models, Animal
  • Dysentery, Bacillary / drug therapy*
  • Dysentery, Bacillary / microbiology
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / microbiology
  • Humans
  • Injections, Intraperitoneal
  • Luciferases / genetics
  • Luciferases / metabolism*
  • Luminescent Agents / metabolism
  • Luminescent Measurements
  • Mice
  • Microbial Sensitivity Tests
  • Plasmids / genetics
  • Plasmids / metabolism
  • Shigella flexneri / drug effects*
  • Shigella flexneri / genetics
  • Shigella flexneri / metabolism


  • Anti-Bacterial Agents
  • Luminescent Agents
  • Ciprofloxacin
  • Ampicillin
  • Luciferases