Transcriptomics and systems biology identify non-antibiotic drugs for the treatment of ocular bacterial infection

Reimagining the Past: A Future for Antibiotic Drug Discovery in Ophthalmology

“…The continued search for new antibiotics in the face of increasing resistance of current medications remains a daunting task. De novo antibiotic drug discovery has stalled in the FDA-approved antibacterial agent Delafloxacin 23,24 Antibacterial; skin and soft tissue infections Taurolidine 25 Disinfectant; catheter-related infections Thymosin beta-4 26 Antimicrobial peptide; neurotrophic keratitis Nisin 27 Antimicrobial peptide; food preservative Polymyxin B/trimethoprim + rifampin 13,15,31,32 Antibacterial combination; rifampin-tuberculosis infections Polymyxin B/trimethoprim-conjunctivitis Dequalinium chloride 38 Antiseptic; oral infections FDA-approved non-antibacterial agent Clofilium tosylate 38 Cardiac antiarrhythmic Glybenclamide 38 Diabetic agent Cisplatin 40 Chemotherapeutic…”

“…To expand beyond repurposing current antimicrobial agents, in the current big data era, new screening methods can now be used not only for de novo drug discovery but also for repurposing existing drugs that may have otherwise not have been considered. For example, Das et al 38 used an in silico and retinal cell genetic profiling approach to identify potential anti- S. aureus agents among known non-antibiotic drugs. The gene-expression profiles of S. aureus -infected retinal cells were defined and screened against the connectivity map database, 39 a catalog of gene-expression data from cultured human cells in response to thousands of bioactive small molecules and FDA-approved drugs, to identify potential agents that could mitigate the often damaging host–immune response in the setting of ocular infections.…”