title: Evaluation of the antibiotic properties of glutathione.
abstract: Skin and soft tissue infections (SSTIs) are growing in prevalence in both the outpatient and inpatient settings and are some of the most common diseases seen by dermatologists, who are often the first point of care for these patients. Microbial resistance to antibiotics continues to rise as more virulent strains evolve, and strains predominantly found in the hospital setting are now being seen in the community. Therefore, innovative approaches to combat this trend are needed. Glutathione (GSH) is a well-described and established antioxidant. It participates in detoxification of xenobiotics, regulation of cellular growth, modulation of immune response, and maintenance of the thiol status of proteins and cellular cysteine levels. GSH is also known to have a regulatory effect on immune cells and even inherent antibacterial properties have been reported. To this end, the value of GSH as an antibiotic was evaluated by growing methicillin resistant S. aureus, E. coli, K. pneumoniae and P. aeruginosa strains isolated from human skin and soft tissue infection in the presence of GSH. At a physiologic concentration of 10 mM, GSH had no effect on bacterial growth. At concentrations above 50 mM, which created acidic conditions (pH < 4), bacterial growth was completely inhibited. When adjusted to physiologic pH, GSH exhibited a bacteriostatic effect in a concentration-dependent manner. Additionally, the cytotoxicity of GSH was evaluated in a murine cell line. GSH was relatively non-toxic to murine macrophages, even at the highest concentration tested (160 mM). These results suggest the potential utility of GSH for the prevention and/or as adjunctive treatment of infection, most significantly in disease states associated with GSH deficiency.
authors.forename: David O
authors.initials: DO
authors.lastname: Schairer
authors.forename: Jason S
authors.initials: JS
authors.lastname: Chouake
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Kutner
authors.forename: Joy
authors.initials: J
authors.lastname: Makdisi
authors.forename: Josh D
authors.initials: JD
authors.lastname: Nosanchuk
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Friedman
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D015995:Prevalence; D017192:Skin Diseases, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D018461:Soft Tissue Infections / Q000188:drug therapy* / Q000382:microbiology; D018675:Toxicity Tests
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D005978:Glutathione