Evaluation of the Antibiotic Properties of Glutathione

November 2013 | Volume 12 | Issue 11 | Original Article | 1272 | Copyright © 2013

David O. Schairer MD,a Jason S. Chouake MD,a Allison J. Kutner,a Joy Makdisi,a
Josh D. NosanchukMD,b,c and Adam J. Friedman MDd,e

aAlbert Einstein College of Medicine, Bronx, NY
bDivision of Infectious Disease, Department of Medicine; Albert Einstein College of Medicine, Bronx, NY
cDepartment of Microbiology and Immunology; Albert Einstein College of Medicine, Bronx, NY
dDivision of Dermatology, Department of Medicine; Albert Einstein College of Medicine, Bronx, NY
eDepartment of Physiology and Biophysics; Albert Einstein College of Medicine, Bronx, NY

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 10mM, 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.

J Drugs Dermatol. 2013;12(11):1272-1277.

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INTRODUCTION

There is no question that the discovery of antibiotics/antimicrobials was one of the greatest advances in healthcare. However, due to over utilization, they are also now associated with the emergence of resistance species.1 Antibiotic- resistant bacteria are growing in prevalence in both hospitals and the community.2 One well known example is Methicillin Resistant Staphylococcus aureus (MRSA), estimated to be responsible for up to 19,000 deaths per year in the United States.3 The increase in hospital admissions for SSTIs has been ascribed to the escalating number of MRSA infections.3-5 Furthermore, bacterial strains that were predominantly seen in the community or in health care settings are interchanging, and now being seen in both circumstances.6 Without a doubt, the most commonly affected site of these infections is the skin, and Staphylococcus species are the most frequent cause of skin and soft tissue infections (SSTIs) in the United States7. Bacterial SSTI’s are among the most common diseases seen by dermatologists, who are often the first point of care for these patients8. As the public health and economic burden of SSTIs rises, dermatologists continue to play a key role in identifying and managing these diseases, as well as accelerating new discoveries to help face this medical crisis head on.

Glutathione (GSH) protects against oxidative stress and is the most prevalent antioxidant in mammalian cells.9 Formed from cysteine, glycine and glutamate, GSH derives its antioxidant properties from cysteine’s thiol side chain. When exposed to a reactive oxygen species (ROS), the thiol side chains from two GSH molecules oxidize and form a disulfide bond, reducing the ROS. The product, glutathione disulfide (GSSG), can then be reduced back to GSH, maintaining GSH concentrations at a level sufficient to protect the cell from oxidative damage.

In addition to its antioxidant properties, several additional roles for GSH have been discovered.9,10 GSH can be conjugated to xenobiotics to promote their excretion into bile; it can act as a cysteine reservoir when it is broken down into its constituent amino acids. It provides a source of thiols that prevent excessive disulfide bond formation in proteins, thus preserving the protein conformation. It also regulates cellular growth

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