Evaluation of the Antibiotic Properties of Glutathione
November 2013 | Volume 12 | Issue 11 | Original Article | 1272 | Copyright © November 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.
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
