TY - JOUR
T1 - Improved antimicrobial efficacy with nitric oxide releasing nanoparticle generated S-nitrosoglutathione
AU - Friedman, Adam J.
AU - Blecher, Karin
AU - Schairer, David
AU - Tuckman-Vernon, Chaim
AU - Nacharaju, Parimala
AU - Sanchez, David
AU - Gialanella, Philip
AU - Martinez, Luis R.
AU - Friedman, Joel M.
AU - Nosanchuk, Joshua D.
N1 - Funding Information:
A.J.F. gratefully acknowledges support from the Dermatology Foundation, Women’s Dermatologic Society, Centocor Ortho Biotech and La Roche Posay North American Foundation. L.R.M. gratefully acknowledges support from Long Island University.
PY - 2011/11/30
Y1 - 2011/11/30
N2 - Nitric oxide (NO) plays a vital role in mammalian host defense through a variety of mechanisms. In particular, NO can oxidize to form reactive nitrogen species or interact with protein thiols and metal centers, blocking essential microbial processes. S-nitrosoglutathione (GSNO), a potent NO donor formed by the interaction of NO with intracellular glutathione (GSH), is a major factor in this pathway and is considered one of the strongest naturally occurring nitrosating agent. We previously described the broad-spectrum antimicrobial activity of a nanoparticulate platform capable of controlled and sustained release of NO (NO-np). Interestingly, in vivo efficacy of the NO-np surpassed in vitro data generated. We hypothesized that the enhanced activity was in part achieved via the interaction between the generated NO and available GSH, forming GSNO. In the current study, we investigated the efficiency of NO-np to form GSNO in the presence of GSH was evaluated, and assessed the antimicrobial activity of the formed GSNO against methicillin resistant Staphylococcus aureus (MRSA), Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. When GSH was combined with NO-np, GSNO was rapidly produced and significant concentrations of GSNO were maintained for >24 h. The GSNO generated was more effective compared to NO-np alone against all bacterial strains examined, with P. aeruginosa being the most sensitive and K. pneumoniae the most resistant. We conclude that the combination of NO-np with GSH is an effective means of generating GSNO, and presents a novel approach to potent antimicrobial therapy.
AB - Nitric oxide (NO) plays a vital role in mammalian host defense through a variety of mechanisms. In particular, NO can oxidize to form reactive nitrogen species or interact with protein thiols and metal centers, blocking essential microbial processes. S-nitrosoglutathione (GSNO), a potent NO donor formed by the interaction of NO with intracellular glutathione (GSH), is a major factor in this pathway and is considered one of the strongest naturally occurring nitrosating agent. We previously described the broad-spectrum antimicrobial activity of a nanoparticulate platform capable of controlled and sustained release of NO (NO-np). Interestingly, in vivo efficacy of the NO-np surpassed in vitro data generated. We hypothesized that the enhanced activity was in part achieved via the interaction between the generated NO and available GSH, forming GSNO. In the current study, we investigated the efficiency of NO-np to form GSNO in the presence of GSH was evaluated, and assessed the antimicrobial activity of the formed GSNO against methicillin resistant Staphylococcus aureus (MRSA), Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. When GSH was combined with NO-np, GSNO was rapidly produced and significant concentrations of GSNO were maintained for >24 h. The GSNO generated was more effective compared to NO-np alone against all bacterial strains examined, with P. aeruginosa being the most sensitive and K. pneumoniae the most resistant. We conclude that the combination of NO-np with GSH is an effective means of generating GSNO, and presents a novel approach to potent antimicrobial therapy.
KW - Antibacterial
KW - Gram negative
KW - Gram positive
KW - Nanotechnology
KW - Nitric oxide
KW - S-Nitrosoglutathione
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UR - http://www.scopus.com/inward/citedby.url?scp=80053910033&partnerID=8YFLogxK
U2 - 10.1016/j.niox.2011.09.001
DO - 10.1016/j.niox.2011.09.001
M3 - Article
C2 - 21946032
AN - SCOPUS:80053910033
SN - 1089-8603
VL - 25
SP - 381
EP - 386
JO - Nitric Oxide - Biology and Chemistry
JF - Nitric Oxide - Biology and Chemistry
IS - 4
ER -