Hypothiocyanite
Hypothiocyanite is the
Hypothiocyanite is formed by peroxidase[1] catalysis of hydrogen peroxide and thiocyanate:
- H2O2 + SCN− → OSCN− + H2O
As a bactericide
Hypothiocyanite occurs naturally in the antimicrobial immune system of the human respiratory tract
Mechanism of action
Lactoperoxidase-catalysed reactions yield short-lived intermediary oxidation products of SCN−, providing antibacterial activity.[6]
The major intermediary oxidation product is hypothiocyanite OSCN−, which is produced in an amount of about 1 mole per mole of hydrogen peroxide. At the pH optimum of 5.3, the OSCN− is in equilibrium with HOSCN. The uncharged HOSCN is considered to be the greater bactericidal of the two forms.[7] At pH 7, it was evaluated that HOSCN represents 2% compare to OSCN− 98%.[8]
The action of OSCN− against bacteria is reported to be caused by sulfhydryl (SH) oxidation.[9]
The oxidation of -SH groups in the bacterial cytoplasmic membrane results in loss of the ability to transport glucose and also in leaking of potassium ions, amino acids and peptide.
OSCN− has also been identified as an antimicrobial agent in milk, saliva,[10] tears, and mucus.
OSCN− is considered as a safe product as it is not mutagenic.[11]
Relation to cystic fibrosis
Initially, this particular lactoperoxidase-catalyzed compound was originally discovered while viewing the specific environment of cystic fibrosis patients' weakened respiratory immune system against bacterial infection.[12]
Symptoms of cystic fibrosis include an inability to secrete sufficient quantities of SCN− which results in a shortage of necessary hypothiocyanite, resulting in increasing mucous viscosity, inflammation and bacterial infection in the respiratory tract.
Naturally, the discovery correlated with studies exploring different methods seeking to further gain alternative antibiotics, understanding that most older antibiotics are decreasing in effectiveness against bacteria with antibiotic resistance.[medical citation needed]
OSCN−, which is not an antibiotic, has proved efficacy on superbugs including MRSA reference strains, BCC, Mucoid PA[medical citation needed]
Schema of LPO/SCN−/H2O2 in human lung:
Efficacy range
Non exhaustive list of microorganisms.
Bacteria (Gram-positive and -negative)
- Acinetobacter spp.
- Aeromonas hydrophila
- Bacillus brevis
- Bacillus cereus
- Bacillus megaterium
- Bacillus subtilis
- Burkholderia cepacia
- Campylobacter jejuni
- Capnocytophaga ochracea
- Corynebacterium xerosis
- Enterobacter cloacae
- Escherichia coli
- Haemophilus influenzae
- Helicobacter pylori
- Klebsiella oxytoca
- Klebsiella pneumoniae
- Legionella spp.
- Listeria monocytogenes
- Micrococcus luteus
- Mycobacterium smegmatis
- Mycobacterium abscessus
- Neisseria spp.
- Pseudomonas aeruginosa
- Pseudomonas pyocyanea
- Salmonella spp.
- Selenomonas sputigena
- Shigella sonnei
- Staphylococcus aerogenes
- Staphylococcus aureus
- Streptococcus agalactiae
- Streptococcus faecalis
- Streptococcus mutans
- Wolinella recta
- Xanthomonas campestris
- Yersinia enterocolitica
Viruses[15]
- Echovirus 11
- Herpes simplex virus, HSV
- Influenza virus
- Human immunodeficiency virus, HIV
- Respiratory syncytial virus, RSV
Yeasts and moulds
- Aspergillus niger
- Botryodiplodia theobromae
- Byssochlamys fulva
- Candida albicans
- Colletotrichum gloeosporioide
- Colletotrichum musae
- Fusarium monoliforme
- Fusarium oxysporum
- Rhodotula rubra
- Sclerotinia spp.
See also
References
- PMID 16288970.
- PMID 19727356.
- PMID 17082494.
- PMID 6724690.
- S2CID 19490884.
- PMID 7066307.
- PMID 6832819.
- PMID 7248282.
- PMID 352945.
- PMID 11936452.
- PMID 6340603.
- PMID 19703552.
- ^ "Public summary of positive opinion for orphan designation of hypothiocyanite / lactoferrin for the treatment of cystic fibrosis" (PDF). Pre-authorisation Evaluation of Medicines for Human Use. European Medicines Agency. 2009-09-07. Archived from the original (PDF) on 2010-05-30. Retrieved 2010-01-23.
- ^ "Meveol: orphan drug status granted by the FDA for the treatment of cystic fibrosis". United States Food and Drug Administration. 2009-11-05. Archived from the original on 2009-12-24. Retrieved 2010-01-23.
- PMID 7605114.
Further reading
- Conner GE, Salathe M, Forteza R (December 2002). "Lactoperoxidase and hydrogen peroxide metabolism in the airway". Am. J. Respir. Crit. Care Med. 166 (12 Pt 2): S57–61. PMID 12471090.
- Conner GE, Wijkstrom-Frei C, Randell SH, Fernandez VE, Salathe M (January 2007). "The Lactoperoxidase System Links Anion Transport To Host Defense in Cystic Fibrosis". FEBS Lett. 581 (2): 271–8. PMID 17204267.
- Eastvold JS (2005). "Hypothiocyanous Acid: An Overview" (PDF). Free Radical Biology and Medicine.
- Minarowski Ł, Sands D, Minarowska A, Karwowska A, Sulewska A, Gacko M, Chyczewska E (2008). "Thiocyanate concentration in saliva of cystic fibrosis patients". Folia Histochem. Cytobiol. 46 (2): 245–6. PMID 18519245.
- Rada B, Leto TL (2009). "Redox warfare between airway epithelial cells and Pseudomonas: Dual oxidase versus pyocyanin". Immunol. Res. 43 (1–3): 198–209. PMID 18979077.
- Conner GE, Salathe M, Forteza R (December 2002). "Lactoperoxidase and hydrogen peroxide metabolism in the airway". Am. J. Respir. Crit. Care Med. 166 (12 Pt 2): S57–61. PMID 12471090.
- Fischer H (October 2009). "Mechanisms and Function of DUOX in Epithelia of the Lung". Antioxid. Redox Signal. 11 (10): 2453–65. PMID 19358684.
- Kussendrager KD, van Hooijdonk AC (November 2000). "Lactoperoxidase: physico-chemical properties, occurrence, mechanism of action and applications". Br. J. Nutr. 84 (Suppl 1): S19–25. PMID 11242442.
- Pedemonte N, Caci E, Sondo E, Caputo A, Rhoden K, Pfeffer U, Di Candia M, Bandettini R, Ravazzolo R, Zegarra-Moran O, Galietta LJ (April 2007). "Thiocyanate transport in resting and IL-4-stimulated human bronchial epithelial cells: role of pendrin and anion channels". J. Immunol. 178 (8): 5144–53. PMID 17404297.
- Rada B, Leto TL (2009). "Redox warfare between airway epithelial cells and Pseudomonas: Dual oxidase versus pyocyanin". Immunol. Res. 43 (1–3): 198–209. PMID 18979077.
- Rada B, Leto TL (2008). "Oxidative innate immune defenses by Nox/Duox family NADPH Oxidases". Trends in Innate Immunity. Contributions to Microbiology. Vol. 15. pp. 164–87. )
- Reiter B, Härnulv G (1984). "Lactoperoxidase antibacterial system natural occurrence, biological functions and practical applications". J Food Prot. 47 (9): 724–732. PMID 30934451.
- Shin K, Wakabayashi H, Yamauchi K, Teraguchi S, Tamura Y, Kurokawa M, Shiraki K (August 2005). "Effects of orally administered bovine lactoferrin and lactoperoxidase on influenza virus infection in mice". J. Med. Microbiol. 54 (Pt 8): 717–23. PMID 16014423.
- Thomas EL, Bates KP, Jefferson MM (September 1980). "Hypothiocyanite ion: detection of the antimicrobial agent in human saliva". J. Dent. Res. 59 (9): 1466–72. S2CID 7717994.
- Wijkstrom-Frei C, El-Chemaly S, Ali-Rachedi R, Gerson C, Cobas MA, Forteza R, Salathe M, Conner GE (August 2003). "Lactoperoxidase and human airway host defense". Am. J. Respir. Cell Mol. Biol. 29 (2): 206–12. PMID 12626341.
- Xu Y, Szép S, Lu Z (December 2009). "The antioxidant role of thiocyanate in the pathogenesis of cystic fibrosis and other inflammation-related diseases". Proc. Natl. Acad. Sci. U.S.A. 106 (48): 20515–9. PMID 19918082.