Hypothiocyanite
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Hypothiocyanite is the
anion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conve ...
SCN SCN may stand for: Science and technology *Switched circuit network, i.e. the public switched telephone network * Server change number, a counter variable used in client-server architecture *System change number, a stamp that defines a committed ...
sup>− and the
conjugate base A conjugate acid, within the Brønsted–Lowry acid–base theory, is a chemical compound formed when an acid donates a proton () to a base—in other words, it is a base with a hydrogen ion added to it, as in the reverse reaction it loses a ...
of hypothiocyanous acid (HOSCN). It is an
organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...
part of the thiocyanates as it contains the
functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the r ...
SCN. It is formed when an oxygen is singly bonded to the
thiocyanate Thiocyanate (also known as rhodanide) is the anion . It is the conjugate base of thiocyanic acid. Common derivatives include the colourless salts potassium thiocyanate and sodium thiocyanate. Mercury(II) thiocyanate was formerly used in pyr ...
group. Hypothiocyanous acid is a fairly weak acid; its
acid dissociation constant In chemistry, an acid dissociation constant (also known as acidity constant, or acid-ionization constant; denoted ) is a quantitative measure of the strength of an acid in solution. It is the equilibrium constant for a chemical reaction :HA ...
(p''K''a) is 5.3. Hypothiocyanite is formed by peroxidase 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 in a redox reaction catalyzed by the enzyme
lactoperoxidase Lactoperoxidase is a peroxidase enzyme secreted from mammary, salivary and other mucosal glands including the lungs, bronchii and nose that functions as a natural and the first line of defense against bacteria and viruses. Lactoperoxidase is a ...
. It has been researched extensively for its capabilities as an alternative antibiotic as it is harmless to human body cells while being cytotoxic to bacteria. The exact processes for making hypothiocyanite have been patented as such an effective antimicrobial has many commercial applications.


Mechanism of action

Lactoperoxidase-catalysed reactions yield short-lived intermediary oxidation products of SCN, providing antibacterial activity. 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. At pH 7, it was evaluated that HOSCN represents 2% compare to OSCN 98%. The action of OSCN against bacteria is reported to be caused by sulfhydryl (SH) oxidation. 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, tears, and mucus. OSCN is considered as a safe product as it is not mutagenic.


Relation to cystic fibrosis

Initially, this particular lactoperoxidase-catalyzed compound was originally discovered while viewing the specific environment of
cystic fibrosis Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. Ot ...
patients' weakened respiratory immune system against bacterial infection. 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.
Lactoferrin Lactoferrin (LF), also known as lactotransferrin (LTF), is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, s ...
with hypothiocyanite has been granted
orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...
status by the
EMEA EMEA is a shorthand designation meaning Europe, the Middle East and Africa. The acronym is used by institutions and governments, as well as in marketing and business when referring to this region: it is a shorthand way of referencing the two ...
and the FDA. 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. OSCN, which is not an antibiotic, has proved efficacy on superbugs including MRSA reference strains, BCC, Mucoid PA Schema of LPO/SCN/H2O2 in human
lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of ...


Efficacy range

Non exhaustive list of microorganisms. Bacteria (Gram-positive and -negative) *''
Acinetobacter ''Acinetobacter'' is a genus of gram-negative bacteria belonging to the wider class of Gammaproteobacteria. ''Acinetobacter'' species are oxidase-negative, exhibit twitching motility, and occur in pairs under magnification. They are importan ...
'' spp. *''
Aeromonas hydrophila ''Aeromonas hydrophila'' is a heterotrophic, Gram-negative, rod-shaped bacterium mainly found in areas with a warm climate. This bacterium can be found in fresh or brackish water. It can survive in aerobic and anaerobic environments, and can d ...
'' *'' Bacillus brevis'' *''
Bacillus cereus ''Bacillus cereus'' is a Gram-positive rod-shaped bacterium commonly found in soil, food, and marine sponges. The specific name, ''cereus'', meaning "waxy" in Latin, refers to the appearance of colonies grown on blood agar. Some strains are har ...
'' *'' Bacillus megaterium'' *''
Bacillus subtilis ''Bacillus subtilis'', known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium, found in soil and the gastrointestinal tract of ruminants, humans and marine sponges. As a member of the genus ''Bacillus ...
'' *''
Burkholderia cepacia ''Burkholderia cepacia'' complex (BCC), or simply ''Burkholderia cepacia'', is a group of catalase-producing, lactose-nonfermenting, Gram-negative bacteria composed of at least 20 different species, including ''B. cepacia'', '' B. m ...
'' *'' Campylobacter jejuni'' *''
Capnocytophaga ochracea ''Capnocytophaga'' is a genus of Gram-negative bacteria. Normally found in the oropharyngeal tract of mammals, they are involved in the pathogenesis of some animal bite wounds and periodontal diseases. Taxonomy The term ''Capnocytophaga'' com ...
'' *'' Corynebacterium xerosis'' *''
Enterobacter cloacae ''Enterobacter cloacae'' is a clinically significant Gram-negative, facultatively-anaerobic, rod-shaped bacterium. Microbiology In microbiology labs, ''E. cloacae'' is frequently grown at 30 °C on nutrient agar or at 35 °C in tr ...
'' *''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
'' *''
Haemophilus influenzae ''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, non-motile, coccobacillary, facultatively anaerobic, capnophilic pathogenic bacterium of the family Pasteurellaceae. The bact ...
'' *''
Helicobacter pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape (from which the genus name, helicobacter, derives) is thoug ...
'' *''
Klebsiella oxytoca ''Klebsiella oxytoca'' is a Gram-negative, rod-shaped bacterium that is closely related to '' K. pneumoniae'', from which it is distinguished by being indole-positive; it also has slightly different growth characteristics in that it is able to gr ...
'' *''
Klebsiella pneumoniae ''Klebsiella pneumoniae'' is a Gram-negative, non-motile, encapsulated, lactose- fermenting, facultative anaerobic, rod-shaped bacterium. It appears as a mucoid lactose fermenter on MacConkey agar. Although found in the normal flora of the mo ...
'' *''
Legionella ''Legionella'' is a genus of pathogenic gram-negative bacteria that includes the species '' L. pneumophila'', causing legionellosis (all illnesses caused by ''Legionella'') including a pneumonia-type illness called Legionnaires' disease and a mil ...
'' spp. *''
Listeria monocytogenes ''Listeria monocytogenes'' is the species of pathogenic bacteria that causes the infection listeriosis. It is a facultative anaerobic bacterium, capable of surviving in the presence or absence of oxygen. It can grow and reproduce inside the host ...
'' *'' Micrococcus luteus'' *''
Mycobacterium smegmatis ''Mycobacterium smegmatis'' is an acid-fast bacterial species in the phylum ''Actinomycetota'' and the genus ''Mycobacterium''. It is 3.0 to 5.0 µm long with a bacillus shape and can be stained by Ziehl–Neelsen method and the auramine-rh ...
'' *''
Mycobacterium abscessus ''Mycobacteroides abscessus'' (formerly ''Mycobacterium abscessus'') is a species of rapidly growing, multidrug-resistant, nontuberculous mycobacteria that is a common soil and water contaminant. Although ''M. abscessus'' most commonly causes ch ...
'' *''
Neisseria ''Neisseria'' is a large genus of bacteria that colonize the mucosal surfaces of many animals. Of the 11 species that colonize humans, only two are pathogens, '' N. meningitidis'' and ''N. gonorrhoeae''. ''Neisseria'' species are Gram-negativ ...
'' spp. *''
Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic– facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. a ...
'' *'' Pseudomonas pyocyanea'' *''
Salmonella ''Salmonella'' is a genus of rod-shaped (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two species of ''Salmonella'' are '' Salmonella enterica'' and '' Salmonella bongori''. ''S. enterica'' is the type species and is ...
'' spp. *''
Selenomonas sputigena Members of the genus ''Selenomonas'' (motile crescent-shaped bacteria in general) are referred to trivially as selenomonads. The genus ''Selenomonas'' constitutes a group of motile crescent-shaped bacteria and includes species living in the gas ...
'' *'' Shigella sonnei'' *'' Staphylococcus aerogenes'' *''
Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posit ...
'' *'' Streptococcus agalactiae'' *''
Streptococcus faecalis ''Enterococcus faecalis'' – formerly classified as part of the group D '' Streptococcus'' system – is a Gram-positive, commensal bacterium inhabiting the gastrointestinal tracts of humans. Like other species in the genus '' Enterococcus'' ...
'' *''
Streptococcus mutans ''Streptococcus mutans'' is a facultatively anaerobic, gram-positive coccus (round bacterium) commonly found in the human oral cavity and is a significant contributor to tooth decay. It is part of the "streptococci" (plural, non-italic lowerc ...
'' *'' Wolinella recta'' *''
Xanthomonas campestris ''Xanthomonas campestris'' is a bacterium that causes a variety of plant diseases, including "black rot" in cruciferous vegetables and bacterial wilt of turfgrass. It is also used in the commercial production of xanthan gum, a high-molecular-we ...
'' *''
Yersinia enterocolitica ''Yersinia enterocolitica'' is a Gram-negative, bacillus-shaped bacterium, belonging to the family Yersiniaceae. It is motile at temperatures of 22–29° C (72–84 °F), but becomes nonmotile at normal human body temperature. ''Y. enterocolit ...
'' Viruses *
Echovirus Echovirus is a polyphyletic group of viruses associated with enteric disease in humans. The name is derived from "enteric cytopathic human orphan virus". These viruses were originally not associated with disease, but many have since been identif ...
11 *
Herpes simplex virus Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomical names '' Human alphaherpesvirus 1'' and ''Human alphaherpesvirus 2'', are two members of the human ''Herpesviridae'' family, a set of viruses that produce viral in ...
, HSV *
Influenza virus ''Orthomyxoviridae'' (from Greek ὀρθός, ''orthós'' 'straight' + μύξα, ''mýxa'' 'mucus') is a family of negative-sense RNA viruses. It includes seven genera: ''Alphainfluenzavirus'', ''Betainfluenzavirus'', '' Gammainfluenzavirus'', ' ...
*
Human immunodeficiency virus The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immun ...
, HIV *
Respiratory syncytial virus Respiratory syncytial virus (RSV), also called human respiratory syncytial virus (hRSV) and human orthopneumovirus, is a common, contagious virus that causes infections of the respiratory tract. It is a negative-sense, single-stranded RNA virus. ...
, RSV Yeasts and moulds *''
Aspergillus niger ''Aspergillus niger'' is a mold classified within the ''Nigri'' section of the ''Aspergillus'' genus. The ''Aspergillus'' genus consists of common molds found throughout the environment within soil and water, on vegetation, in fecal matter, on de ...
'' *''
Botryodiplodia theobromae ''Lasiodiplodia theobromae'' is a plant pathogen with a very wide host range. It causes rotting and dieback in most species it infects. It is a common post harvest fungus disease of citrus known as stem-end rot. It is a cause of bot canker of g ...
'' *'' Byssochlamys fulva'' *''
Candida albicans ''Candida albicans'' is an opportunistic pathogenic yeast that is a common member of the human gut flora. It can also survive outside the human body. It is detected in the gastrointestinal tract and mouth in 40–60% of healthy adults. It is usu ...
'' *'' Colletotrichum gloeosporioide'' *'' Colletotrichum musae'' *''
Fusarium monoliforme ''Fusarium'' is a large genus of filamentous fungi, part of a group often referred to as hyphomycetes, widely distributed in soil and associated with plants. Most species are harmless saprobes, and are relatively abundant members of the soil m ...
'' *''
Fusarium oxysporum ''Fusarium oxysporum'' (Schlecht as emended by Snyder and Hansen), an ascomycete fungus, comprises all the species, varieties and forms recognized by Wollenweber and Reinking within an infrageneric grouping called section Elegans. It is part of ...
'' *'' Rhodotula rubra'' *'' Sclerotinia'' spp.


See also

*
Respiratory tract antimicrobial defense system The respiratory tract antimicrobial defense system is a layered defense mechanism which relies on components of both the innate and adaptive immune systems to protect the lungs and the rest of the respiratory tract against inhaled microorganisms. ...


References


Further reading

* * * * * * * * * * * * * * * * {{Refend Anions Thiocyanates Chemical pathology Sulfur ions