Bacillithiol (BSH or Cys-GlcN-mal) is a

thiol In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl gro ...

compound found in ''

Bacillus ''Bacillus'' (Latin "stick") is a genus of Gram-positive, rod-shaped bacteria, a member of the phylum ''Bacillota'', with 266 named species. The term is also used to describe the shape (rod) of other so-shaped bacteria; and the plural ''Bacilli ...

'' species. It is likely involved in maintaining cellular redox balance and plays a role in microbial resistance to the antibiotic

fosfomycin Fosfomycin, sold under the brand name Monurol among others, is an antibiotic primarily used to treat lower UTI. It is not indicated for kidney infections. Occasionally it is used for prostate infections. It is generally taken by mouth. Common ...

Structure

Chemically, it is a glycoside formed between L-cysteinyl-D-glucosamine and

malic acid Malic acid is an organic compound with the molecular formula . It is a dicarboxylic acid that is made by all living organisms, contributes to the sour taste of fruits, and is used as a food additive. Malic acid has two stereoisomeric forms ...

. It was isolated and identified (as its bacillithiol-S-

bimane Bimane is a heterocyclic chemical compound A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A mol ...

derivative) in 2009 from ''

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 positive ...

'' and ''

Deinococcus radiodurans ''Deinococcus radiodurans'' is an extremophilic bacterium and one of the most radiation-resistant organisms known. It can survive cold, dehydration, vacuum, and acid, and therefore is known as a polyextremophile. It has been listed as the world ...

'', although it was first detected in 2007, as an unidentified thiol in ''

Bacillus anthracis ''Bacillus anthracis'' is a gram-positive and rod-shaped bacterium that causes anthrax, a deadly disease to livestock and, occasionally, to humans. It is the only permanent ( obligate) pathogen within the genus ''Bacillus''. Its infection is a ...

''. The naturally occurring free thiol form of bacillithiol has since been synthesised and characterised along with its biosynthetic precursors and its symmetrical disulfide.

Biological role

Bacillithiol appears to participate in the sensing of

peroxide In chemistry, peroxides are a group of compounds with the structure , where R = any element. The group in a peroxide is called the peroxide group or peroxo group. The nomenclature is somewhat variable. The most common peroxide is hydrogen p ...

s by ''Bacillus'', but may also substitute for

glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pero ...

, which is the most common intracellular thiol in eukaryotes and some bacteria. Some of the genes involved in the biosynthesis of bacillithiol were identified and characterized in 2010. Bacteria engineered to be deficient in bacillithiol demonstrated increased sensitivity to various electrophilic

xenobiotic A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...

compounds, including the antibiotic

, suggesting that in these organisms the mechanism of fosfomycin resistance relies on the presence of bacillithiol. Furthermore, ''in vitro'' kinetic studies have established that bacillithiol is a preferred thiol substrate for the antibiotic resistance enzyme FosB.

Biosynthesis

Bacillithiol is produced via the enzymes BshA, BshB, and BshC. BshA replaces the UDP group on UDP-''N''-acetylglucosamine with an L-malyl group. BshB then removes the

acetyl group In organic chemistry, acetyl is a functional group with the chemical formula and the structure . It is sometimes represented by the symbol Ac (not to be confused with the element actinium). In IUPAC nomenclature, acetyl is called ethanoyl, ...

. L-Cysteine is added to the resulting free amine, which completes the biosynthesis of the molecule. The cysteine-adding step is assumed to be carried out by the enzyme BshC on the basis of genetic knockout studies, but the activity of BshC has not been observed ''in vitro''.

References

{{reflist Thiols Propionamides Dicarboxylic acids Hexosamines

Structure

Biological role

Biosynthesis

See also

References