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 grou ...

compound found in ''

Bacillus ''Bacillus'', from Latin "bacillus", meaning "little staff, wand", 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-sh ...

'' 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 urinary tract infections. It is not indicated for kidney infections. Occasionally it is used for prostate infections. It is generally ...

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 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 posi ...

'' and ''

Deinococcus radiodurans ''Deinococcus radiodurans'' is a bacterium, an extremophile and one of the most radiation-resistant organisms known. It can survive cold, dehydration, vacuum, and acid, and therefore is known as a polyextremophile. ''The Guinness Book Of 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 ty ...

''. 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 Chemical compound, compounds with the structure , where the R's represent a radical (a portion of a complete molecule; not necessarily a free radical) and O's are single oxygen atoms. Oxygen atoms are joined ...

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

glutathione Glutathione (GSH, ) is an organic compound with the chemical formula . It 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 ...

, which is the most common intracellular

in eukaryotes and some bacteria. Some of the genes involved in the biosynthesis of bacillithiol were identified and characterised 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, an acetyl group is a functional group denoted by 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, an acetyl grou ...

. 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