Bacillithiol

Last updated
Bacillithiol
Bacillithiol.svg
Names
IUPAC name
(2S)-2-[2-(L-Cysteinamido)-2-deoxy-α-D-glucopyranosyloxy]butanedioic acid
Systematic IUPAC name
(2S)-2-({(2R,3R,4R,5S,6R)-3-[(2R)-2-Amino-3-sulfanylpropanamido]-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl}oxy)butanedioic acid
Identifiers
3D model (JSmol)
AbbreviationsCys-GlcN-mal
ChEBI
ChemSpider
PubChem CID
  • InChI=1S/C13H22N2O10S/c14-4(3-26)11(21)15-8-10(20)9(19)6(2-16)25-13(8)24-5(12(22)23)1-7(17)18/h4-6,8-10,13,16,19-20,26H,1-3,14H2,(H,15,21)(H,17,18)(H,22,23)/t4-,5-,6+,8+,9+,10+,13-/m0/s1 Yes check.svgY
    Key: UHNHELGKNQMNGF-AOQKXWSCSA-N Yes check.svgY
  • InChI=1/C13H22N2O10S/c14-4(3-26)11(21)15-8-10(20)9(19)6(2-16)25-13(8)24-5(12(22)23)1-7(17)18/h4-6,8-10,13,16,19-20,26H,1-3,14H2,(H,15,21)(H,17,18)(H,22,23)/t4-,5-,6+,8+,9+,10+,13-/m0/s1
    Key: UHNHELGKNQMNGF-AOQKXWSCBS
  • C([C@@H]1[C@H]([C@@H]([C@H]([C@H](O1)O[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CS)N)O)O)O
Properties
C13H22N2O10S
Molar mass 398.39 g/mol
Density 1.629 g/mL
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Bacillithiol (BSH or Cys-GlcN-mal) is a thiol compound found in Bacillus species. [1] It is likely involved in maintaining cellular redox balance and plays a role in microbial resistance to the antibiotic fosfomycin.

Contents

Structure

Chemically, it is a glycoside formed between L-cysteinyl-D-glucosamine and malic acid. It was isolated and identified (as its bacillithiol-S-bimane derivative) in 2009 from Staphylococcus aureus and Deinococcus radiodurans , [1] although it was first detected in 2007, as an unidentified thiol in Bacillus anthracis . [2] The naturally occurring free thiol form of bacillithiol has since been synthesised and characterised along with its biosynthetic precursors and its symmetrical disulfide. [3]

Biological role

Bacillithiol appears to participate in the sensing of peroxides by Bacillus, [4] but may also substitute for glutathione, which is the most common intracellular thiol in eukaryotes and some bacteria. [1] Some of the genes involved in the biosynthesis of bacillithiol were identified and characterized in 2010. [5] Bacteria engineered to be deficient in bacillithiol demonstrated increased sensitivity to various electrophilic xenobiotic compounds, including the antibiotic fosfomycin, suggesting that in these organisms the mechanism of fosfomycin resistance relies on the presence of bacillithiol. [5] Furthermore, in vitro kinetic studies have established that bacillithiol is a preferred thiol substrate for the antibiotic resistance enzyme FosB. [3] [6]

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. 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. [5] [7]

See also

Related Research Articles

<i>Bacillus</i> Genus of bacteria

Bacillus 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 is the name of the class of bacteria to which this genus belongs. Bacillus species can be either obligate aerobes which are dependent on oxygen, or facultative anaerobes which can survive in the absence of oxygen. Cultured Bacillus species test positive for the enzyme catalase if oxygen has been used or is present.

<span class="mw-page-title-main">Penicillin</span> Group of antibiotics derived from Penicillium fungi

Penicillins are a group of β-lactam antibiotics originally obtained from Penicillium moulds, principally P. chrysogenum and P. rubens. Most penicillins in clinical use are synthesised by P. chrysogenum using deep tank fermentation and then purified. A number of natural penicillins have been discovered, but only two purified compounds are in clinical use: penicillin G and penicillin V. Penicillins were among the first medications to be effective against many bacterial infections caused by staphylococci and streptococci. They are still widely used today for different bacterial infections, though many types of bacteria have developed resistance following extensive use.

<span class="mw-page-title-main">Neomycin</span> Type of antibiotic

Neomycin is an aminoglycoside antibiotic that displays bactericidal activity against gram-negative aerobic bacilli and some anaerobic bacilli where resistance has not yet arisen. It is generally not effective against gram-positive bacilli and anaerobic gram-negative bacilli. Neomycin comes in oral and topical formulations, including creams, ointments, and eyedrops. Neomycin belongs to the aminoglycoside class of antibiotics that contain two or more amino sugars connected by glycosidic bonds.

<span class="mw-page-title-main">Bacilli</span> Class of bacteria in the phylum Firmicutes

Bacilli is a taxonomic class of bacteria that includes two orders, Bacillales and Lactobacillales, which contain several well-known pathogens such as Bacillus anthracis. Bacilli are almost exclusively gram-positive bacteria.

<i>Mycobacterium leprae</i> Bacterium that causes leprosy

Mycobacterium leprae, is one of the two species of bacteria that cause Hansen’s disease (leprosy), a chronic but curable infectious disease that damages the peripheral nerves and targets the skin, eyes, nose, and muscles.

Lantibiotics are a class of polycyclic peptide antibiotics that contain the characteristic thioether amino acids lanthionine or methyllanthionine, as well as the unsaturated amino acids dehydroalanine, and 2-aminoisobutyric acid. They belong to ribosomally synthesized and post-translationally modified peptides.

A spheroplast is a microbial cell from which the cell wall has been almost completely removed, as by the action of penicillin or lysozyme. According to some definitions, the term is used to describe Gram-negative bacteria. According to other definitions, the term also encompasses yeasts. The name spheroplast stems from the fact that after the microbe's cell wall is digested, membrane tension causes the cell to acquire a characteristic spherical shape. Spheroplasts are osmotically fragile, and will lyse if transferred to a hypotonic solution.

<span class="mw-page-title-main">Mupirocin</span> Chemical compound

Mupirocin, sold under the brand name Bactroban among others, is a topical antibiotic useful against superficial skin infections such as impetigo or folliculitis. It may also be used to get rid of methicillin-resistant S. aureus (MRSA) when present in the nose without symptoms. Due to concerns of developing resistance, use for greater than ten days is not recommended. It is used as a cream or ointment applied to the skin.

The rpoB gene encodes the β subunit of bacterial RNA polymerase and the homologous plastid-encoded RNA polymerase (PEP). It codes for 1342 amino acids in E. coli, making it the second-largest polypeptide in the bacterial cell. It is targeted by the rifamycin family of antibacterials, such as rifampin. Mutations in rpoB that confer resistance to rifamycins do so by altering the protein's drug-binding residues, thereby reducing affinity for these antibiotics.

<span class="mw-page-title-main">Tyrocidine</span> Chemical compound

Tyrocidine is a mixture of cyclic decapeptides produced by the bacteria Bacillus brevis found in soil. It can be composed of 4 different amino acid sequences, giving tyrocidine A–D. Tyrocidine is the major constituent of tyrothricin, which also contains gramicidin. Tyrocidine was the first commercially available antibiotic, but has been found to be toxic toward human blood and reproductive cells. The function of tyrocidine within its host B. brevis is thought to be regulation of sporulation.

<span class="mw-page-title-main">Oritavancin</span> Pharmaceutical drug

Oritavancin, sold under the brand name Orbactiv among others, is a semisynthetic glycopeptide antibiotic medication for the treatment of serious Gram-positive bacterial infections. Its chemical structure as a lipoglycopeptide is similar to vancomycin.

<span class="mw-page-title-main">Thienamycin</span> Chemical compound

Thienamycin is one of the most potent naturally produced antibiotics known thus far, discovered in Streptomyces cattleya in 1976. Thienamycin has excellent activity against both Gram-positive and Gram-negative bacteria and is resistant to bacterial β-lactamase enzymes. Thienamycin is a zwitterion at pH 7.

<span class="mw-page-title-main">Fosfomycin</span> Chemical compound

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.

<span class="mw-page-title-main">O-succinylbenzoate—CoA ligase</span>

o-Succinylbenzoate—CoA ligase, encoded from the menE gene in Escherichia coli, catalyzes the fifth reaction in the synthesis of menaquinone. This pathway is called 1, 4-dihydroxy-2-naphthoate biosynthesis I. Vitamin K is a quinone that serves as an electron transporter during anaerobic respiration. This process of anaerobic respiration allows the bacteria to generate the energy required to survive.

<span class="mw-page-title-main">Mycothiol</span> Chemical compound

Mycothiol is an unusual thiol compound found in the Actinomycetota. It is composed of a cysteine residue with an acetylated amino group linked to glucosamine, which is then linked to inositol. The oxidized, disulfide form of mycothiol (MSSM) is called mycothione, and is reduced to mycothiol by the flavoprotein mycothione reductase. Mycothiol biosynthesis and mycothiol-dependent enzymes such as mycothiol-dependent formaldehyde dehydrogenase and mycothione reductase have been proposed to be good drug targets for the development of treatments for tuberculosis.

<span class="mw-page-title-main">Enzybiotics</span> Experimental antibacterial therapy

Enzybiotics are an experimental antibacterial therapy first described by Nelson, Loomis, and Fischetti. The term is derived from a combination of the words “enzyme” and “antibiotics.” Enzymes have been extensively utilized for their antibacterial and antimicrobial properties. Proteolytic enzymes called endolysins have demonstrated particular effectiveness in combating a range of bacteria and are the basis for enzybiotic research. Endolysins are derived from bacteriophages and are highly efficient at lysing bacterial cells. Enzybiotics are being researched largely to address the issue of antibiotic resistance, which has allowed for the proliferation of drug-resistant pathogens posing great risk to animal and human health across the globe.

<span class="mw-page-title-main">Epimerox</span> Chemical compound

Epimerox is an experimental broad-spectrum antibiotic compound being developed by scientists at the Rockefeller University and Astex Pharmaceuticals. It is a small molecule inhibitor compound that blocks the activity of the enzyme UDP-N-acetylglucosamine 2-epimerase, an epimerase enzyme that is called 2-epimerase for short.

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<span class="mw-page-title-main">Anthracimycin</span> Polyketide

Anthracimycin is a polyketide antibiotic discovered in 2013. Anthracimycin is derived from marine actinobacteria. In preliminary laboratory research, it has shown activity against Bacillus anthracis, the bacteria that causes anthrax, and against methicillin-resistant Staphylococcus aureus (MRSA).

<span class="mw-page-title-main">Cyclic di-AMP</span> Chemical compound

Cyclic di-AMP is a second messenger used in signal transduction in bacteria and archaea. It is present in many Gram-positive bacteria, some Gram-negative species, and archaea of the phylum euryarchaeota.

References

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