A22, also known as ''S''-(3,4-dichlorobenzyl) isothiourea, is a chemical compound with

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

activity. It is colorless,

hygroscopic Hygroscopy is the phenomenon of attracting and holding water molecules via either absorption (chemistry), absorption or adsorption from the surrounding Natural environment, environment, which is usually at normal or room temperature. If water mol ...

, and light-sensitive.

Antibiotic activity

A22 acts as a reversible inhibitor of the bacterial

cell wall A cell wall is a structural layer that surrounds some Cell type, cell types, found immediately outside the cell membrane. It can be tough, flexible, and sometimes rigid. Primarily, it provides the cell with structural support, shape, protection, ...

protein

MreB MreB is a protein found in bacteria that has been identified as a homologue of actin, as indicated by similarities in tertiary structure and conservation of active site peptide sequence. The conservation of protein structure suggests the commo ...

, causing bacterial rod-shaped cells to form

coccoid Coccoid means shaped like or resembling a coccus, that is, spherical.The noun coccoid or coccoids may refer to: * a level of organization, characterized by unicellular, non-flagellated, non-amoeboid organisms, with a definite shape, in general bu ...

cells. The antibiotic activity of A22 has been studied primarily in ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common Bacterial capsule, encapsulated, Gram-negative bacteria, Gram-negative, Aerobic organism, aerobic–facultative anaerobe, facultatively anaerobic, Bacillus (shape), rod-shaped bacteria, bacterium that can c ...

.'' However, A22 does not seem to be useful as an antibiotic in

human Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...

s due to its

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are toxic metals, toxic chemicals, microbe neurotoxins, radiation particles and even specific neurotransmitters when the system is out of balance. Also some types of dr ...

and

genotoxic Genotoxicity is the property of chemical agents that damage the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with mutagenicity, all mutagens are genotoxic, but some genotoxic s ...

effects on human

peripheral blood mononuclear cell A peripheral blood mononuclear cell (PBMC) is any peripheral blood cell having a round Cell nucleus, nucleus. These cells consist of lymphocytes (T cells, B cells, NK cells) and monocytes, whereas erythrocytes and platelets have no nuclei, and gr ...

s (PBMCs).

A22 as a research tool

Despite its cytotoxic effects in human cells, A22 has been used as a research tool to investigate the bacterial

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...

. A22 binds directly to the

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...

homolog MreB in its nucleotide-binding pocket, blocking simultaneous ATP binding. As a consequence, A22 inhibits MreB polymerization and thus disrupts the cytoskeleton of bacteria, causing defects of morphology and

chromosome A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...

segregation.

References

{{Reflist Antibiotics Thioureas Chloroarenes