A22, also known as ''S''-(3,4-dichlorobenzyl) isothiourea, is a chemical compound with antibiotic activity. It is colorless,

hygroscopic Hygroscopy is the phenomenon of attracting and holding water molecules via either absorption or adsorption from the surrounding environment, which is usually at normal or room temperature. If water molecules become suspended among the substan ...

, and light-sensitive.

Antibiotic activity

A22 acts as a reversible inhibitor of the bacterial cell wall 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 common a ...

, causing bacterial rod-shaped cells to form coccoid cells. The antibiotic activity of A22 has been studied primarily in ''

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. aerug ...

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

human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, cultu ...

s due to its cytotoxic 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 nucleus. These cells consist of lymphocytes (T cells, B cells, NK cells) and monocytes, whereas erythrocytes and platelets have no nuclei, and granulocytes ( ...

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 com ...

. 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 ov ...

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 long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

segregation.

References

{{Reflist Antibiotics Thioureas Chloroarenes