Bacterial cell wall arabinosyltransferase (AraT)

Bacterial cell wall arabinosyltransferases are a family of membrane-bound glycosyltransferase enzymes responsible for the synthesis of the arabinan domain of vital mycobacterial cell wall components, specifically arabinogalactan and lipoarabinomannan. These enzymes, including EmbA, EmbB, EmbC, AftA, AftB, and AftD, catalyze the transfer of arabinofuranose from the lipid donor decaprenyl-phosphate-arabinose (DPA) to growing polysaccharide chains, establishing various linkages essential for the structural integrity and function of the mycobacterial cell envelope[2][6][1][4][5]. These enzymes are essential for the viability and pathogenicity of mycobacteria and are validated therapeutic targets for tuberculosis, as exemplified by their inhibition by the first-line drug ethambutol, which blocks cell wall biosynthesis and leads to bacterial death[2][7][6]. Resistance frequently develops through mutations near the drug binding site, particularly in embB, challenging therapy and serving as clinical biomarkers[6].

Other names

ArabinosyltransferaseArabinofuranosyltransferaseEmbAEmbBEmbCAftAAftBAftD

Inhibition of arabinosyltransferase enzymes blocks the transfer of arabinose units, disrupting the synthesis of arabinan in arabinogalactan and lipoarabinomannan, leading to defective cell wall assembly and impaired bacterial survival[2][7][6]. Ethambutol inhibits by binding at the enzyme active site, directly competing with substrate binding[2][7].