mycolylarabinogalactanpeptidoglycan

Mycolylarabinogalactanpeptidoglycan (mAGP) is the characteristic cell wall complex of many bacteria in the suborder Corynebacterineae, most notably Mycobacterium species. It consists of three covalently linked polymers: a peptidoglycan scaffold, an arabinogalactan polymer, and covalently attached mycolic acids. The arabinogalactan is linked to the peptidoglycan, and the mycolic acids form a dense outer waxy layer by being esterified to the arabinogalactan. This architecture creates a thick, highly hydrophobic cell envelope that contributes to acid-fastness and low permeability.

Biosynthesis and assembly: Peptidoglycan precursors are synthesized in the cytoplasm, transported across the cytoplasmic membrane, and incorporated into the growing sacculus. The arabinogalactan component is produced by arabinosyltransferases (EmbCAB) that extend an arabinan domain onto a galactan backbone. The resulting arabinogalactan is covalently linked to the peptidoglycan via a linker region. Mycolic acids are then attached to arabinogalactan by mycolyltransferases of the antigen 85 complex (Ag85A, Ag85B, Ag85C), using donor mycolates such as trehalose dimycolate or trehalose monomycolate. In mycobacteria, the peptidoglycan can include unusual features such as N-glycolylmuramic acid and diverse cross-links, reflecting specialized enzymes like L,D-transpeptidases.

Function and clinical relevance: The mAGP envelope underpins the distinctive impermeability and resilience of these bacteria, influences host–pathogen interactions, and is a major determinant of acid-fast staining. It is a key antibiotic target: ethambutol inhibits Emb enzymes that construct the arabinogalactan, while isoniazid and related drugs disrupt mycolic acid synthesis. The mAGP structure is a hallmark of the Mycobacterium tuberculosis complex and related genera, and variations in its composition can affect virulence and resistance.