Collected Thoughts on Mycobacterial Lipoarabinomannan, a Cell Envelope Lipoglycan

The presence of lipoarabinomannan (LAM) in the Mycobacterium tuberculosis (Mtb) cell envelope was first reported close to 100 years ago. Since then, numerous studies have been dedicated to the isolation, purification, structural definition, and elucidation of the biological properties of Mtb LAM. In this review, we present a brief historical perspective on the discovery of Mtb LAM and the herculean efforts devoted to structurally characterizing the molecule because of its unique structural and biological features. The significance of LAM remains high to this date, mainly due to its distinct immunological properties in conjunction with its role as a biomarker for diagnostic tests due to its identification in urine, and thus can serve as a point-of-care diagnostic test for tuberculosis (TB). In recent decades, LAM has been thoroughly studied and massive amounts of information on this intriguing molecule are now available. In this review, we give the readers a historical perspective and an update on the current knowledge of LAM with information on the inherent carbohydrate composition, which is unique due to the often puzzling sugar residues that are specifically found on LAM. We then guide the readers through the complex and myriad immunological outcomes, which are strictly dependent on LAM's chemical structure. Furthermore, we present issues that remain unresolved and represent the immediate future of LAM research. Addressing the chemistry, functions, and roles of LAM will lead to innovative ways to manipulate the processes that involve this controversial and fascinating biomolecule.