Molecular basis of phosphatidyl-myo-inositol mannoside biosynthesis and regulation in mycobacteria
Marcelo E Guerin1, Jana Korduláková, Pedro M Alzari
1Unidad de Biofisica, Centro Mixto Consejo Superior de Investigaciones Cientificas-Universidad del País Vasco/Euskal Herriko Unibertsitatea, Leioa, Bizkaia 48940, Spain. mrcguerin@gmail.com
Abstract:
Phosphatidyl-myo-inositol mannosides (PIMs) are unique glycolipids found in abundant quantities in the inner and outer membranes of the cell envelope of all Mycobacterium species. They are based on a phosphatidyl-myo-inositol lipid anchor carrying one to six mannose residues and up to four acyl chains. PIMs are considered not only essential structural components of the cell envelope but also the structural basis of the lipoglycans (lipomannan and lipoarabinomannan), all important molecules implicated in host-pathogen interactions in the course of tuberculosis and leprosy. Although the chemical structure of PIMs is now well established, knowledge of the enzymes and sequential events leading to their biosynthesis and regulation is still incomplete. Recent advances in the identification of key proteins involved in PIM biogenesis and the determination of the three-dimensional structures of the essential phosphatidyl-myo-inositol mannosyltransferase PimA and the lipoprotein LpqW have led to important insights into the molecular basis of this pathway.
Insights
Phosphatidyl-myo-inositol mannosides (PIMs) are essential Mycobacterium cell envelope components. Recent research illuminates the enzymes and structures involved in PIM biosynthesis, crucial for understanding host-pathogen interactions in tuberculosis and leprosy.
Area of Science:
- Microbiology
- Glycobiology
- Structural Biology
Background:
- Phosphatidyl-myo-inositol mannosides (PIMs) are vital glycolipids in Mycobacterium cell envelopes.
- PIMs form the structural basis for lipoglycans, key in host-pathogen interactions for tuberculosis and leprosy.
- The biosynthesis pathway and regulation of PIMs remain incompletely understood.
Purpose of the Study:
- To elucidate the molecular mechanisms and enzymes governing PIM biosynthesis in Mycobacterium species.
- To gain insights into the structural basis of PIM pathway enzymes and regulatory proteins.
Main Methods:
- Identification of key proteins involved in PIM biogenesis.
- Determination of three-dimensional structures of phosphatidyl-myo-inositol mannosyltransferase (PimA) and lipoprotein LpqW.
Main Results:
- Advances in identifying critical proteins for PIM synthesis.
- Structural determination of essential enzymes like PimA and regulatory proteins like LpqW.
Conclusions:
- Recent structural and protein identification studies provide significant insights into the PIM biosynthesis pathway.
- Further understanding of PIM biogenesis is crucial for targeting Mycobacterium infections.
Related Concept Videos
Phosphoinositides and PIPs
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Biosynthesis of Lipids
IP3/DAG Signaling Pathway
Biosynthesis of Polysaccharides
Biosynthesis of Nucleic Acids
Biosynthesis in Bacteria


