Confocal images for Mycobacteria biofilm from: Lipoarabinomannan regulates septation in Mycobacterium smegmatis

The growth and division of mycobacteria, which include several clinically
relevant pathogens, deviate significantly from that of canonical bacterial
models. Despite their Gram-positive ancestry, mycobacteria synthesize and
elongate a diderm envelope asymmetrically from the poles, with the old
pole elongating more robustly than the new pole. In addition to being
structurally distinct, the molecular components of the mycobacterial
envelope are also evolutionarily unique, including the
phosphatidylinositol-anchored lipoglycans lipomannan (LM) and
lipoarabinomannan (LAM). LM and LAM modulate host immunity during
infection, but their role outside of intracellular survival remains poorly
understood, despite their widespread conservation among non-pathogenic and
opportunistically pathogenic mycobacteria.
Previously, Mycobacterium
smegmatis and Mycobacterium
tuberculosis mutants producing structurally altered LM and LAM
were shown to grow slowly under certain conditions and to be more
sensitive to antibiotics, suggesting that mycobacterial lipoglycans may
support cellular integrity or growth. To test this, we constructed
multiple biosynthetic lipoglycan mutants of M. smegmatis and
determined the effect of each mutation on cell wall biosynthesis, envelope
integrity, and division. We found that mutants deficient in LAM, but not
LM, fail to maintain cell wall integrity in a medium-dependent manner,
with envelope deformations specifically associated with septa and new
poles. Conversely, a mutant producing abnormally large LAM formed
multiseptated cells in way distinct from that observed in a septal
hydrolase mutant. These results show that LAM plays critical and distinct
roles at subcellular locations associated with division in mycobacteria,
including maintenance of local cell envelope integrity and septal
placement.