β-1,6-Glucan plays a central role in the structure and remodeling of the bilaminate fungal cell wall

β-1,6-glucan is primarily linear and contains short side chains of β-1,3-glucoside or laminaribioside residues.

“β−1,6-glucan is primarily linear and contains short side chains of β−1,3-glucoside or laminaribioside residues36,62.”

Mannan components often account for 30-40% of the cell wall polysaccharides and are linked to the β-1,3-glucan-chitin network either via the β-1,6-glucan moiety or directly.

“These mannan components, which often account for 30–40% of the cell wall polysaccharides, are linked to the β−1,3-glucan-chitin network either via the β−1,6-glucan moiety or directly36.”

β-1,6-glucan plays a critical role in adaptive remodeling of the Candida cell wall.

“Deletion of KRE6a, which encodes β−1,6-glucan synthase, reduces echinocandin susceptibility in C. auris, further highlighting β−1,6-glucan’s critical role in adaptive remodeling.”

A reduction in β-1,6-glucan level has been reported in the literature for C. albicans during caspofungin treatment, along with an increase in the molecular size of β-1,6-glucan and cross-linking of glucan and chitin.

“In addition to the inhibition of the biosynthesis of the primary target, β-1,3-glucan, a reduction in β-1,6-glucan level has also been reported in the literature for C. albicans during caspofungin treatment80, along with an increase in the molecular size of β-1,6-glucan and cross-linking of glucan and chitin36.”

β-1,6-glucan appears to be a key differentiating factor in the responses of C. albicans and C. auris to caspofungin treatment.

“Thus, β-1,6-glucan, which plays a crucial role in morphogenesis, cell wall integrity, and virulence36,81,82, appears to be a key differentiating factor in the responses of C. albicans and C. auris to caspofungin treatment.”

β-1,6-glucans have been shown recently to be highly responsive to environmental factors such as pH, salt, and presence of antifungals, and can be regulated to compensate for defects in O-/N-mannan elongation.

“The biosynthesis and structure of β-1,6-glucans is also a crucial but under-investigated component of the Candida cell wall, which have been shown recently to be highly responsive to environmental factors such as pH, salt, and the presence of antifungals, and can be regulated to compensate for defects in O-/N-mannan elongation36.”

β-1,6-glucan appears to play critical roles in interacting with both mannan and chitin, as suggested by solid-state NMR results, and may exhibit different behaviors between C. albicans and C. auris in response to echinocandins.

“Another underexplored molecule is β-1,6-glucan36,82, which appears to play critical roles in interacting with both mannan and chitin, as suggested by solid-state NMR results, and may exhibit different behaviors between C. albicans and C. auris in response to echinocandins.”