While multiple a 1–2-mannosidases are necessary for glycoprotein N-glycan maturation in vertebrates, a single bacterial a1–2-mannosidase can be sufficient to cleave all a1–2-linked mannose residues in host glycoprotein Nglycans. We report here the characterization and crystal structure of a new a1–2-mannosidase (EfMan-I) from Enterococcus faecalis, a Gram-positive opportunistic human pathogen. EfMan-I catalyzes the cleavage of a1–2-mannose from not only oligomannoses but also high-mannose-type N-glycans on glycoproteins. Its 2.15 A resolution crystal structure reveals a two-domain enzyme fold similar to other CAZy GH92 mannosidases. An unexpected potassium ion was observed bridging two domains near the active site. These findings support EfMan-I as an effective catalyst for in vitro N-glycan modification of glycoproteins with high-mannose-type N-glycans.

In this study, we aimed to determine the mechanisms underlying the initial extramedullary translocation of myeloma cells from bone marrow into peripheral blood. We found that clonal circulating plasma cells (cPCs) are more frequently detected by flow cytometry in extramedullary plasmacytoma (EMP) patients and worsen their prognosis. It is technically much easier to collect single cPCs using FACS than it is to perform EMP biopsy. Therefore, combining EMP imaging with cPC detection may be a promising strategy for prognostic stratification. Here, using single-cell transcriptome analysis, we found that the chemokine CXCL12, a key molecule involved in CXCR4-dependent cell retention in the bone marrow, is abnormally upregulated in cPCs and might initially enable cPCs to evade bone marrow retention and translocate into the bloodstream.