Apoptosis-mediated ADAM10 activation removes a mucin barrier promoting T cell efferocytosis.

Efferocytic clearance of apoptotic cells in general, and T cells in particular, is required for tissue and immune homeostasis. Transmembrane mucins are extended glycoproteins highly expressed in the cell glycocalyx that function as a barrier to phagocytosis. Whether and how mucins may be regulated during cell death to facilitate efferocytic corpse clearance is not well understood. Here we show that normal and transformed human T cells express a subset of mucins which are rapidly and selectively removed from the cell surface during apoptosis. This process is mediated by the ADAM10 sheddase, the activity of which is associated with XKR8-catalyzed flipping of phosphatidylserine to the outer leaflet of the plasma membrane. Mucin clearance enhances uptake of apoptotic T cells by macrophages, confirming mucins as an enzymatically-modulatable barrier to efferocytosis. Together these findings demonstrate a glycocalyx regulatory pathway with implications for therapeutic intervention in the clearance of normal and transformed apoptotic T cells.

The impact of genetic diversity on gene essentiality within the Escherichia coli species.

Bacteria from the same species can differ widely in their gene content. In Escherichia coli, the set of genes shared by all strains, known as the core genome, represents about half the number of genes present in any strain. Although recent advances in bacterial genomics have unravelled genes required for fitness in various experimental conditions, most studies have focused on single model strains. As a result, the impact of the species' genetic diversity on core processes of the bacterial cell remains largely under-investigated. Here, we have developed a CRISPR interference platform for high-throughput gene repression that is compatible with most E. coli isolates and closely related species. We have applied it to assess the importance of ~3,400 nearly ubiquitous genes in three growth conditions in 18 representative E. coli strains spanning most common phylogroups and lifestyles of the species. Our screens revealed extensive variations in gene essentiality between strains and conditions. Investigation of the genetic determinants for these variations highlighted the importance of epistatic interactions with mobile genetic elements. In particular, we have shown how prophage-encoded defence systems against phage infection can trigger the essentiality of persistent genes that are usually non-essential. This study provides broad insights into the evolvability of gene essentiality and argues for the importance of studying various isolates from the same species under diverse conditions.