Dual membrane-spanning anti-sigma 2 controls OMV biogenesis and colonization fitness in Bacteroides thetaiotaomicron

Dual membrane-spanning anti-sigma factors (Dma) are a novel class of regulatory proteins found solely among Bacteroidota. Previous studies demonstrated the importance of Dma1 in vesiculation, but the overall role of the Dma family in Bacteroides physiology remains poorly understood. Here, we show that Dma2 modulates vesiculation and the expression of select polysaccharide utilization loci (PULs) that target host-associated glycans in vitro. Mouse studies revealed that Dma2 is an important fitness determinant in vivo when competing against kin bacteria. This work begins characterizing the multifaceted involvement of Dma2 in OMV biogenesis, PUL regulation, and colonization fitness.