A conserved shufflon as an intra genus regulatory strategy in gut microbiota

Abstract Gut microorganisms inhabit a highly dynamic environment characterized by fluctuating nutrients, phage predation, and host immune pressure. To cope with such unpredictability, bacteria often rely on phase variation – the rapid generation of phenotypic heterogeneity via reversible DNA inversions. While the presence of multiple inversions, so called shufflons, in polysaccharide utilization loci was reported in several bacterial gut species, their role in gene expression regulation is poorly understood. Here we report and characterize an intra genus conserved phase variation system in Bacteroidaceae, a dominant group of the mammalian gut microbiota. This system consists of a cassette of silent susCD transmembrane transporter genes and an invertase that drives the rapid positioning of individual inactive genes into a single active expression site. Consequently, individual bacteria within a colony express different transporters, while collectively maintaining expression of the full gene repertoire. The composition of the transporter cassette is dynamic and evolves through horizontal gene transfer across the genus while preserving a conserved architecture. This shufflon system generates persistent genetic and phenotypic diversity, enabling Bacteroidaceae populations to adapt rapidly to the fluctuating conditions in the mammalian gut.