Cis-encoded sRNAs repress expression of polysaccharide utilization loci in Bacteroides fragilis 638R

The phylum Bacteroidetes is a major component of the human gut microbiota which has a broad impact on the development and physiology of its host, and a potential role in a wide range of disease syndromes. The predominance of Bacteroidetes and the genus Bacteroides in the distal gut is due in large part to the expansion of paralogous gene clusters, termed Polysaccharide Utilization Loci (PULs), dedicated to the uptake and catabolism of host derived and dietary polysaccharides. It is generally thought that the diversity of PULs is key to Bacteroides successful competition for nutrients in the gut environment. The nutritive value of the available polysaccharides varies greatly and thus their utilization is hierarchical and strictly controlled. A typical PUL includes regulatory genes that control expression in response to the presence of specific glycan substrates. However the existence of additional regulatory mechanisms has been predicted to explain phenomena such as the hierarchical control, catabolite repression, and the fine tuning of gene expression to match catabolic activity. Using Bacteroides fragilis as a model organism, this report describes a previously unknown layer of regulatory control in which cis-encoded antisense small RNAs (sRNA) act as repressors of the PULs’ catabolic genes. Nearly 30% of B. fragilis PULs are subject to this type of sRNA control and these PULs tend to be more closely linked to the utilization of host-derived glycans than dietary polysaccharides. The findings described here indicate the presence of a global control mechanism that underlies the known regulatory circuits which modulate PUL expression in response to substrate availability, and hence provide novel insight into regulation of the gut Bacteroidetes physiology. This was a simple, single sample study to establish a baseline transcriptome during balanced growth in complex media.