Same Bacteria - Different Phenotype. A Bacterial Restriction Modification System Triggers Phenotypic Plasticity

Gut microbiome studies often aim to link specific bacteria to certain diseases. But is this link valid? Are two similar bacteria from two different hosts really the same? In this work, we characterized a type I Restriction-modification system of Bacteriodes fragilis, a common gut bacterium. This Type I system recognizes a specific foreign DNA that it can either restrict or modify by methylation. The recognition of the DNA sequence is done by a phase variable specificity protein. The phase variable protein consists of eight different possible recognition patterns where only one recognition pattern can be expressed at a time in a single bacterium. By RNAseq we found that each active specificity protein is correlated with a widespread change on the gene expression in the bacterium. One of the largest changes we observed was in the outer polysaccharide composition, which is an integral part of the host immune recognition system. Even though this type I Restriction-Modification system was traditionally thought as an innate immune system of the bacteria to combat foreign DNA or bacteriophage invasion, we found that there are profound alterations in this phase variable system even when put in a sterile environment such as the gut of germ-free mice. Our future plans are to identify mechanisms to control and modulate this system to express a specificity protein of our choice by applying engineered bacteriophages as a selection tool.