Structure and Function of thed-Galactose Network in Enterobacteria

Abstract

ABSTRACTGalactose is important for the survival and virulence of bacteria. InEscherichia coli, galactose is utilized by the Leloir pathway, which is controlled by a complex network. To shed light on the potential functions the galactose network could perform, we performed bioinformatical analysis of reference genome sequences belonging to theEnterobacteriaceaefamily. We found that several genomes have reduced numbers of components compared to theE. coligalactose system, suggesting that the network can be optimized for different environments. Typically, genes are removed by deletions; however, inYersinia pestis, the galactose mutarotase (galM) gene is inactivated by a single-base-pair deletion. Lack of GalM activity indicates that the two anomers ofd-galactose are used for different purposes, α-d-galactose as a carbon source and β-d-galactose for induction of UDP-galactose synthesis for biosynthetic glycosylation. We demonstrate that activity of thegalMgene can be restored by different single-base-pair insertions. During the evolution ofY. pestisto become a vector-transmitted systemic pathogen, many genes were converted to pseudogenes. It is not clear whether pseudogenes are present to maintain meiotrophism or are in the process of elimination. Our results suggest that thegalMpseudogene has not been deleted because its reactivation may be beneficial in certain environments.IMPORTANCEEvolution of bacteria to populate a new environment necessarily involves reengineering of their molecular network. Members of theEnterobacteriaceaefamily of bacteria have diverse lifestyles and can function in a wide range of environments. In this study we performed bioinformatical analysis of 34 reference genome sequences belonging to theEnterobacteriaceaefamily to gain insight into the natural diversity of thed-galactose utilization network. Our bioinformatical analysis shows that in several species, some genes of the network are completely missing or are inactivated by large deletions. The only exception is the galactose mutarotase (galM) gene ofYersinia pestis, which is converted to a pseudogene by a single-base-pair deletion. In this paper, we discuss the possible consequences ofgalMinactivation on network function. We suggest thatgalMwas converted to a pseudogene rather than being deleted in evolution because its reactivation can be beneficial in certain environments.