Genomic analysis of Bacteroides fragilis reveals extensive DNA inversions regulating cell surface adaptation

Abstract

Bacteroides are predominant human colonic commensals, but the principal pathogenic species, Bacteroides fragilis (BF), lives closely associated with the mucosal surface, whereas a second major species, Bacteroides thetaiotaomicron (BT), concentrates within the colon. We find corresponding differences in their genomes, based on determination of the genome sequence of BF and comparative analysis with BT. Both species have acquired two mechanisms that contribute to their dominance among the colonic microbiota: an exceptional capability to use a wide range of dietary polysaccharides by gene amplification and the capacity to create variable surface antigenicities by multiple DNA inversion systems. However, the gene amplification for polysaccharide assimilation is more developed in BT, in keeping with its internal localization. In contrast, external antigenic structures can be changed more systematically in BF. Thereby, at the mucosal surface, where microbes encounter continuous attack by host defenses, BF evasion of the immune system is favored, and its colonization and infectious potential are increased.

Bacteroides: the Good, the Bad, and the Nitty-Gritty

“…While both B. thetaiotaomicron and B. fragilis contain large numbers of paralogous genes, comparison of the two genomes suggests that they are specifically tailored for their respective microenvironments. For example, B. fragilis has a pronounced capacity to create variable surface antigenicities by multiple DNA inversion systems (138). This surface-altering capability is more developed in B. fragilis, which is more frequently found at the mucosal surface (i.e., often the site of attack by host defenses) than is B. thetaiotaomicron.…”

“…The completion of the sequencing projects for B. thetaiotaomicron in 2003 (306) and B. fragilis in 2004 to 2005 (54,138) and subsequent proteomic analyses have vastly added to our understanding of the manner in which these organisms adapt to, and thrive in, the human gut. A few examples are (i) complex systems to sense the nutrient available and tailor nutrient-metabolizing systems accordingly, (ii) multiple pump systems to rid the bacteria of toxic substances, and (iii) the ability to control the environment by interacting with the host immune system so that it controls other (competing) pathogens.…”

A Bacteroides Conjugative Transposon, CTnERL, Can Transfer a Portion of Itself by Conjugation without Excising from the Chromosome

“…Surprisingly, about 80 to 90% of the CTnERL-related elements examined so far transfer intact under laboratory conditions. There are, however, several examples of cryptic, fragmentary CTn-type elements with various amounts of sequence identity to the CTnERL/CTnDOT family in the chromosomes of sequenced Bacteroides strains (8,28). Whether any of these CTns are still active for excision and transfer remains to be seen.…”

Mutations in yhiT enable utilization of exogenous pyrimidine intermediates in Salmonella enterica serovar Typhimurium

“…In particular, YhiT possesses conserved domains characteristic of the transporters DcuA and DcuB and shows similarity to DcuB of Bacteroides spp. (54 %) (Kuwahara et al, 2004;Xu et al, 2003), Mannheimia succiniciproducens (53 %) (Hong et al, 2004) and a variety of Campylobacterales (~46 %) (Fouts et al, 2005;Suerbaum et al, 2003), and to DcuA of Photorhabdus luminescens (54 %) (Duchaud et al, 2003) and members of the Campylobacterales (~45 %) (Fouts et al, 2005;Suerbaum et al, 2003;Tomb et al, 1997). Significantly, yhiT harboured the only nucleotide changes observed between the cloned DNA and published sequences, providing strong evidence that the mutant YhiT polypeptides manifest the pyrimidine utilization phenotype.…”