Mpi recombinase globally modulates the surface architecture of a human commensal bacterium

doi:10.1073/pnas.1832655100

Mpi recombinase globally modulates the surface architecture of a human commensal bacterium

Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115

Edited by Jeffrey I. Gordon, Washington University School of Medicine, St. Louis, MO, and approved July 8, 2003 (received for review May 4, 2003)

Abstract

The mammalian gut represents a complex and diverse ecosystem, consisting of unique interactions between the host and microbial residents. Bacterial surfaces serve as an interface that promotes and responds to this dynamic exchange, a process essential to the biology of both symbionts. The human intestinal microorganism, Bacteroides fragilis, is able to extensively modulate its surface. Analysis of the B. fragilis genomic sequence, together with genetic conservation analyses, cross-species cloning experiments, and mutational studies, revealed that this organism utilizes an endogenous DNA inversion factor to globally modulate the expression of its surface structures. This DNA invertase is necessary for the inversion of at least 13 regions located throughout the genome, including the promoter regions for seven of the capsular polysaccharide biosynthesis loci, an accessory polysaccharide biosynthesis locus, and five other regions containing consensus promoter sequences. Bacterial DNA invertases of the serine site-specific recombinase family are typically encoded by imported elements such as phage and plasmids, and act locally on a single region of the imported element. In contrast, the conservation and unique global regulatory nature of the process in B. fragilis suggest an evolutionarily ancient mechanism for surface adaptation to the changing intestinal milieu during commensalism.

Footnotes

↵ * To whom correspondence should be addressed. E-mail: lcomstock{at}channing.harvard.edu.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: EtBr, ethidium bromide; IR, inverted repeat; MCR, Mpi-controlled region; Ssr, serine site-specific recombinase; Tsr, tyrosine site-specific recombinase.