Regulation of surface architecture by symbiotic bacteria mediates host colonization.
Microbes occupy countless ecological niches in nature. Sometimes these environments may be on or within another organism, as is the case in both microbial infections and symbiosis of mammals. Unlike pathogens that establish opportunistic infections, hundreds of human commensal bacterial species establish a lifelong cohabitation with their hosts. Although many virulence factors of infectious bacteria have been described, the molecular mechanisms used during beneficial host-symbiont colonization remain almost entirely unknown. The novel identification of multiple surface polysaccharides in the important human symbiont Bacteroides fragilis raised the critical question of how these molecules contribute to commensalism. To understand the function of the bacterial capsule during symbiotic colonization of mammals, we generated B. fragilis strains deleted in the global regulator of polysaccharide expression and isolated mutants with defects in capsule expression. Surprisingly, attempts to completely eliminate capsule production are not tolerated by the microorganism, which displays growth deficits and subsequent reversion to express capsular polysaccharides. We identify an alternative pathway by which B. fragilis is able to reestablish capsule production and modulate expression of surface structures. Most importantly, mutants expressing single, defined surface polysaccharides are defective for intestinal colonization compared with bacteria expressing a complete polysaccharide repertoire. Restoring the expression of multiple capsular polysaccharides rescues the inability of mutants to compete for commensalism. These findings suggest a model whereby display of multiple capsular polysaccharides provides essential functions for bacterial colonization during host-symbiont mutualism.
Liu
Cui Hua
CH
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Lee
S Melanie
SM
Vanlare
Jordan M
JM
Kasper
Dennis L
DL
Mazmanian
Sarkis K
SK
D000818:Animals; D016667:Bacterial Capsules / Q000378:metabolism; D001441:Bacteroides fragilis / Q000235:genetics / Q000254:growth & development*; D015169:Colony Count, Microbial; D017353:Gene Deletion; D005798:Genes, Bacterial; D005856:Germ-Free Life; D006801:Humans; D051379:Mice; D010641:Phenotype; D011135:Polysaccharides, Bacterial / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D013499:Surface Properties; D013559:Symbiosis
D011135:Polysaccharides, Bacterial