Role of phase-variable Mfa1 fimbriae of Phocaeicola vulgatus in its adhesion and proinflammatory activity toward gut epithelial cells

Abstract

Bacteroidaceae is a prominent family in the human gut microbiota. The bacteria within this family are characterized by phase variable regulation of diverse surface structures, such as capsular polysaccharides and outer membrane proteins. We identified a genetic loci of Phocaeicola vulgatus ATCC8482 predicted to be involved in synthesis of an extracellular polysaccharides and fimbriae (type V pili). Promoter inversion (ON/OFF switch) mediated by two tyrosine recombinases (Tsr) controlled the expression of these genetic loci. Deletion of either tsr gene had no effect on inversion of either promoter. However, deletion of both tsr genes abolished promoter inversion in both regions, indicating the activity of these Tsr proteins with the distantly located promoters. Immunostaining of the major shaft protein of Mfa1 fimbriae in the tsr mutants showed that the expression of the fimbriae was controlled by the promoter inversions. P. vulgatus tsr mutant strain expressing the fimbrial proteins promoted aggregative adhesion and induced a proinflammatory response in the THP-1 human monocytic cell line, while P. vulgatus suppressed IL-8 production in human colonic epithelial cells regardless of the promoter orientation. These results indicate that the phase variable expression of these loci might be associated with the site-specific symbiotic/dysbiotic phenotype of P. vulgatus.

Keywords

• Phocaeicola vulgatus
• Mfa1 fimbriae
• phase variation
• colonization
• gut inflammation