GSE128899
The distinct immune-stimulatory capacities of Porphyromonas gingivalis strains 381 and 33277 are determined by the fimB allele and gingipain activity
The genomes of P. gingivalis strains 33277 and 381 are highly related phylogenetically.  However,  33277  displays a reduced capacity to stimulate HEK cell TLR2-dependent signaling and THP-1 cell-dependent IL-1ß production compared to 381, suggesting strain-specific differences in the expression of one or more bacterial immune-modulatory cell surface molecules.  Genomic sequencing identified a single nucleotide polymorphism in the 33277 fimB allele (A>T), encoding a truncated FimB protein, relative to the 381 fimB allele. Gene exchange experiments indicated that the 33277 fimB allele contributes to the reduced immune-stimulatory capacity of this strain. Transcriptomic analyses determined that multiple genes related to carboxy-terminal domain (CTD) family proteins, including the gingipains, were upregulated in strain 33277 relative to strain 381.  A gingipain substrate degradation assay confirmed that cell surface gingipain activity is higher in 33277; and an isogenic mutant strain deficient for the gingipains exhibited an increased capacity to activate TLR2 signaling and induce IL-1ß production. Furthermore, 33277 and 381 isogenic mutant strains devoid of CTD cell surface proteins displayed increased immune-stimulatory capacities compared to the wild-type parental strains, confirming an immune-suppressive role for the gingipains.  Collectively, our data indicate that the combination of an intact fimB allele and limited cell surface gingipain expression in strain 381 contributes to its relatively potent immune-stimulatory activity.  Conversely, a defective fimB allele and high levels of cell surface gingipains reduce the capacity of strain 33277 to elicit host cell innate immune responses. Overall design: Transcriptional profiling of triplicate cultures of Porphyromonas gingivalis strains ATCC 33277 and 381.