Abrogation of neuraminidase reduces biofilm formation, capsule biosynthesis, and virulence of Porphyromonas gingivalis.
The oral bacterium Porphyromonas gingivalis is a key etiological agent of human periodontitis, a prevalent chronic disease that affects up to 80% of the adult population worldwide. P. gingivalis exhibits neuraminidase activity. However, the enzyme responsible for this activity, its biochemical features, and its role in the physiology and virulence of P. gingivalis remain elusive. In this report, we found that P. gingivalis encodes a neuraminidase, PG0352 (SiaPg). Transcriptional analysis showed that PG0352 is monocistronic and is regulated by a sigma70-like promoter. Biochemical analyses demonstrated that SiaPg is an exo-α-neuraminidase that cleaves glycosidic-linked sialic acids. Cryoelectron microscopy and tomography analyses revealed that the PG0352 deletion mutant (ΔPG352) failed to produce an intact capsule layer. Compared to the wild type, in vitro studies showed that ΔPG352 formed less biofilm and was less resistant to killing by the host complement. In vivo studies showed that while the wild type caused a spreading type of infection that affected multiple organs and all infected mice were killed, ΔPG352 only caused localized infection and all animals survived. Taken together, these results demonstrate that SiaPg is an important virulence factor that contributes to the biofilm formation, capsule biosynthesis, and pathogenicity of P. gingivalis, and it can potentially serve as a new target for developing therapeutic agents against P. gingivalis infection.
Department of Oral Biology, The State University of New York at Buffalo, New York, USA.
Chen
C
Li
Kurniyati
Bo
B
Hu
Jiang
J
Bian
Jianlan
J
Sun
Weiyan
W
Zhang
Jun
J
Liu
Yaping
Y
Pan
Chunhao
C
Li
D000595:Amino Acid Sequence; D000818:Animals; D016667:Bacterial Capsules / Q000096:biosynthesis* / Q000648:ultrastructure; D016866:Bacteroidaceae Infections / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D018441:Biofilms / Q000254:growth & development*; D020285:Cryoelectron Microscopy; D004195:Disease Models, Animal; D055032:Electron Microscope Tomography; D017353:Gene Deletion; D006651:Histocytochemistry; D006805:Human Experimentation; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000201:enzymology* / Q000502:physiology* / Q000648:ultrastructure; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D016019:Survival Analysis; D014158:Transcription, Genetic; D014774:Virulence
D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid