Role of OmpA2 surface regions of Porphyromonas gingivalis in host-pathogen interactions with oral epithelial cells.
Outer membrane protein A (OmpA) is a key outer membrane protein found in Gram-negative bacteria that contributes to several crucial processes in bacterial virulence. In Porphyromonas gingivalis, OmpA is predicted as a heterotrimer of OmpA1 and OmpA2 subunits encoded by adjacent genes. Here we describe the role of OmpA and its individual subunits in the interaction of P. gingivalis with oral cells. Using knockout mutagenesis, we show that OmpA2 plays a significant role in biofilm formation and interaction with human epithelial cells. We used protein structure prediction software to identify extracellular loops of OmpA2, and determined these are involved in interactions with epithelial cells as evidenced by inhibition of adherence and invasion of P. gingivalis by synthetic extracellular loop peptides and the ability of the peptides to mediate interaction of latex beads with human cells. In particular, we observe that OmpA2-loop 4 plays an important role in the interaction with host cells. These data demonstrate for the first time the important role of P. gingivalis OmpA2 extracellular loops in interaction with epithelial cells, which may help design novel peptide-based antimicrobial therapies for periodontal disease.
School of Clinical Dentistry, University of Sheffield, Sheffield, United Kingdom.
Kathryn L
KL
Naylor
Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
Magdalena
M
Widziolek
School of Clinical Dentistry, University of Sheffield, Sheffield, United Kingdom.
Stuart
S
Hunt
School of Clinical Dentistry, University of Sheffield, Sheffield, United Kingdom.
Mary
M
Conolly
School of Clinical Dentistry, University of Sheffield, Sheffield, United Kingdom.
Matthew
M
Hicks
Biomolecular Research Centre, Sheffield Hallam University, City Campus, Sheffield, United Kingdom.
Prachi
P
Stafford
Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.|Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, Kentucky.
Jan
J
Potempa
School of Clinical Dentistry, University of Sheffield, Sheffield, United Kingdom.
Craig
C
Murdoch
School of Clinical Dentistry, University of Sheffield, Sheffield, United Kingdom.
C W Ian
CW
Douglas
School of Clinical Dentistry, University of Sheffield, Sheffield, United Kingdom.
Graham P
GP
Stafford
D001422:Bacterial Adhesion / Q000235:genetics / Q000502:physiology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D018441:Biofilms / Q000254:growth & development; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology; D005881:Gingiva / Q000166:cytology / Q000382:microbiology / Q000473:pathology*; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D008863:Microspheres; D010510:Periodontal Diseases / Q000382:microbiology* / Q000473:pathology; D016966:Porphyromonas gingivalis / Q000235:genetics / Q000472:pathogenicity*; D017433:Protein Structure, Secondary
D001425:Bacterial Outer Membrane Proteins; C078167:OMPA outer membrane proteins
OmpA proteins; host-pathogen interaction; oral microbiology; periodontal disease; porphyromonas gingivalis