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Infection and Immunity, November 1998, p. 5337-5343, Vol. 66, No. 11
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Invasion of Aortic and Heart Endothelial Cells by
Porphyromonas gingivalis
Rajashri G.
Deshpande,1
Mahfuz B.
Khan,1 and
Caroline
Attardo Genco2,*
Department of Microbiology and Immunology,
Morehouse School of Medicine, Atlanta, Georgia
30320-1495,1 and
Department of Medicine,
Section of Infectious Diseases, Boston University School of
Medicine, Boston, Massachusetts 021182
Received 5 May 1998/Returned for modification 2 July 1998/Accepted 2 September 1998
Invasion of host cells is believed to be an important strategy
utilized by a number of pathogens, which affords them protection from
the host immune system. The connective tissues of the periodontium are
extremely well vascularized, which allows invading microorganisms, such
as the periodontal pathogen Porphyromonas gingivalis, to readily enter the bloodstream. However, the ability of P. gingivalis to actively invade endothelial cells has not been
previously examined. In this study, we demonstrate that P. gingivalis can invade bovine and human endothelial cells as
assessed by an antibiotic protection assay and by transmission and
scanning electron microscopy. P. gingivalis A7436 was
demonstrated to adhere to and to invade fetal bovine heart endothelial
cells (FBHEC), bovine aortic endothelial cells (BAEC), and human
umbilical vein endothelial cells (HUVEC). Invasion efficiencies of 0.1, 0.2, and 0.3% were obtained with BAEC, HUVEC, and FBHEC, respectively.
Invasion of FBHEC and BAEC by P. gingivalis A7436 assessed
by electron microscopy revealed the formation of microvillus-like
extensions around adherent bacteria followed by the engulfment of the
pathogen within vacuoles. Invasion of BAEC by P. gingivalis
A7436 was inhibited by cytochalasin D, nocodazole, staurosporine,
protease inhibitors, and sodium azide, indicating that cytoskeletal
rearrangements, protein phosphorylation, energy metabolism, and
P. gingivalis proteases are essential for invasion. In
contrast, addition of rifampin, nalidixic acid, and chloramphenicol had
little effect on invasion, indicating that bacterial RNA, DNA, and de
novo protein synthesis are not required for P. gingivalis
invasion of endothelial cells. Likewise de novo protein synthesis by
endothelial cells was not required for invasion by P. gingivalis.
P. gingivalis 381 was demonstrated to adhere to and to invade
BAEC (0.11 and 0.1% efficiency, respectively). However, adherence and
invasion of the corresponding fimA mutant DPG3, which lacks
the major fimbriae, was not detected. These results indicate that
P. gingivalis can actively invade endothelial cells and
that fimbriae are required for this process. P. gingivalis invasion of endothelial cells may represent another strategy utilized by this pathogen to thwart the host immune response.
*
Corresponding author. Mailing address: Department of
Medicine, Section of Infectious Diseases, Boston University School of Medicine, 774 Albany St., Boston, MA 02118. Phone: (617) 414-5282. Fax:
(617) 414-5280. E-mail: caroline.genco{at}bmc.org.
Infection and Immunity, November 1998, p. 5337-5343, Vol. 66, No. 11
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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