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Host modulation of tissue destruction caused by periodontopathogens: effects on a mixed microbial infection composed of Porphyromonas gingivalis and Fusobacterium nucleatum.

These studies determined the ability of selected periodontopathogens to synergistically initiate soft tissue destruction in a murine abscess model. The development of immunity following recovery from infection or by active immunization was also examined. Mice were infected with P. gingivalis W50, F. nucleatum T18, or a combination of the two microorganisms. F. nucleatum caused only a localized lesion in contrast to P. gingivalis which caused a spreading suppurative inflammatory lesion of the skin and subcutaneous tissues, which, depending upon the dose, could result in death. Infection of mice with a combination of P. gingivalis and F. nucleatum elicited a significantly greater lesion size (P<0.001) and lethality compared with P. gingivalis alone. Mice infected with a subclinical dose (no visible lesion) of P. gingivalis failed to develop protective immunity to a secondary P. gingivalis challenge. Mice that had recovered from P. gingivalis lesions demonstrated partial protection against subsequent P. gingivalis challenge; however, the immunity was less protective against the mixed F. nucleatum + P. gingivalis infection. Active immunization with P. gingivalis protected against both the P. gingivalis and F. nucleatum + P. gingivalis challenges and this protection was correlated with the levels of specific serum immunoglobulin G (IgG) antibody. The results indicated that the murine model is ideally suited to examine bacterially-mediated mixed infections that result in soft tissue destruction. This destruction can be minimized, but not abrogated, with development of immunity. Challenge with sufficient numbers of the pathogens can overwhelm the acquired immunity.

Animals↗

Protein secretion systems in Fusobacterium nucleatum: genomic identification of Type 4 piliation and complete Type V pathways brings new insight into mechanisms of pathogenesis.

Recent genomic analyses of the two sequenced strains F. nucleatum subsp. nucleatum ATCC 25586 and F. nucleatum subsp. vincentii ATCC 49256 suggested that the major protein secretion systems were absent. However, such a paucity of protein secretion systems is incongruous with F. nucleatum pathogenesis. Moreover, the presence of one or more such systems has been described for every other Gram-negative organism sequenced to date. In this investigation, the question of protein secretion in F. nucleatum was revisited. In the current study, the absence in F. nucleatum of a twin-arginine translocation system (TC #2.A.64.), a Type III secretion system (TC #3.A.6.), a Type IV secretion system (TC #3.A.7.) and a chaperone/usher pathway (TC #1.B.11.) was confirmed. However, contrary to previous findings, our investigations indicated that a Type I protein secretion system was also absent from F. nucleatum. In contrast, members of the holin family (TC #1.E) and the machinery required for a Type 4 piliation/fimbriation system (TC #3.A.15.2.) were identified using a variety of bioinformatic tools. Furthermore, a complete range of proteins resembling members of the Type V secretion pathway, i.e., the Type Va (autotransporter; TC #1.B.12.), Type Vb (two-partner secretion system; TC #1.B.20.) and Type Vc (YadA-like trimeric autotransporter; TC #1.B.42.), was found. This work provides new insight into the protein secretion and virulence mechanisms of F. nucleatum.

Amino Acid Motifs↗