Porphyromonas gingivalis Virulence in a Drosophila melanogaster Model

Abstract

Porphyromonas gingivalis has been implicated in the etiology of adult periodontitis. In this study, we examined the viability of Drosophila melanogaster as a new model for examining P. gingivalis-host interactions. P. gingivalis (W83) infection of Drosophila resulted in a systemic infection that killed in a dose-dependent manner. Differences in the virulence of several clinically prevalent P. gingivalis strains were observed in the Drosophila killing model, and the results correlated well with studies in mammalian infection models and human epidemiologic studies. P. gingivalis pathobiology in Drosophila did not result from uncontrolled growth of the bacterium in the Drosophila hemolymph (blood) or overt damage to Drosophila tissues. P. gingivalis killing of Drosophila was multifactorial, involving several bacterial factors that are also involved in virulence in mammals. The results from this study suggest that many aspects of P. gingivalis pathogenesis in mammals are conserved in Drosophila, and thus the Drosophila killing model should be useful for characterizing P. gingivalis-host interactions and, potentially, polymicrobe-host interactions.Porphyromonas gingivalis is a Gram-negative, obligate anaerobe that has been strongly implicated in the etiology of adult (chronic) periodontitis (21, 29), a destructive disease that affects the gums and supporting structures of the teeth. P. gingivalis-host interactions have previously been studied using several animal models, the most common of which are murine models (5,7,18,20,28), including an abscess model (39), a subcutaneous chamber model (24), and a periodontal bone loss model (41). Studies performed using murine models have demonstrated that P. gingivalis strains vary in their ability to cause periodontal bone loss (20, 40) and soft tissue destruction and death (28,43,56) and that strain W83 is highly virulent relative to many other strains of P. gingivalis (28,43,56). Murine models have also been used to identify P. gingivalis components that are important for pathogenesis (25,43,51,59) and to characterize the host response to P. gingivalis infection (6,11,31,35).The fruit fly, Drosophila melanogaster, has been well established as a nonmammalian model for studying host-pathogen interactions (1,17,52,55,63). Drosophila relies solely on an innate immune response to combat invading microbes, and this immune response strongly parallels the mammalian innate immune response (47,48). Like the mammalian innate immune response, Drosophila uses pattern recognition receptors to detect conserved microbial motifs on invading microbes, and the flies activate an immune response that is specific for the type of invading microbe. The absence of an adaptive immune response makes Drosophila useful for studying the interactions between microbes and the host innate immune response, in isolation. Numerous tools exist for the genetic manipulation of Drosophila, and these have been used to generate thousands of transgenic and mutant lines, including lines useful for identifying host fac...

Zebrafish as a new model to study effects of periodontal pathogens on cardiovascular diseases

“…A similar dose-dependent disease effect has been previously observed using a Drosophila melanogaster infection model albeit via a non-systemic route34. In addition, we observed extensive damage to the heart and surrounding tissue associated with pericardial oedemas.…”

Porphyromonas gingivalis-Host Interactions in aDrosophila melanogasterModel

“…Schneider et al suggested that Eiger signaling induced upon infection by some intracellular bacteria, which does not help fight infection, results in lethality via mechanisms that may be directly toxic or energetically wasteful (66). As heat-killed P. gingivalis kills Drosophila as readily as live P. gingivalis (37), nullification of the Imd pathway by the P. gingivalis capsule likely involves mechanisms that do not require bacterial viability. This study demonstrated that the C3/␣ 2 M superfamily proteins Tep II and Tep IV are involved in the Drosophila immune response against P. gingivalis infection.…”

“…We recently developed a Drosophila melanogaster killing model for examining P. gingivalis-host interactions (37), and in the current study the killing model was used to characterize the host response to P. gingivalis infection. The Drosophila model has been widely used to examine the host responses to many other bacterial pathogens.…”

“…We have recently developed a Drosophila killing model for examining P. gingivalis-host interactions (37). We observed that P. gingivalis is pathogenic in Drosophila and that differences in the virulence of P. gingivalis strains can be observed with the Drosophila killing model.…”

Study of Porphyromonas gingivalis in periodontal diseases: A systematic review and meta-analysis

“…The pathogenicity of P. gingivalis has been investigated in a variety of experimental animal models such as rat, mouse, rabbit, drosophila, and cell models, showing complicated mechanisms of P. gingivalis -host interplay in the expansion of periodontal diseases (15)(16)(17)(18)(19).…”