Mixed Red-Complex Bacterial Infection in Periodontitis

The red complex, which includes Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia (formerly Bacteroides forsythus), are recognized as the most important pathogens in adult periodontal disease. These bacteria are usually found together in periodontal pockets, suggesting that they may cause destruction of the periodontal tissue in a cooperative manner. This article discusses the interspecies pathogenic interactions within the red complex. 1. Introduction Periodontal diseases are polymicrobial immune-inflammatory infectious diseases that can lead to the destruction of periodontal ligaments and adjacent supportive alveolar bone. The subgingival plaque contains more than 700 bacterial species, and some of these microorganisms have been shown to be responsible for initiation/progression of periodontal diseases [1, 2]. The red complex, which includes Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia (formerly Bacteroides forsythus), encompasses the most important pathogens in adult periodontal disease [3]. Additionally, Fusobacterium nucleatum, Prevotella species, Eikenella corrodens, Peptostreptococcus micros, and Campylobacter rectus are increased in deep periodontal pockets and are implicated as possible periodontopathogens [1–4]. These bacteria are not usually found alone, but in combination in the periodontal pockets, suggesting that some bacteria may cause destruction of the periodontal tissue in a cooperative manner [5]. Studies using animal models have reported the synergistic pathogenicity of mixed infections with P. gingivalis-T. denticola, P. gingivalis-F. nucleatum, P. gingivalis-T. forsythia, P. gingivalis-Aggregatibacter actinomycetemcomitans, F. nucleatum-T. forsythia, and P. gingivalis-T. denticola-T. forsythia [6–11]. Furthermore, coaggregation, nutrient effects, and modulation of virulence factors by periodontopathogens or by interspecies interactions between periodontopathogenic and nonpathogenic organisms have been reported to contribute to oral microbial pathogenesis [12]. This paper focuses on interspecies pathogenic interactions within the red complex, in particular the combinations of P. gingivalis-T. forsythia, P. gingivalis-T. denticola, and P. gingivalis-T. forsythia-T. denticola. Potential therapies using normal inhabitants of the oral microbiota that have an antagonistic relationship with the red complex are discussed. 2. P. gingivalis and T. forsythia P. gingivalis possesses many virulence factors, such as fimbriae, lipopolysaccharides, and proteases [13–15]. The arg-gingipain (Rgp) and