Dancing with the Stars: How Choreographed Bacterial Interactions Dictate Nososymbiocity and Give Rise to Keystone Pathogens, Accessory Pathogens, and Pathobionts

Abstract

Many diseases that originate on mucosal membranes ensue from the action of polymicrobial communities of indigenous organisms working in concert to disrupt homeostatic mechanisms. Multi-level physical and chemical communication systems among constituent organisms underlies polymicrobial synergy and dictates the community’s pathogenic potential or nososymbiocity, that is, disease arising from living together with a susceptible host. Functional specialization of community participants, often originating from metabolic co-dependence, has given rise to several newly appreciated designations within the commensal-to-pathogen spectrum. Accessory pathogens, while inherently commensal in a particular microenvironment, nonetheless enhance the colonization or metabolic activity of pathogens. Keystone pathogens (bacterial drivers or alpha-bugs) exert their influence at low abundance by modulating both the composition and levels of community participants and by manipulating host responses. Pathobionts (or bacterial passengers) exploit disrupted host homeostasis to flourish and promote inflammatory disease. In this review we will discuss how commensal or pathogenic properties of organisms are not intrinsic features, and have to be considered within the context of both the microbial community in which they reside and the host immune status.

Fungi at the Scene of the Crime: Innocent Bystanders or Accomplices in Oral Infections?

“…Most recently, it has been demonstrated that the attachment of P. gingivalis to C. albicans is facilitated by the virulence factor InlJ from the internalin protein family, which interacts with the C. albicans adhesin ALS3 [40]. Additionally, co-adhesion specific interactions were observed, where adhesive interactions between these pathogens appear to induce the type 9 secretion system of P. gingivalis, a system characterised as having an increased community pathogenicity [41].…”

The role of kinases and phosphatases in the pathobiology of porphyromonas gingivalis.

“…A secondary colonizer of subgingival plaque biofilms, P. gingivalis has an obligate requirement for iron in the form of hemin for growth, and possesses several hemin acquisition and storage systems with different activities and affinities [27]. P. gingivalis is best known for its role in periodontal diseases, as it is strongly implicated as a key periodontal pathogen in chronic and more severe manifestations of periodontal diseases [28][29][30][31]. P. gingivalis is a host-adapted opportunistic pathogen whose primary niche is the subgingival crevice of the oral cavity.…”

“…The dynamics at play in these polymicrobial microenvironments, both synergistic and antagonistic interactions, undoubtedly influence the overall pathogenicity of the resident biofilm. And as such, this directly impacts the "nososymbiocity" or disease causing potential of the biofilm as a whole [30]. This is a significant factor in treatment and prevention of human disease considering that the majority of skin and mucosal surfaces in humans are predominantly covered in bacterial biofilms.…”

“…In vivo support comes from experiments where mice infected with S. gordonii followed by P. gingivalis displayed significantly greater bone loss compared to mice infected with either organism alone [75]. recruited to periodontal pockets [30]. The second grouping of cytokines, the antiinflammatory cytokines, help to prevent any undesirable or harmful side effects of an exaggerated inflammatory reaction [164].…”

Characterization of Filifactor alocis and its immune evasion strategies employed against human neutrophils.

“…Nonetheless, the contribution to disease by these newly appreciated organisms has been overshadowed by the more readily cultivable species, and appreciation of their pathogenicity is just beginning to emerge (235,236). Filifactor alocis is a slow-growing gram-positive anaerobe which in culture-independent studies is consistently found at increased frequency and in elevated numbers at periodontal disease sites compared to healthy sites (2,44,54,57,58,60,61,63,64,234,237,238).…”