Polymicrobial synergy within oral biofilm promotes invasion of dendritic cells and survival of consortia members

Abstract

Years of human microbiome research have confirmed that microbes rarely live or function alone, favoring diverse communities. Yet most experimental host-pathogen studies employ single species models of infection. Here, the influence of three-species oral microbial consortium on growth, virulence, invasion and persistence in dendritic cells (DCs) was examined experimentally in human monocyte-derived dendritic cells (DCs) and in patients with periodontitis (PD). Cooperative biofilm formation by Streptococcus gordonii, Fusobacterium nucleatum and Porphyromonas gingivalis was documented in vitro using growth models and scanning electron microscopy. Analysis of growth rates by species-specific 16s rRNA probes revealed distinct, early advantages to consortium growth for S. gordonii and F. nucleatum with P. gingivalis, while P. gingivalis upregulated its short mfa1 fimbriae, leading to increased invasion of DCs. F. nucleatum was only taken up by DCs when in consortium with P. gingivalis. Mature consortium regressed DC maturation upon uptake, as determined by flow cytometry. Analysis of dental plaques of PD and healthy subjects by 16s rRNA confirmed oral colonization with consortium members, but DC hematogenous spread was limited to P. gingivalis and F. nucleatum. Expression of P. gingivalis mfa1 fimbriae was increased in dental plaques and hematogenous DCs of PD patients. P. gingivalis in the consortium correlated with an adverse clinical response in the gingiva of PD subjects. In conclusion, we have identified polymicrobial synergy in a three-species oral consortium that may have negative consequences for the host, including microbial dissemination and adverse peripheral inflammatory responses.

Antimicrobial activities of mouthwashes obtained from various combinations of Elettaria cardamomum Maton., Lavandula angustifolia Mill. and Salvia triloba L. essential oils

“…Many antimicrobials and other strategies have been approved for oral and dental infections (Allaker & Ian Douglas, 2015). Nonetheless, the majority of the oral bacterial infections are polymicrobial in nature (El-Awady et al, 2019). Thus, the combination of antimicrobial molecules is essential to eliminate the polymicrobial infection.…”

Porphyromonas gingivalis, a Long-Range Pathogen: Systemic Impact and Therapeutic Implications

“…However, in the case of periodontal disease, it promotes the growth of keystone pathogens due to gingival inflammatory exudate being a rich source of nutrients [ 9 ]. Keystone pathogens, such as Porphyromonas gingivalis ( P. gingivalis ), facilitate the subversion of the host immune response through polymicrobial synergy allowing for the growth of both themselves and other dysbiotic species [ 10 , 11 , 12 ]. Polymicrobial synergy within the pathogenic oral biofilm is critical for the establishment and spread of periodontal disease.…”

“…Polymicrobial synergy within the pathogenic oral biofilm is critical for the establishment and spread of periodontal disease. It has been demonstrated in vitro that there is a cooperative biofilm formation involving Streptococcus gordonii , Fusobacterium nucleatum ( F. nucleatum ) and P. gingivalis [ 12 ]. When cocultured, these bacteria elicited extensive changes on each other’s biochemical signatures to support cohabitation within the biofilm [ 13 ].…”

A Novel Small Molecule, 1,3-di-m-tolyl-urea, Inhibits and Disrupts Multispecies Oral Biofilms

“…Therefore, S. gordonii, P. gingivalis, F. nucleatum and A. actinomycetemcomitans exhibit excellent synergistic interactions, forming a well-organized biofilm community [ 19 , 20 ]. Overall, the virulence and the pathogenic potential of biofilms is a collective result of inter-species communication and host–microbe interactions [ 15 , 21 , 22 ]…”