Unlearning Porphyromonas gingivalis pigments: toward an understanding of periodontal polymicrobial dysbiosis

Abstract

Polymicrobial dysbiosis is an important contributor to diseases. Periodontal diseases are a type of condition that arise from a disbiotic shift in the microbial community. Evidence suggests Porphyromonas gingivalis is a “keystone” pathogen that can manipulate the microbial community and trigger such a shift from homeostasis to dysbiosis. P. gingivalis is known to be a black pigmented bacterium which is attributed to the accumulation of haem on the cell surface. In this study, we discovered that P. gingivalis presents novel pigmentation phenotype composed of protoporphyrin IX (PPIX) and manganese PPIX (Mn-PPIX) under the conditions that mimic haemoglobin availability in periodontally healthy individuals. The ability of P. gingivalis to produce these novel pigments extracellularly involved chelatases. We found that P. gingivalis FetB, a homologue of cobalt chelatase CbiK, is a key chelatase involved in the production of Mn-PPIX. Recombinant apo FetB was shown to bind to various porphyrin compounds and possessed cobalt and manganese chelatase activities. The structure of FetB was determined using X-ray crystallography at 2.14 Å. The structure presents an α/β topology connected by a loop. The inactivation of the fetB gene resulted in growth retardation of P. gingivalis. Moreover, the fetB gene played an important role in a multispecies environment in vitro. When co-cultured with Fusobacterium nucleatum, the fetB deletion mutant was less competitive in growth compared to wild type P. gingivalis. Understanding the molecular mechanism of pigment production and the role of modified PPIX pigments in polymicrobial dysbiosis could shed light on novel treatment strategies to manage periodontal diseases. The novel pigmentation phenotype could also inform the future development of diagnostic tools in the clinical setting.