AUTHOR=Guo Yanyang , Wang Yu , Wang Yijin , Jin Yabing , Wang Chen 

TITLE=Heme Competition Triggers an Increase in the Pathogenic Potential of Porphyromonas gingivalis in Porphyromonas gingivalis-Candida albicans Mixed Biofilm

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.596459

DOI=10.3389/fmicb.2020.596459

ISSN=1664-302X

ABSTRACT=<p>As one of the main pathogens of periodontitis, <italic>Porphyromonas gingivalis</italic> often forms mixed biofilms with other bacteria or fungi under the gingiva, such as <italic>Candida albicans</italic>. Heme is an important iron source for <italic>P. gingivalis</italic> and <italic>C. albicans</italic> that supports their growth in the host. From the perspective of heme competition, this study aims to clarify that the competition for heme enhances the pathogenic potential of <italic>P. gingivalis</italic> during the interaction between <italic>P. gingivalis</italic> and <italic>C. albicans</italic>. <italic>Porphyromonas gingivalis</italic> single-species biofilm and <italic>P. gingivalis</italic>-<italic>C. albicans</italic> dual-species biofilm were established in a low- and high-heme environment. The results showed that the vitality of <italic>P. gingivalis</italic> was increased in the dual-species biofilm under the condition of low heme, and the same trend was observed under a laser confocal microscope. Furthermore, the morphological changes in <italic>P. gingivalis</italic> were observed by electron microscope, and the resistance of <italic>P. gingivalis</italic> in dual-species biofilm was stronger against the killing effect of healthy human serum and antibiotics. The ability of <italic>P. gingivalis</italic> to agglutinate erythrocyte was also enhanced in dual-species biofilm. These changes disappeared when heme was sufficient, which confirmed that heme competition was the cause of thepathogenicy change in <italic>P. gingivalis</italic>. Gene level analysis showed that <italic>P. gingivalis</italic> was in a superior position in the competition relationship by increasing the expression of heme utilization-related genes, such as HmuY, HmuR, HusA, and Tlr. In addition, the expression of genes encoding gingipains (Kgp, RgpA/B) was also significantly increased. They not only participate in the process of utilizing heme, but also are important components of the virulence factors of <italic>P. gingivalis</italic>. In conclusion, our results indicated that the pathogenic potential of <italic>P. gingivalis</italic> was enhanced by <italic>C. albicans</italic> through heme competition, which ultimately promoted the occurrence and development of periodontitis and, therefore, <italic>C. albicans</italic> subgingival colonization should be considered as a factor in assessing the risk of periodontitis.</p>