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    Resumptive Streptococcus mutans Persisters Induced From Dimethylaminododecyl Methacrylate Elevated the Cariogenic Virulence by Up-Regulating the Quorum-Sensing and VicRK Pathway Genes

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    Author
    Lu, J.
    Cheng, L.
    Xu, H.H.K.
    Date
    2020
    Journal
    Frontiers in Microbiology
    Publisher
    Frontiers Media S.A.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3389/fmicb.2019.03102
    Abstract
    Bacterial persistence has become a worldwide health problem due to its ability to cause the recalcitrance and relapse of infections. The existence of bacterial persistence and their possible mechanisms have been widely reported. However, the following regrowth of persister cells is not clear although the awakening of dormant surviving persisters is the key to reinitialize bacterial infection. In this study, we investigated the growth character and cariogenic virulence during the recovery of Streptococcus mutans drug-tolerant persister cells induced by a novel quaternary ammonium: dimethylaminododecyl methacrylate (DMADDM). A remarkable lag phase was observed in S. mutans persisters when regrew at the first 24 h compared to normal cells. During the entire recovery state, persisters are metabolically active to increase the production of both water-soluble and water-insoluble glucan. The shortage of cell number in persisters resulted in the decrease of lactic acid production, but persisters gradually recovered the normal acid production ability after 72 h. The up-regulated expression of gtf and vicR was in line with comDE circuit and consistent with the virulence change during the regrowth stage. Our findings proved that lethal dosages of DMADDM induced drug-tolerant S. mutans persisters in biofilm, which had a prolonged lag phase and elevated cariogenic virulence during regrowth. The recovery and elevated virulence of persisters were regulated by quorum-sensing and VicRK pathway. This alarmed the elevated cariogenicity of persisters and highlighted the critical requirement for the drug-tolerance evaluation when developing new oral antimicrobial agents. To the best of our knowledge, we characterized the regrowth and cariogenic virulence variation of S. mutans persisters induced by quaternary ammonium for the first time. Our findings suggest that S. mutans persisters with the elevated cariogenic virulence during their regrowth stage highlighted the need of new strategy to overcome bacterial persistence. Meanwhile, the prolonged lag phase and the involvement of quorum-sensing system in the regrowth of S. mutans persisters may provide the potential targets. Copyright The Authors.
    Sponsors
    This study was supported by the National Natural Science Foundation of China grants 81870778 (BR), 81600858 (BR), 81870759 (LC), and 81430011 (XZ); the National Key Research Program of China (2017YFC0840100 and 2017YFC0840107 to LC); the Youth Grant of the Science and Technology Department of Sichuan Province, China, 2017JQ0028 (LC); and the Innovative Research Team Program of Sichuan Province (LC).
    Keyword
    anti-bacterial material
    cariogenic virulence
    dimethylaminododecyl methacrylate
    drug tolerance
    persister cells
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85079061199&doi=10.3389%2ffmicb.2019.03102&partnerID=40&md5=f2a7c814217c5ac72a613340760f4692; http://hdl.handle.net/10713/12015
    ae974a485f413a2113503eed53cd6c53
    10.3389/fmicb.2019.03102
    Scopus Count
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