Extracellular DNA: A Missing Link in the Pathogenesis of Ectopic Mineralization

Shen, Minjuan; Jiao, Kai; Wang, Chenyu; Ehrlich, Hermann; Wan, Mei‐chen; Hao, Dongxiao; Li, Jing; Wan, Qian‐qian; Tonggu, Lige; Yan, Jianfei; Wang, Kaiyan; Ma, Yu‐Xuan; Chen, Ji Hua; Tay, Franklin R.; L, Niu

doi:10.1002/advs.202201368

Cited by 5 publications

(3 citation statements)

References 38 publications

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“…refs. 14 and 38 ) together with our observation that exogenous DNA is capable of inducing precipitation in cell-free medium would suggest the direct involvement of the negatively charged eDNA molecules in Ca 2+ recruitment and precipitation. At the same time, the contribution of microenvironment in ECM as well as involvement of amyloids in nucleation cannot be ruled out.…”

Section: Discussionmentioning

confidence: 69%

“…It can be supposed that in the case of B. cereus 4B this particular protein, in addition to its enzymatic function, may play the role in building ECM by amyloid-like structure formation. Besides the role in formation of the protein component of ECM, glyceraldehyde-3-phosphate dehydrogenase has been shown to act as a regulator of biofilm formation in a representative of B. cereus by triggering the formation of extracellular DNA 38 . In the calcium-and urea-free medium B4, we observed eDNA in relatively small quantities and only at the later stages of the growth.…”

Section: Discussionmentioning

confidence: 99%

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Matrix is everywhere: extracellular DNA is a link between biofilm and mineralization in Bacillus cereus planktonic lifestyle

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Егоров

Zabrodskaya

et al. 2023

npj Biofilms Microbiomes

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To date, the mechanisms of biomineralization induced by bacterial cells in the context of biofilm formation remain the subject of intensive studies. In this study, we analyzed the influence of the medium components on the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture. While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. Removal of eDNA, which was sensitive to treatment by DNase, did not affect other matrix components but resulted in disruption of cell network formation and a sixfold decrease in the precipitate yield. An experiment with a cell-free system confirmed the acceleration of mineral formation after the addition of exogenous salmon sperm DNA. The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. Taken together, our data showed that DNA in extracellular matrix is an essential factor for triggering the biomineralization in B. cereus planktonic culture.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Matrix is everywhere: extracellular DNA is a link between biofilm and mineralization in Bacillus cereus planktonic lifestyle

Иванова

Егоров

Zabrodskaya

et al. 2023

npj Biofilms Microbiomes

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“…Further tests are required to determine whether NETs function as nucleation sites for pathological mineralisation of calculi. These additional experiments will involve cryogenic transmission electron microscopy and molecular dynamics simulation 52,53 . The present work validated the hypothesis of NET-induced mineralisation in dental calculus only.…”

Section: Discussionmentioning

confidence: 99%

The critical role of neutrophil extracellular traps in pathological mineralization

Niu

2023

Preprint

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Neutrophil extracellular traps (NETs) are initially perceived as bioactive webs for trapping pathogens to limit the spread of infection. Neutrophils suicidally release NETs upon stimulation by pathogens and other non-infectious factors such as micro-crystals. Here, the authors demonstrate, using in vitro and in vivo calculus mineralisation models, that NETs function as nucleation sites for mineralisation of calculus. The NETs are usually cleared by nucleases derived from the host’s body fluids or immune system. However, bacteria in the calculus microenvironment are capable of transforming NETs from the more common nuclease-susceptible B-form into the nuclease-resistant Z-form. The crosstalk between infection and the host immune system results in the development of calculus. These findings indicate that calculus formation may be controlled by regulating the NET-DNA configuration. The use of chloroquine for converting NET-Z-DNA into NET-B-DNA represents a new therapeutic solution for reducing the prevalence and recurrence of calculus in populations who are susceptible to the development of these ectopic mineralisation entities.

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