Genetic and molecular determinants of polymicrobial interactions in Fusobacterium nucleatum

Wu C, Chen Y-W, Scheible M, Chang C, Wittchen M, Lee JH, Luong TT, Tiner BL, Tauch A, Das A, Ton-That H (2021)
Proceedings of the National Academy of Sciences of the United States of America 118(23): e2006482118.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Wu, Chenggang; Chen, Yi-Wei; Scheible, Matthew; Chang, Chungyu; Wittchen, ManuelUniBi; Lee, Ju Huck; Luong, Truc T; Tiner, Bethany L; Tauch, AndreasUniBi; Das, Asis; Ton-That, Hung
Abstract / Bemerkung
A gram-negative colonizer of the oral cavity, Fusobacterium nucleatum not only interacts with many pathogens in the oral microbiome but also has the ability to spread to extraoral sites including placenta and amniotic fluid, promoting preterm birth. To date, however, the molecular mechanism of interspecies interactions-termed coaggregation-by F. nucleatum and how coaggregation affects bacterial virulence remain poorly defined. Here, we employed genome-wide transposon mutagenesis to uncover fusobacterial coaggregation factors, revealing the intertwined function of a two-component signal transduction system (TCS), named CarRS, and a lysine metabolic pathway in regulating the critical coaggregation factor RadD. Transcriptome analysis shows that CarR modulates a large regulon including radD and lysine metabolic genes, such as kamA and kamD, the expression of which are highly up-regulated in the DeltacarR mutant. Significantly, the native culture medium of DeltakamA or DeltakamD mutants builds up abundant amounts of free lysine, which blocks fusobacterial coaggregation with streptococci. Our demonstration that lysine-conjugated beads trap RadD from the membrane lysates suggests that lysine utilizes RadD as its receptor to act as a metabolic inhibitor of coaggregation. Lastly, using a mouse model of preterm birth, we show that fusobacterial virulence is significantly attenuated with the DeltakamA and DeltacarR mutants, in contrast to the enhanced virulence phenotype observed upon diminishing RadD (DeltaradD or DeltacarS mutant). Evidently, F. nucleatum employs the TCS CarRS and environmental lysine to modulate RadD-mediated interspecies interaction, virulence, and nutrient acquisition to thrive in the adverse environment of oral biofilms and extraoral sites.
Erscheinungsjahr
2021
Zeitschriftentitel
Proceedings of the National Academy of Sciences of the United States of America
Band
118
Ausgabe
23
Art.-Nr.
e2006482118
eISSN
1091-6490
Page URI
https://pub.uni-bielefeld.de/record/2955516

Zitieren

Wu C, Chen Y-W, Scheible M, et al. Genetic and molecular determinants of polymicrobial interactions in Fusobacterium nucleatum. Proceedings of the National Academy of Sciences of the United States of America. 2021;118(23): e2006482118.
Wu, C., Chen, Y. - W., Scheible, M., Chang, C., Wittchen, M., Lee, J. H., Luong, T. T., et al. (2021). Genetic and molecular determinants of polymicrobial interactions in Fusobacterium nucleatum. Proceedings of the National Academy of Sciences of the United States of America, 118(23), e2006482118. https://doi.org/10.1073/pnas.2006482118
Wu, C., Chen, Y. - W., Scheible, M., Chang, C., Wittchen, M., Lee, J. H., Luong, T. T., Tiner, B. L., Tauch, A., Das, A., et al. (2021). Genetic and molecular determinants of polymicrobial interactions in Fusobacterium nucleatum. Proceedings of the National Academy of Sciences of the United States of America 118:e2006482118.
Wu, C., et al., 2021. Genetic and molecular determinants of polymicrobial interactions in Fusobacterium nucleatum. Proceedings of the National Academy of Sciences of the United States of America, 118(23): e2006482118.
C. Wu, et al., “Genetic and molecular determinants of polymicrobial interactions in Fusobacterium nucleatum”, Proceedings of the National Academy of Sciences of the United States of America, vol. 118, 2021, : e2006482118.
Wu, C., Chen, Y.-W., Scheible, M., Chang, C., Wittchen, M., Lee, J.H., Luong, T.T., Tiner, B.L., Tauch, A., Das, A., Ton-That, H.: Genetic and molecular determinants of polymicrobial interactions in Fusobacterium nucleatum. Proceedings of the National Academy of Sciences of the United States of America. 118, : e2006482118 (2021).
Wu, Chenggang, Chen, Yi-Wei, Scheible, Matthew, Chang, Chungyu, Wittchen, Manuel, Lee, Ju Huck, Luong, Truc T, Tiner, Bethany L, Tauch, Andreas, Das, Asis, and Ton-That, Hung. “Genetic and molecular determinants of polymicrobial interactions in Fusobacterium nucleatum”. Proceedings of the National Academy of Sciences of the United States of America 118.23 (2021): e2006482118.

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