Extracellular DNA secreted in yeast cultures is metabolism-specific and inhibits cell proliferation
Authors:Elisabetta de Alteriis1, Guido Incerti2, Fabrizio Cartenì3, Maria Luisa Chiusano3, Chiara Colantuono3, Emanuela Palomba4, Pasquale Termolino4, Francesco Monticolo3,5, Alfonso Esposito3, Giuliano Bonanomi3,6, Rosanna Capparelli3, Marco Iannaccone3,7, Alessandro Foscari2, Carmine Landi8, Palma Parascandola8, Massimo Sanchez9, Valentina Tirelli9, Bruna de Falco3, Virginia Lanzotti3 and Stefano Mazzoleni3,6
doi: 10.15698/mic2023.12.810
Volume 10, pp. 277 to 295, published 23/11/2023.
1 Department of Biology, University of Naples “Federico II”, Via Cinthia 26, 80126 Naples, Italy.
2 Department of Agricultural, Food, Environmental and Animal Sciences, University of Udine, via delle Scienze 206, 33100 Udine, Italy.
3 Department of Agricultural Sciences, University of Naples “Federico II”, via Università 100, 80055 Portici (NA), Italy.
4 Institute of Biosciences and Bioresources CNR, Via Università 133, 80055 Portici (NA), Italy.
5 Cutaneous Biology Research Center, Massachusetts General Hospital, Boston, MA, USA.
6 Task Force Microbiome – University of Naples “Federico II”.
7 Laboratory of Biotechnological Processes for Energy and Industry, ENEA, Via Anguillarese, 301, – 00123 Rome, Italy.
8 Department of Industrial Engineering, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, SA, Italy-
9 Istituto Superiore di Sanità (ISS) Core Facilities, Viale Regina Elena 299, 00161 Rome, Italy.
Keywords:
exDNA, eccDNA, self-DNA, 1H NMR, metabolomics, cell cycle.
Corresponding Author(s):
Conflict of interest statement:
EdA design and coordination of all experimental work, conceptual discussion, manuscript writing. GI conceptual discussion, data analysis (compari-son of sequences of exDNA and eccDNA, correlation of NMR spectral data). FC conceptual discussion, manu-script and figures preparation. MLC coordination of se-quencing and bioinformatic analysis. CC data analysis and figures of exDNA sequences. EP experimental work of inhibition tests, KEGG pathway analysis of exDNA se-quences. PT and AF DNA extraction and inhibition tests. GB and FM critical discussion and manuscript revision. RC critical discussion and cell cycle analysis. MI DNA am-plification and inhibition tests. CL and PP fed-batch cul-tures and bioreactors setting. MS and VT flow cytometric analysis and cell cycle data analysis. BdF HAP exDNA ex-traction and quantification. VL coordination of NMR analysis. SM team coordination, conceptual design of the work and manuscript preparation.
Please cite this article as:
Elisabetta de Alteriis, Guido Incerti, Fabrizio Cartenì, Maria Luisa Chiusano, Chiara Colantuono, Emanuela Palomba, Pasquale Termolino, Francesco Monticolo, Alfonso Esposito, Giuliano Bonanomi, Rosanna Capparelli, Marco Iannaccone, Alessandro Foscari, Carmine Landi, Palma Parascandola, Massimo Sanchez, Valentina Tirelli, Bruna de Falco, Virginia Lanzotti and Stefano Mazzoleni (2023). Extracellular DNA secreted in yeast cultures is metabolism specific and inhibits cell proliferation. Microbial Cell 10(12): 277-295. doi: 10.15698/mic2023.12.810
© 2023 de Alteriis et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Extracellular DNA (exDNA) can be actively released by living cells and different putative functions have been attributed to it. Further, homologous exDNA has been reported to exert species-specific inhibitory effects on several organisms. Here, we demonstrate by different experimental evidence, including 1H-NMR metabolomic fingerprint, that the growth rate decline in Saccharomyces cerevisiae fed-batch cultures is determined by the accumulation of exDNA in the medium. Sequencing of such secreted exDNA represents a portion of the entire genome, showing a great similarity with extrachromosomal circular DNA (eccDNA) already reported inside yeast cells. The recovered DNA molecules were mostly single strands and specifically associated to the yeast metabolism displayed during cell growth. Flow cytometric analysis showed that the observed growth inhibition by exDNA corresponded to an arrest in the S phase of the cell cycle. These unprecedented findings open a new scenario on the functional role of exDNA produced by living cells.