Transcriptomics-Aided Dissection of the Intracellular and Extracellular Roles of Microcystin in Microcystis aeruginosa PCC 7806

ABSTRACT Recent studies have provided evidence for both intracellular and extracellular roles of the potent hepatotoxin microcystin (MC) in the bloom-forming cyanobacterium Microcystis. Here, we surveyed transcriptomes of the wild-type strain M. aeruginosa PCC 7806 and the microcystin-deficient ΔmcyB mutant under low light conditions with and without the addition of external MC of the LR variant (MC-LR). Transcriptomic data acquired by microarray and quantitative PCR revealed substantial differences in the relative expression of genes of the central intermediary metabolism, photosynthesis, and energy metabolism. In particular, the data provide evidence for a lower photosystem I (PSI)-to-photosystem II (PSII) ratio and a more pronounced carbon limitation in the microcystin-deficient mutant. Interestingly, only 6% of the transcriptional differences could be complemented by external microcystin-LR addition. This MC signaling effect was seen exclusively for genes of the secondary metabolism category. The orphan polyketide synthase gene cluster IPF38-51 was specifically downregulated in response to external MC-LR under low light. Our data suggest a hierarchical and light-dependent cross talk of secondary metabolites and support both an intracellular and an extracellular role of MC in Microcystis.

[1]  E. Dittmann,et al.  Metabolomic analysis indicates a pivotal role of the hepatotoxin microcystin in high light adaptation of Microcystis. , 2015, Environmental microbiology.

[2]  Shawn R Campagna,et al.  Nutrients drive transcriptional changes that maintain metabolic homeostasis but alter genome architecture in Microcystis , 2014, The ISME Journal.

[3]  Samodha C Fernando,et al.  Secondary metabolite gene expression and interplay of bacterial functions in a tropical freshwater cyanobacterial bloom , 2014, The ISME Journal.

[4]  Sam P. Brown,et al.  Combinatorial quorum sensing allows bacteria to resolve their social and physical environment , 2014, Proceedings of the National Academy of Sciences.

[5]  J. Huisman,et al.  Genetic diversity of inorganic carbon uptake systems causes variation in CO2 response of the cyanobacterium Microcystis , 2013, The ISME Journal.

[6]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[7]  C. Gobler,et al.  Global Transcriptional Responses of the Toxic Cyanobacterium, Microcystis aeruginosa, to Nitrogen Stress, Phosphorus Stress, and Growth on Organic Matter , 2013, PloS one.

[8]  E. Dittmann,et al.  Environmental conditions that influence toxin biosynthesis in cyanobacteria. , 2013, Environmental microbiology.

[9]  T. Rohrlack,et al.  Putative Antiparasite Defensive System Involving Ribosomal and Nonribosomal Oligopeptides in Cyanobacteria of the Genus Planktothrix , 2013, Applied and Environmental Microbiology.

[10]  Elke Dittmann,et al.  Cyanobacterial toxins: biosynthetic routes and evolutionary roots. , 2013, FEMS microbiology reviews.

[11]  P. G. Arnison,et al.  Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. , 2013, Natural product reports.

[12]  Hans W. Paerl,et al.  Harmful Cyanobacterial Blooms: Causes, Consequences, and Controls , 2013, Microbial Ecology.

[13]  M. Hanaoka,et al.  RpaB, Another Response Regulator Operating Circadian Clock-dependent Transcriptional Regulation in Synechococcus elongatus PCC 7942* , 2012, The Journal of Biological Chemistry.

[14]  G. Boyer,et al.  Ecology: Healthy competition , 2011 .

[15]  M. Ikeuchi,et al.  Genetic Engineering of Group 2 σ Factor SigE Widely Activates Expressions of Sugar Catabolic Genes in Synechocystis Species PCC 6803* , 2011, The Journal of Biological Chemistry.

[16]  B. Ferrari,et al.  Comparative Protein Expression in Different Strains of the Bloom-forming Cyanobacterium Microcystis aeruginosa* , 2011, Molecular & Cellular Proteomics.

[17]  A. Kaplan,et al.  The Cyanobacterial Hepatotoxin Microcystin Binds to Proteins and Increases the Fitness of Microcystis under Oxidative Stress Conditions , 2011, PloS one.

[18]  J. Huisman,et al.  Reversal in competitive dominance of a toxic versus non-toxic cyanobacterium in response to rising CO2 , 2011, The ISME Journal.

[19]  J. Humbert,et al.  A Day in the Life of Microcystis aeruginosa Strain PCC 7806 as Revealed by a Transcriptomic Analysis , 2011, PloS one.

[20]  B. Neilan,et al.  NtcA from Microcystis aeruginosa PCC 7806 Is Autoregulatory and Binds to the Microcystin Promoter , 2010, Applied and Environmental Microbiology.

[21]  Robin Kirschbaum,et al.  Questions and answers , 2009, Diabetes, obesity & metabolism.

[22]  J. Humbert,et al.  Spatiotemporal changes in the genetic diversity of a bloom-forming Microcystis aeruginosa (cyanobacteria) population , 2009, The ISME Journal.

[23]  Y. Hihara,et al.  Mechanism of downregulation of photosystem I content under high-light conditions in the cyanobacterium Synechocystis sp. PCC 6803. , 2009, Microbiology.

[24]  H. Paerl,et al.  Climate change: a catalyst for global expansion of harmful cyanobacterial blooms. , 2009, Environmental microbiology reports.

[25]  Andrew C. Tolonen,et al.  Highly plastic genome of Microcystis aeruginosa PCC 7806, a ubiquitous toxic freshwater cyanobacterium , 2008, BMC Genomics.

[26]  Sabine Jähnichen,et al.  Impact of Inorganic Carbon Availability on Microcystin Production by Microcystis aeruginosa PCC 7806 , 2007, Applied and Environmental Microbiology.

[27]  A. Kaplan,et al.  Towards clarification of the biological role of microcystins, a family of cyanobacterial toxins. , 2007, Environmental microbiology.

[28]  M. Kanehisa,et al.  Positive Regulation of Sugar Catabolic Pathways in the Cyanobacterium Synechocystis sp. PCC 6803 by the Group 2 σ Factor SigE* , 2005, Journal of Biological Chemistry.

[29]  E. Dittmann,et al.  Distribution of microcystin-producing and non-microcystin-producing Microcystis sp. in European freshwater bodies: detection of microcystins and microcystin genes in individual colonies. , 2004, Systematic and applied microbiology.

[30]  Jean YH Yang,et al.  Bioconductor: open software development for computational biology and bioinformatics , 2004, Genome Biology.

[31]  J. Vaitomaa,et al.  Phylogenetic evidence for the early evolution of microcystin synthesis. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[32]  Terry Speed,et al.  Normalization of cDNA microarray data. , 2003, Methods.

[33]  S. Rabouille,et al.  Simulation of carbon reserve dynamics in Microcystis and its influence on vertical migration with Yoyo model. , 2003, Comptes rendus biologies.

[34]  L. R. Mur,et al.  Effects of Light on the Microcystin Content of Microcystis Strain PCC 7806 , 2003, Applied and Environmental Microbiology.

[35]  C. Mullineaux,et al.  The ycf27 genes from cyanobacteria and eukaryotic algae: distribution and implications for chloroplast evolution. , 2002, FEMS microbiology letters.

[36]  E. Dittmann,et al.  Consequences of impaired microcystin production for light-dependent growth and pigmentation of Microcystis aeruginosa PCC 7806 , 2001 .

[37]  M. Pfaffl,et al.  A new mathematical model for relative quantification in real-time RT-PCR. , 2001, Nucleic acids research.

[38]  E. Dittmann,et al.  Light and the Transcriptional Response of the Microcystin Biosynthesis Gene Cluster , 2000, Applied and Environmental Microbiology.

[39]  E. Dittmann,et al.  Role of Microcystins in Poisoning and Food Ingestion Inhibition of Daphnia galeata Caused by the Cyanobacterium Microcystis aeruginosa , 1999, Applied and Environmental Microbiology.

[40]  E. Dittmann,et al.  Insertional mutagenesis of a peptide synthetase gene that is responsible for hepatotoxin production in the cyanobacterium Microcystis aeruginosa PCC 7806 , 1997, Molecular microbiology.

[41]  N. Berndt,et al.  In vivo and in vitro binding of microcystin to protein phosphatases 1 and 2A. , 1995, Biochemical and biophysical research communications.

[42]  J. A. López del Val,et al.  Principal Components Analysis , 2018, Applied Univariate, Bivariate, and Multivariate Statistics Using Python.

[43]  P. Chomczyński,et al.  Feedback regulation of growth hormone (GH)-releasing hormone gene expression by GH in rat hypothalamus. , 1988, Molecular endocrinology.

[44]  R. H. Thomas,et al.  Buoyancy Regulation in a Strain of Microcystis , 1985 .

[45]  J. Waterbury,et al.  Generic assignments, strain histories, and properties of pure cultures of cyanobacteria , 1979 .