Ecological Dynamics of Broad- and Narrow-Host-Range Viruses Infecting the Bloom-Forming Toxic Cyanobacterium Microcystis aeruginosa

1. Harke MJ, Steffen MM, Gobler CJ, Otten TG, Wilhelm SW, Wood SA, Paerl

HW. 2016. A review of the global ecology, genomics, and biogeography

of the toxic cyanobacterium, Microcystis spp. Harmful Algae 54:4–20.

https://doi.org/10.1016/j.hal.2015.12.007.

2. MacKintosh C, Beattie KA, Klumpp S, Cohen P, Codd GA. 1990. Cyanobacterial microcystin-LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants. FEBS Lett 264:

187–192. https://doi.org/10.1016/0014-5793(90)80245-E.

3. Nishiwaki-Matsushima R, Ohta T, Nishiwaki S, Suganuma M, Kohyama K,

Ishikawa T, Carmichael WW, Fujiki H. 1992. Liver tumor promotion by the

cyanobacterial cyclic peptide toxin microcystin-LR. J Cancer Res Clin

Oncol 118:420–424. https://doi.org/10.1007/BF01629424.

4. Yoshizawa S, Matsushima R, Watanabe MF, Harada K, Ichihara A, Carmichael

WW, Fujiki H. 1990. Inhibition of protein phosphatases by microcystis and

nodularin associated with hepatotoxicity. J Cancer Res Clin Oncol 116:

609–614. https://doi.org/10.1007/BF01637082.

5. Stewart I, Seawright AA, Shaw GR. 2008. Cyanobacterial poisoning in livestock, wild mammals and birds–an overview. Adv Exp Med Biol 619:

613–637. https://doi.org/10.1007/978-0-387-75865-7_28.

6. Azevedo SMF, Carmichael WW, Jochimsen EM, Rinehart KL, Lau S, Shaw GR,

Eaglesham GK. 2002. Human intoxication by microcystins during renal dialysis treatment in Caruaru-Brazil. Toxicology 181–182:441–446. https://doi

.org/10.1016/s0300-483x(02)00491-2.

7. WHO. 2003. Cyanobacterial toxins: microcystin-LR in drinking water. Background document for preparation of WHO guidelines for drinking-water

quality. World Health Organization, Geneva, Switzerland.

8. Dick GJ, Duhaime MB, Evans JT, Errera RM, Godwin CM, Kharbush JJ,

Nitschky HS, Powers MA, Vanderploeg HA, Schmidt KC, Smith DJ, Yancey CE,

Zwiers CC, Denef VJ. 2021. The genetic and ecophysiological diversity of

February 2023 Volume 89 Issue 2

9.

10.

11.

12.

13.

14.

15.

Microcystis. Environ Microbiol 23:7278–7313. https://doi.org/10.1111/1462

-2920.15615.

Makarova KS, Wolf YI, Snir S, Koonin EV. 2011. Defense islands in bacterial

and archaeal genomes and prediction of novel defense systems. J Bacteriol 193:6039–6056. https://doi.org/10.1128/JB.05535-11.

Koonin EV, Makarova KS, Wolf YI. 2017. Evolutionary genomics of defense

systems in archaea and bacteria. Annu Rev Microbiol 71:233–261. https://

doi.org/10.1146/annurev-micro-090816-093830.

Papoulis SE, Wilhelm SW, Talmy D, Zinser ER. 2021. Nutrient loading and viral memory drive accumulation of restriction modification systems in

bloom-forming cyanobacteria. mBio 12:e0087321. https://doi.org/10.1128/

mBio.00873-21.

Kuno S, Yoshida T, Kaneko T, Sako Y. 2012. Intricate interactions between

the bloom-forming cyanobacterium Microcystis aeruginosa and foreign

genetic elements, revealed by diversified clustered regularly interspaced

short palindromic repeat (CRISPR) signatures. Appl Environ Microbiol 78:

5353–5360. https://doi.org/10.1128/AEM.00626-12.

Kuno S, Sako Y, Yoshida T. 2014. Diversification of CRISPR within coexisting

genotypes in a natural population of the bloom-forming cyanobacterium

Microcystis aeruginosa. Microbiology (Reading) 160:903–916. https://doi

.org/10.1099/mic.0.073494-0.

Yang C, Lin F, Li Q, Li T, Zhao J. 2015. Comparative genomics reveals diversified CRISPR-Cas systems of globally distributed Microcystis aeruginosa,

a freshwater bloom-forming cyanobacterium. Front Microbiol 6:394.

https://doi.org/10.3389/fmicb.2015.00394.

Yoshida T, Takashima Y, Tomaru Y, Shirai Y, Takao Y, Hiroishi S, Nagasaki

K. 2006. Isolation and characterization of a cyanophage infecting the toxic

cyanobacterium Microcystis aeruginosa. Appl Environ Microbiol 72:

1239–1247. https://doi.org/10.1128/AEM.72.2.1239-1247.2006.

10.1128/aem.02111-22

Downloaded from https://journals.asm.org/journal/aem on 28 February 2023 by 54.66.17.246.

ACKNOWLEDGMENTS

This work was supported by Grants-in Aids for Scientific Research (S) (no. 21H05057) and (B)

(no. 17H03850) from the Japan Society for the Promotion of Science (JSPS). This work was also

partly supported by The Canon Foundation (no. 203143100025), JSPS Scientific Research on

Innovative Areas (no. 16H06437), and the Bilateral Open Partnership Joint Research Project

(Japan-Lithuania Research Cooperative Program) “Research on prediction of environmental

change in Baltic Sea based on comprehensive metagenomic analysis of microbial viruses.”

We declare that the research was conducted in the absence of any commercial or

financial relationships that could be construed as a potential conflict of interest.

D.M. contributed to experiments and samplings, manuscript preparation, experimental

design, and results discussion. N.Y. mainly conducted experiments and part of the in silico

analysis. S.N. and A.S. supported the sampling and experiments. Y.S. contributed to

manuscript discussion and revision. T.Y. contributed to the experimental design, results

discussion, manuscript revision, and overall support for this study.

Temporal Change in Broad-Host-Range Microcystis Virus

February 2023 Volume 89 Issue 2

31.

32.

33.

34.

35.

36.

37.

38.

39.

40.

41.

42.

43.

44.

45.

a bloom dominated by Microcystis spp. in Western Lake Erie attributed to

a novel cyanophage. Appl Environ Microbiol 86:e01397-20. https://doi

.org/10.1128/AEM.01397-20.

Kimura S, Uehara M, Morimoto D, Yamanaka M, Sako Y, Yoshida T. 2018.

Incomplete selective sweeps of Microcystis population detected by the

leader-end CRISPR fragment analysis in a natural pond. Front Microbiol 9:

425. https://doi.org/10.3389/fmicb.2018.00425.

Kimura S, Yoshida T, Hosoda N, Honda T, Kuno S, Kamiji R, Hashimoto R,

Sako Y. 2012. Diurnal infection patterns and impact of Microcystis cyanophages in a Japanese pond. Appl Environ Microbiol 78:5805–5811. https://

doi.org/10.1128/AEM.00571-12.

Otsuka S, Suda S, Li R, Watanabe M, Oyaizu H, Matsumoto S, Watanabe

MM. 1999. Phylogenetic relationships between toxic and non-toxic strains

of the genus Microcystis based on 16S to 23S internal transcribedspacer

sequence. FEMS Microbiol Lett 172:15–21. https://doi.org/10.1111/j.1574

-6968.1999.tb13443.x.

Tillett D, Neilan BA. 2000. Xanthogenate nucleic acid isolation from cultured and environmental cyanobacteria. J Phycol 36:251–258. https://doi

.org/10.1046/j.1529-8817.2000.99079.x.

Yoshida M, Yoshida T, Takashima Y, Kondo R, Hiroishi S. 2005. Genetic diversity of the toxic cyanobacterium Microcystis in Lake Mikata. Environ

Toxicol 20:229–234. https://doi.org/10.1002/tox.20102.

Yoshida M, Yoshida T, Satomi M, Takashima Y, Hosoda N, Hiroishi S. 2008.

Intra-specific phenotypic and genotypic variation in toxic cyanobacterial

Microcystis strains. J Appl Microbiol 105:407–415. https://doi.org/10.1111/j

.1365-2672.2008.03754.x.

Rognes T, Flouri T, Nichols B, Quince C, Mahé F. 2016. VSEARCH: a versatile open source tool for metagenomics. PeerJ 4:e2584. https://doi.org/

10.7717/peerj.2584.

Bolger AM, Lohse M, Usadel B. 2014. Trimmomatic: a flexible trimmer for

Illumina sequence data. Bioinformatics 30:2114–2120. https://doi.org/10

.1093/bioinformatics/btu170.

Katoh K, Misawa K, Kuma K-i, Miyata T. 2002. MAFFT: a novel method for

rapid multiple sequence alignment based on fast Fourier transform. Nucleic

Acids Res 30:3059–3066. https://doi.org/10.1093/nar/gkf436.

Capella-Gutiérrez S, Silla-Martínez JM, Gabaldón T. 2009. trimAl: a tool for

automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics 25:1972–1973. https://doi.org/10.1093/bioinformatics/btp348.

Stamatakis A. 2006. RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Bioinformatics

22:2688–2690. https://doi.org/10.1093/bioinformatics/btl446.

Langmead B, Salzberg SL. 2012. Fast gapped-read alignment with Bowtie

2. Nat Methods 9:357–359. https://doi.org/10.1038/nmeth.1923.

Robinson TJ, Thorvaldsdóttir H, Winckler W, Guttman M, Lander SE, Getz G,

Mesirov PJ. 2011. Integrative genomics viewer. Nat Biotechnol 29:24–26.

https://doi.org/10.1038/nbt.1754.

Kimura S, Sako Y, Yoshida T. 2013. Rapid Microcystis cyanophage gene

diversification revealed by long and short-term genetic analyses of the

tail sheath gene in a natural pond. Appl Environ Microbiol 79:2789–2795.

https://doi.org/10.1128/AEM.03751-12.

Yoshida M, Yoshida T, Takashima Y, Hosoda N, Hiroishi S. 2007. Dynamics

of microcystin-producing and non-microcystin-producing Microcystis

populations is correlated with nitrate concentration in a Japanese lake.

FEMS Microbiol Lett 266:49–53. https://doi.org/10.1111/j.1574-6968.2006

.00496.x.

10.1128/aem.02111-22

Downloaded from https://journals.asm.org/journal/aem on 28 February 2023 by 54.66.17.246.

16. Ou T, Li S, Liao X, Zhang Q. 2013. Cultivation and characterization of the

MaMV-DC cyanophage that infects bloom-forming cyanobacterium Microcystis aeruginosa. Virol Sin 28:266–271. https://doi.org/10.1007/s12250-013

-3340-7.

17. Naknaen A, Suttinun O, Surachat K, Khan E, Pomwised R. 2021. A novel

jumbo phage PhiMa05 inhibits harmful Microcystis sp. Front Microbiol 12:

660351. https://doi.org/10.3389/fmicb.2021.660351.

18. Jin H, Jiang YL, Yang F, Zhang JT, Li WF, Zhou K, Ju J, Chen Y, Zhou CZ.

2019. Capsid structure of a freshwater cyanophage Siphoviridae Mic1.

Structure 27:1508–1516.e3. https://doi.org/10.1016/j.str.2019.07.003.

19. Lin W, Li D, Sun Z, Tong Y, Yan X, Wang C, Zhang X, Pei G. 2020. A novel

freshwater cyanophage vB_MelS-Me-ZS1 infecting bloom-forming cyanobacterium Microcystis elabens. Mol Biol Rep 47:7979–7989. https://doi

.org/10.1007/s11033-020-05876-8.

20. Watkins SC, Smith JR, Hayes PK, Watts JEM. 2014. Characterisation of host

growth after infection with a broad-range freshwater cyanopodophage.

PLoS One 9:e87339-8. https://doi.org/10.1371/journal.pone.0087339.

21. Cai R, Li D, Lin W, Qin W, Pan L, Wang F, Qian M, Liu W. 2022. Genome

sequence of the novel freshwater Microcystis cyanophage Mwe-Yong11121. Arch Virol 167:2371–2376. https://doi.org/10.1007/s00705-022-05542-3.

22. Wang F, Li D, Cai R, Pan L, Zhou Q, Liu W, Qian M, Tong Y. 2022. A Novel

freshwater cyanophage Mae-Yong1326-1 infecting bloom-forming cyanobacterium Microcystis aeruginosa. Viruses 14:2051. https://doi.org/10

.3390/v14092051.

23. Morimoto D, Tominaga K, Nishimura Y, Yoshida N, Kimura S, Sako Y,

Yoshida T. 2019. Cooccurrence of broad- and narrow-host-range viruses

infecting the bloom-forming toxic cyanobacterium Microcystis aeruginosa. Appl Environ Microbiol 85:e01170-19. https://doi.org/10.1128/AEM

.01170-19.

24. Yang F, Jin H, Wang X, Li Q, Zhang J, Cui N, Jiang Y-L, Chen Y, Wu Q-F,

Zhou C-Z, Li W-F. 2020. Genomic analysis of Mic1 reveals a novel freshwater long-tailed cyanophage. Front Microbiol 11:484. https://doi.org/10

.3389/fmicb.2020.00484.

25. Pound HL, Wilhelm SW. 2020. Tracing the active genetic diversity of Microcystis and Microcystis phage through a temporal survey of Taihu. PLoS One

15:e0244482-15. https://doi.org/10.1371/journal.pone.0244482.

26. Takashima Y, Yoshida T, Yoshida M, Shirai Y, Tomaru Y, Takao Y, Hiroishi S,

Nagasaki K. 2007. Development and application of quantitative detection

of cyanophages phylogenetically related to cyanophage Ma-LMM01 infecting Microcystis aeruginosa in fresh water. Microb Environ 22:207–213.

https://doi.org/10.1264/jsme2.22.207.

27. Yoshida M, Yoshida T, Kashima A, Takashima Y, Hosoda N, Nagasaki K,

Hiroishi S. 2008. Ecological dynamics of the toxic bloom-forming cyanobacterium Microcystis aeruginosa and its cyanophages in freshwater. Appl Environ Microbiol 74:3269–3273. https://doi.org/10.1128/AEM.02240-07.

28. Yoshida M, Yoshida T, Yoshida-Takashima Y, Kashima A, Hiroishi S. 2010.

Real-time PCR detection of host-mediated cyanophage gene transcripts

during infection of a natural Microcystis aeruginosa population. Microbes

Environ 25:211–215. https://doi.org/10.1264/jsme2.ME10117.

29. Stough JMA, Tang X, Krausfeldt LE, Steffen MM, Gao G, Boyer GL, Wilhelm

SW. 2017. Molecular prediction of lytic vs lysogenic states for Microcystis

phage: metatranscriptomic evidence of lysogeny during large bloom events.

PLoS One 12:e0184146. https://doi.org/10.1371/journal.pone.0184146.

30. McKindles KM, Manes MA, DeMarco JR, McClure A, McKay RM, Davis TW,

Bullerjahn GS. 2020. Dissolved microcystin release coincident with lysis of

Applied and Environmental Microbiology

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