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Chapter 4.2.2 : Heterotrophic Planktonic Microbes: Virus, Bacteria, Archaea, and Protozoa

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Abstract:

Marine planktonic microorganisms, including Bacteria, Archaea, Protozoans (Protists), and Viruses, all play critically important roles in marine ecosystems and global biogeochemical cycles. This chapter focuses on the non-photosynthetic marine plankton organisms, and summarizes information on what organisms are present in the ocean, their diversity, distributions, activities and interactions.

Citation: Fuhrman J, Caron D. 2016. Heterotrophic Planktonic Microbes: Virus, Bacteria, Archaea, and Protozoa, p 4.2.2-1-4.2.2-34. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch4.2.2
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Image of FIGURE 1
FIGURE 1

An early vision of the “microbial loop” and its connections to the classical grazing food chain via dissolved organic matter (DOM) flux and particulate trophic transfer, with viruses included as a side loop. Modified from ( ). Large gray arrows indicate the flow of organic carbon and energy into higher trophic levels of the food web, with recognition of the important roles for heterotrophic microbes (bacteria and protozoa) in this process. Large stippled arrows indicate the production of DOM via excretion and trophic interactions (not all groups are represented). Thin, dotted arrows indicate mineralization of major nutrients contained in organic matter respired by consumers. White arrows indicate bacteria lysis by viruses and DOM released by that process. doi:10.1128/9781555818821.ch4.2.2.f1

Citation: Fuhrman J, Caron D. 2016. Heterotrophic Planktonic Microbes: Virus, Bacteria, Archaea, and Protozoa, p 4.2.2-1-4.2.2-34. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch4.2.2
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Image of FIGURE 2
FIGURE 2

The three domains of life (upper left) as proposed by Woese et al. ( ), and a recent overview of modifications that have been proposed by Adl et al. ( ) to higher-level phylogentic groups within the eukaryotic component of the tree (lower right). Domains figure from Woese et al. ( ), eukaryotic tree figure from Adl et al. ( ). doi:10.1128/9781555818821.ch4.2.2.f2

Citation: Fuhrman J, Caron D. 2016. Heterotrophic Planktonic Microbes: Virus, Bacteria, Archaea, and Protozoa, p 4.2.2-1-4.2.2-34. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch4.2.2
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Image of Fig. 3.
Fig. 3.

(a, b) Plankton biomass in the Arabian Sea during the 1995 southwest monsoon (a) and intermonsoon period (b). Areas of the boxes indicate the relative magnitudes of the biomass in each category. Categories within the dashed boxes in a, b, c are composed of protozoa. Arrows indicate the direction of energy/material flow in the food web, thicker arrows depicting greater flow. Redrawn from ( ). (c) Depth-integrated biomass (mg/m) in the upper 100 m of the Sargasso Sea near Bermuda, and in the upper 200 m of the equatorial Pacific at 175°E. The width of the bars indicates the biomass in each size category. Heterotrophs have been separated by size class, while phytoplankton have not. Size classes delineated by the dotted box are comprised of protozoa. Redrawn from ( ). doi:10.1128/9781555818821.ch4.2.2.f3

Citation: Fuhrman J, Caron D. 2016. Heterotrophic Planktonic Microbes: Virus, Bacteria, Archaea, and Protozoa, p 4.2.2-1-4.2.2-34. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch4.2.2
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Image of FIGURE 4
FIGURE 4

Distribution of Bacteria, Euryarchaea, and marine Crenarchaea (recently renamed Thaumarchaea), along a transect in the North Atlantic Ocean, as measured by CARD FISH and expressed as % of total bacteria + archaea counts via DAPI stained epifluorescence, from Teira et al. ( ). Top panel shows station locations that are shown on the top of the lower three panels, with the distance in km reported along the transect from lower to higher station numbers. doi:10.1128/9781555818821.ch4.2.2.f4

Citation: Fuhrman J, Caron D. 2016. Heterotrophic Planktonic Microbes: Virus, Bacteria, Archaea, and Protozoa, p 4.2.2-1-4.2.2-34. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch4.2.2
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Image of FIGURE 5
FIGURE 5

Body plans and size ranges of protozoa. These micrographs depict amoeboid (a–g), flagellated (h–j), and ciliated (k–m) forms of protozoa. From Caron et al. ( ). Markers bars are 5 (i), 10 (h), 20 (c, j, l), 30 (a), 50 (k, m), 100 (b, f), 500 (d), and 1,000 (e, g) µm. doi:10.1128/9781555818821.ch4.2.2.f5

Citation: Fuhrman J, Caron D. 2016. Heterotrophic Planktonic Microbes: Virus, Bacteria, Archaea, and Protozoa, p 4.2.2-1-4.2.2-34. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch4.2.2
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Image of FIGURE 6
FIGURE 6

Marine viruses (upper left collage) viewed by transmission electron microscopy. These are cyanophages in the groups myoviridae (right and bottom), siphoviridae (left), and podoviridae (top). Scale bars represent 100 nm. From Sullivan ( ). Epifluorescence micrograph (lower left) of SYBR green I stained viruses (small fluorescing objects) and bacteria + archaea (large fluorescing objects). Depth distribution of virus and bacteria + archaea abundances, obtained by epifluorescence microscopy of SYBR Green stained cells, in the central San Pedro Basin, California (11 August 2000). doi:10.1128/9781555818821.ch4.2.2.f6

Citation: Fuhrman J, Caron D. 2016. Heterotrophic Planktonic Microbes: Virus, Bacteria, Archaea, and Protozoa, p 4.2.2-1-4.2.2-34. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch4.2.2
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Image of FIGURE 7
FIGURE 7

Modification of the microbial loop concept that incorporates the functional role of viruses. Export can be via predation or sinking. From Fuhrman ( ). doi:10.1128/9781555818821.ch4.2.2.f7

Citation: Fuhrman J, Caron D. 2016. Heterotrophic Planktonic Microbes: Virus, Bacteria, Archaea, and Protozoa, p 4.2.2-1-4.2.2-34. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch4.2.2
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Image of FIGURE 8
FIGURE 8

Meta-analysis of experimental studies that have compared rates of bacterial productivity (converted to population growth rate, units of d), with rates of bacterivory by phagotrophic protists (expressed as equivalent units of bacterial growth rate; d). The solid line indicates where measurements of bacterial removal by grazers were equal to measurements of bacterial production. Data redrawn from Sanders et al. ( ). doi:10.1128/9781555818821.ch4.2.2.f8

Citation: Fuhrman J, Caron D. 2016. Heterotrophic Planktonic Microbes: Virus, Bacteria, Archaea, and Protozoa, p 4.2.2-1-4.2.2-34. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch4.2.2
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Image of FIGURE 9
FIGURE 9

Microbial association network, showing co-occurrence patterns of near-surface planktonic microbes at the San Pedro Ocean Time Series, USC Microbial Observatory, sampled monthly for 3 years. This network shows only organisms and parameters directly correlated to cyanobacteria (green, ; pink, ). Circles, bacteria; V-shape, T4-like myoviruses; blue diamonds, protists; hexagons and squares, environmental parameters and processes (nutrients, salinity, chlorophyll [Chl_a], primary productivity [Prim_Prod]); solid lines, positive correlation as measured by local similarity analysis; dashed line, negative correlation; arrows point to correlations lagged by 1 month; data in Chow et al. 2013 ( ). Symbols sized to reflect relative abundances within each group. doi:10.1128/9781555818821.ch4.2.2.f9

Citation: Fuhrman J, Caron D. 2016. Heterotrophic Planktonic Microbes: Virus, Bacteria, Archaea, and Protozoa, p 4.2.2-1-4.2.2-34. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch4.2.2
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References

/content/book/10.1128/9781555818821.ch4.2.2
1. Calkins GN. 1901. Marine protozoa from Woods Hole. Bull Bur Fish 21:413468.
2. Fischer B. 1883. Bacteriologische Untersuchungen auf einer Reise nach Westindien. Zeitschr Hyg 1:421464.
3. Haeckel E,. 1887. Report on radiolaria collected by H.M.S. Challenger during the 1873–1876, pp 11760. In Thompson CW, Murray J (eds.), The Voyage of the HMS Challenger, vol 18. Her Majesty's Stationary Office, London.
4. Jannasch HW, Jones GE. 1959. Bacterial populations in sea water as determined by different methods of enumeration. Limnol Oceanogr 4:128139.[CrossRef]
5. Parsons TR, Strickland JDH. 1961. On the production of particulate organic carbon by heterotrophic processes in sea-water. Deep Sea Res 8:211222.[CrossRef]
6. Wright RT, Hobbie JE. 1966. Use of glucose and acetate by bacteria and algae in aquatic ecosystems. Ecology 47:447453.[CrossRef]
7. Beers JR, Stewart GL. 1969. Micro-zooplankton and its abundance relative to the larger zooplankton and other seston components. Mar Biol 4:182189.[CrossRef]
8. Fenchel T. 1967. The ecology of marine microbenthos. I. The quantitative importance of ciliates as compared with metazoans in various types of sediments. Ophelia 4:121137.[CrossRef]
9. Lighthart B. 1969. Planktonic and benthic bacteriovorous protozoa at eleven stations in Puget Sound and adjacent Pacific Ocean. Can J Fish Aquat Sci 26:299304.
10. Utermöhl H. 1958. Zur Vervollkommung der quantitativen phytoplankton-methodik. Mitt Int Ver Limnol 9:38.
11. Steele JH. 1974. The Structure of Marine Ecosystems. Harvard University Press, Cambridge, MA.
12. Pomeroy LR. 1974. The ocean's food web, a changing paradigm. Bioscience 24:499504.[CrossRef]
13. Andrews P, Williams PJL. 1971. Heterotrophic utilization of dissolved compounds in the sea. III. Measurements of the oxidation rates and concentrations of glucose and amino acids in sea water. J Mar Biol Assoc UK 51:111125.[CrossRef]
14. Williams PJL. 1981. Microbial contribution to overall marine plankton metabolism—direct measurements of respiration. Oceanolog Acta 4:359364.
15. Fenchel TM, Jorgensen BB,. 1977. Detritus food chains of aquatic ecosystems: the role of bacteria, pp 158. In Alexander M (ed.), Adv microb ecol, vol. 1. Plenum Press, New York, NY.
16. Francisco DE, Mah RA, Rabin AC. 1973. Acridine orange epifluorescence technique for counting bacteria in natural waters. Trans Am Microsc Soc 92:416421.[PubMed][CrossRef]
17. Hobbie JE, Daley RJ, Jasper S. 1977. Use of Nuclepore filters for counting bacteria by fluorescence microscopy. Appl Environ Microbiol 33:12251228.[PubMed]
18. Beers JR, Stewart GL. 1971. Micro-zooplankters in the plankton communities of the upper waters of the eastern tropical Pacific. Deep Sea Res 18:861883.
19. Caron DA. 1983. Technique for enumeration of heterotrophic and phototrophic nanoplankton, using epifluorescence microscopy, and comparison with other procedures. Appl Environ Microbiol 46:491498.[PubMed]
20. Haas LW. 1982. Improved epifluorescence microscopy for observing planktonic micro-organisms. Annls Inst Oceanogr 58:261266.
21. Sherr EB, Caron DA, Sherr BF,. 1993. Staining of heterotrophic protists for visualization via epifluorescence microscopy, pp 213227. In Kemp P, Sherr B, Sherr E, Cole J (eds.), Handbook of Methods in Aquatic Microbial Ecology. Lewis Publishers, Boca Raton, FL.
22. Montagnes DJS, Lynn DH,. 1993. A quantitative protargol stain (QPS) for ciliates and other protists, pp 229240. In Kemp PF, Sherr BF, Sherr EB, Cole JJ (eds.), Handbook of Methods in Aquatic Microbial Ecology. Lewis Publishers, Boca Raton, FL.
23. Hagström A, Larsson U, Horstedt P, Normark S. 1979. Frequency of dividing cells, a new approach to the determination of bacterial growth rates in aquatic environments. Appl Environ Microbiol 37:805812.[PubMed]
24. Fuhrman JA, Azam F. 1980. Bacterioplankton secondary production estimates for coastal waters of British Columbia, Antarctica, and California. Appl Environ Microbiol 39:10851095.[PubMed]
25. Fuhrman JA, Azam F. 1982. Thymidine incorporation as a measure of heterotrophic bacterioplankton production in marine surface waters: evaluation and field results. Mar Biol 66:109120.[CrossRef]
26. Kirchman Dl, K'Nees E, Hodson RE. 1985. Leucine incorporation and its potential as a measure of protein synthesis by bacteria in natural aquatic systems. Appl Environ Microbiol 49:599607.[PubMed]
27. Caron DA, Davis PG, Madin LP, Sieburth JM. 1982. Heterotrophic bacteria and bacterivorous protozoa in oceanic macroaggregates. Science 218:795797.[PubMed][CrossRef]
28. Fenchel T. 1982. Ecology of heterotrophic microflagellates. I. Some important forms and their functional morphology. Mar Ecol Prog Ser 8:211223.[CrossRef]
29. Sherr BF, Sherr EB, Berman T. 1982. Decomposition of organic detritus: a selective role for microflagellate protozoa. Limnol Oceanogr 27:765769.[CrossRef]
30. Capriulo GM, Carpenter EJ. 1980. Grazing by 35 to 202 µm micro-zooplankton in Long Island Sound. Mar Biol 56:319326.[CrossRef]
31. Heinbokel JF, Beers JR. 1979. Studies on the functional role of tintinnids in the Southern California Bight. III. Grazing impact of natural assemblages. Mar Biol 52:2332.[CrossRef]
32. Sherr BF, Sherr EB, Andrew TL, Fallon RD, Newell SY. 1986. Trophic interactions between heterotrophic Protozoa and bacterioplankton in estuarine water analyzed with selective metabolic inhibitors. Mar Ecol Prog Ser 32:169179.[CrossRef]
33. Stoecker DK, Capuzzo JM. 1990. Predation on protozoa: its importance to zooplankton. J Plankton Res 12:891908.[CrossRef]
34. Azam F, Fenchel T, Gray JG, Meyer-Reil LA, Thingstad T. 1983. The ecological role of water-column microbes in the sea. Mar Ecol Prog Ser 10:257263.[CrossRef]
35. DeLong EF, Taylor LT, Marsh TL, Preston CM. 1999. Visualization and enumeration of marine planktonic archaea and bacteria by using polyribonucleotide probes and fluorescent in situ hybridization. Appl Environ Microbiol 65:55545563.[PubMed]
36. Fuhrman JA, Ouverney CC. 1998. Marine microbial diversity studied via 16S rRNA sequences: cloning results from coastal waters and counting of native archaea with fluorescent single cell probes. Aq Ecol 32:315.[CrossRef]
37. Teira E, Reinthaler T, Pernthaler A, Pernthaler J, Herndl GJ. 2004. Combining catalyzed reporter deposition-fluorescence in situ hybridization and microautoradiography to detect substrate utilization by bacteria and archaea in the deep ocean. Appl Environ Microbiol 70:44114414.[PubMed][CrossRef]
38. Noble RT, Fuhrman JA. 1998. Use of SYBR Green I for rapid epifluorescence counts of marine viruses and bacteria. Aq Microb Ecol 14:113118.[CrossRef]
39. Porter KG, Feig YS. 1980. The use of DAPI for identifying and counting aquatic microflora. Limnol Oceanogr 25:943948.[CrossRef]
40. Velji MI, Albright LJ. 1986. Microscopic enumeration of attached marine bacteria of seawater, marine sediment, fecal matter, and kelp blade samples following pyrophosphate and ultrasound treatments. Can J Microbiol 32:121126.[CrossRef]
41. delGiorgio PA, Gasol JM, Vaque D, Mura P, Agusti S, Duarte CM. 1996. Bacterioplankton community structure: protists control net production and the proportion of active bacteria in a coastal marine community. Limnol Oceanogr 41:11691179.[CrossRef]
42. Monger BC, Landry MR. 1992. Size-selective grazing by heterotrophic nanoflagellates: an analysis using live-stained bacteria and dual-beam flow cytometry. Arch Hydrobiol Beih 37:173185.
43. Campbell L, Nolla HA, Vaulot D. 1994. The importance of prochlorococcus to community structure in the central north Pacific-Ocean. Limnol Oceanogr 39:954961.[CrossRef]
44. Ducklow HW,. 2000. Bacterial production and biomass in the oceans, pp 85120. In Kirchman DL (ed.), Microbial Ecology of the Oceans. Wiley-Liss, New York, NY.
45. Fuhrman JA, Ammerman JW, Azam F. 1980. Bacterioplankton in the coastal euphotic zone: distribution, activity, and possible relationships with phytoplankton. Mar Biol 60:201207.[CrossRef]
46. Simon M, Azam F. 1989. Protein content and protein synthesis rates of planktonic marine bacteria. Mar Ecol Prog Ser 51:201213.[CrossRef]
47. Caron DA, Lim EL, Kunze H, Cosper EM, Anderson DM,. 1989. Trophic interactions between nano- and microzooplankton and the “brown tide,” pp 265294. In Cosper EM, Bricelj VM, Carpenter EJ (eds.), Novel Phytoplankton Blooms: Causes and Impacts of Recurrent Brown Tides and Other Unusual Blooms, vol. 35. Springer, Berlin.
48. Agogue H, Brink M, Dinasquet J, Herndl GJ. 2008. Major gradients in putatively nitrifying and non-nitrifying Archaea in the deep North Atlantic. Nature 456:788791.[PubMed][CrossRef]
49. Schmidt JL, Deming JW, Jumars PA, Keil RG. 1998. Constancy of bacterial abundance in surficial marine sediments. Limnol Oceanogr 43:976982.[CrossRef]
50. Fuhrman JA, Eppley RW, Hagstrom A, Azam F. 1985. Diel variation in bacterioplankton, and related parameters in the Southern California Bight. Mar Ecol Prog Ser 27:920.[CrossRef]
51. Wikner J, Hagstrom A. 1991. Annual study of bacterioplankton community dynamics. Limnol Oceanogr 36:13131324.[CrossRef]
52. Carlson CA, Ducklow HW, Sleeter TD. 1996. Stocks and dynamics of bacterioplankton in the northwestern Sargasso Sea. Deep Sea Res 43:491515.[CrossRef]
53. Burney CM, Davis PG, Johnson KM, Sieburth JM. 1982. Diel relationships of microbial trophic groups and in situ dissolved carbohydrate dynamics in the Caribbean Sea. Mar Biol 67:311322.[CrossRef]
54. Gasol JM, Doval MD, Pinhassi J, Calderon-Paz JI, Guixa-Boixareu N, Vaque D, Pedros-Alio C. 1998. Diel variations in bacterial heterotrophic activity and growth in the northwestern Mediterranean Sea. Mar Ecol Prog Ser 164:107124.[CrossRef]
55. Hagström A, Pinhassi J, Zweifel UL. 2001. Marine bacterioplankton show bursts of rapid growth induced by substrate shifts. Aq Microb Ecol 24:109115.[CrossRef]
56. Fuhrman JA. 1987. Close coupling between release and uptake of dissolved free amino acids in seawater studied by an isotope dilution approach. Mar Ecol Prog Ser 37:4552.[CrossRef]
57. Pomeroy LR, Wiebe WJ, Deibel D, Thompson RJ, Rowe GT, Pakulski JD. 1991. Bacterial responses to temperature and substrate concentration during the Newfoundland spring bloom. Mar Ecol Prog Ser 75:143159.[CrossRef]
58. Eppley RW. 1972. Temperature and phytoplankton growth in the sea. Fish Bull 70:10631085.
59. Rose JM, Caron DA. 2007. Does low temperature constrain the growth rates of heterotrophic protists? Evidence and implications for algal blooms in cold water. Limnol Oceanogr 52:886895.[CrossRef]
60. Jansson J, Prosser J. 1997. Quantification of the presence and activity of specific microorganisms in nature. Mol Biotechnol 7:103120.[PubMed][CrossRef]
61. Bird DF, Kalff J. 1984. Empirical relationships between bacterial abundance and chlorophyll concentration in fresh and marine waters. Can J Fish Aquat Sci 41:10151023.[CrossRef]
62. Cole JJ, Findlay S, Pace ML. 1988. Bacterial production in fresh and saltwater ecosystems: a cross-system overview. Mar Ecol Prog Ser 43:110.[CrossRef]
63. Sanders RW, Caron DA, Berninger U-G. 1992. Relationships between bacteria and heterotrophic nanoplankton in marine and fresh water: an inter-ecosystem comparison. Mar Ecol Prog Ser 86:114.[CrossRef]
64. Fuhrman JA, Sleeter TD, Carlson CA, Proctor LM. 1989. Dominance of bacterial biomass in the Sargasso Sea and its ecological implications. Mar Ecol Prog Ser 57:207217.[CrossRef]
65. Roman MR, Caron DA, Kremer P, Lessard EJ, Madin LP, Malone TC, Napp JM, Peele ER, Youngbluth MJ. 1995. Spatial and temporal changes in the partitioning of organic carbon in the plankton community of the Sargasso Sea off Bermuda. Deep Sea Res 42:973992.[CrossRef]
66. Cho B, Azam F. 1990. Biogeochemical significance of bacterial biomass in the ocean's euphotic zone. Mar Ecol Prog Ser 63:253259.[CrossRef]
67. Sieracki ME, Haugen EM, Cucci TL. 1995. Overestimation of heterotrophic bacteria in the Sargasso Sea: direct evidence by flow and imaging cytometry. Deep Sea Res 42:13991409.[CrossRef]
68. Whittaker RH. 1969. New concepts of kingdoms of organisms. Science 163:150160.[PubMed][CrossRef]
69. Keeling PJ. 2013. The number, speed, and impact of plastid endosymbioses on eukaryotic evolution. Annu Rev Plant Biol 64:583607.[PubMed][CrossRef]
70. Burkholder JM, Glibert PM, Skelton HM. 2008. Mixotrophy, a major mode of nutrition for harmful algal species in eutrophic waters. Harmful Algae 8:7793.[CrossRef]
71. Hansen PJ. 2011. The role of photosynthesis and food uptake for the growth of marine mixotrophic dinoflagellates. J Euk Microbiol 58:203214.[PubMed][CrossRef]
72. Stoecker DK. 1999. Mixotrophy among dinoflagellates. J Euk Microbiol 46:397401.[CrossRef]
73. Skovgaard A. 1998. Role of chloroplast retention in a marine dinoflagellate. Aq Microb Ecol 15:293301.[CrossRef]
74. Caron DA,. 2000. Symbiosis and mixotrophy among pelagic microorganisms, pp 495523. In Kirchman DL (ed.), Microbial Ecology of the Oceans. Wiley-Liss, New York, NY.
75. Mitra A, Flynn KJ. 2010. Modelling mixotrophy in harmful algal blooms: more or less the sum of the parts? J Mar Systems 83:158169.[CrossRef]
76. Sanders RW. 1991. Mixotrophic protists in marine and freshwater ecosystems. J Protozool 38:7681.[CrossRef]
77. Stoecker DK. 1998. Conceptual models of mixotrophy in planktonic protists and some ecological and evolutionary implications. Eur J Protistol 34:281290.[CrossRef]
78. Woese CR, Kandler O, Wheelis ML. 1990. Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eukarya. Proc Natl Acad Sci 87:45764579.[PubMed][CrossRef]
79. Adl SM, Simpson AGB, Lane CE, Lukeš J, Bass D, Bowser SS, Brown MW, Burki F, Dunthorn M, Hampl V, Heiss A, Hoppenrath M, Lara E, le Gall L, Lynn DH, McManus H, Mitchell EAD, Mozley-Stanridge SE, Parfrey LW, Pawlowski J, Rueckert S, Shadwick L, Schoch CL, Smirnov A, Spiegel FW. 2012. The revised classification of eukaryotes. J Euk Microbiol 59:429514.[PubMed][CrossRef]
80. Caron DA, Countway PD, Jones AC, Kim DY, Schnetzer A. 2012. Marine protistan diversity. Ann Rev Mar Sci 4:467493.[PubMed][CrossRef]
81. Guillou L, Moon-van der Staay S-Y, Claustre H, Partensky F, Vaulot D. 1999. Diversity and abundance of Bolidophyceae (Heterokonta) in two oceanic regions. Appl Environ Microbiol 65:45284536.[PubMed]
82. Anderson OR. 1983. Radiolaria. Springer, New York, NY.
83. Swanberg NR, Harbison GR. 1980. The ecology of Collozoum longiforme, sp. nov., a new colonial radiolarian from the equatorial Atlantic Ocean. Deep Sea Res 27A:715732.[CrossRef]
84. Sieburth JM, Smetacek V, Lenz J. 1978. Pelagic ecosystem structure: heterotrophic compartments of the plankton and their relationship to plankton size fractions. Limnol Oceanogr 23:12561263.[CrossRef]
85. Worden AZ, Follows MJ, Giovannoni SJ, Wilken S, Zimmerman AE, Keeling PJ. 2015. Environmental science. Rethinking the marine carbon cycle: factoring in the multifarious lifestyles of microbes. Science 347:1257594.[PubMed][CrossRef]
86. Garrison DL, Gowing MM, Hughes MP, Campbell L, Caron DA, Dennett MR, Shalapyonok A, Olson RJ, Landry MR, Brown SL, Liu HB, Azam F, Steward GF, Ducklow HW, Smith DC. 2000. Microbial food web structure in the Arabian Sea: a US JGOFS study. Deep Sea Res II 47:13871422.[CrossRef]
87. Arenovski AL, Lim EL, Caron DA. 1995. Mixotrophic nanoplankton in oligotrophic surface waters of the Sargasso Sea may employ phagotrophy to obtain major nutrients. J Plankton Res 17:801820.[CrossRef]
88. Sanders RW, Gast RJ. 2011. Bacterivory by phototrophic picoplankton and nanoplankton in Arctic waters. FEMS Microbiol Ecol 82:242253; 10.1111/j.1574-6941.2011.01253.x:242-252.[PubMed][CrossRef] http://dx.doi.org/10.1111/j.1574-6941.2011.01253.x:242-252
89. Smalley GW, Coats DW, Adam EJ. 1999. A new method using fluorescent microspheres to determine grazing on ciliates by the mixotrophic dinoflagellate Ceratium furca. Aq Microb Ecol 17:167179.[CrossRef]
90. Unrein F, Gasol JM, Not F, Forn I, Massana R. 2014. Mixotrophic haptophytes are key bacterial grazers in oligotrophic coastal waters. ISME J 8:164176.[PubMed][CrossRef]
91. Bockstahler KR, Coats DW. 1993. Grazing of the mixotrophic dinoflagellate Gymnodinium sangiuneum on ciliate populations of Chesapeake Bay. Mar Biol 116:477487.[CrossRef]
92. Mitra A, Flynn KJ, Burkholder JM, Berge T, Calbet A, Raven JA, Granéli E, Glibert PM, Hansen PJ, Stoecker DK, Thingstad F, Tillmann U, Våge S, Wilken S, Zubkov MV. 2014. The role of mixotrophic protists in the biological carbon pump. Biogeosciences 11:9951005.[CrossRef]
93. Stoecker D, Taniguchi A, Michaels AE. 1989. Abundance of autotrophic, mixotrophic and heterotrophic planktonic ciliates in shelf and slope waters. Mar Ecol Prog Ser 50:241254.[CrossRef]
94. Crawford DW. 1989. Mesodinium rubrum: the phytoplankter that wasn't. Mar Ecol Prog Ser 58:161174.[CrossRef]
95. Esteban G, Fenchel T, Finlay BJ. 2010. Mixotrophy in ciliates. Protist 161:621641.[PubMed][CrossRef]
96. Johnson MD. 2011. Acquired phototrophy in ciliates: a review of cellular interactions and structural adaptations. J Euk Microbiol 58:185195.[PubMed][CrossRef]
97. Caron DA, Swanberg NR. 1990. The ecology of planktonic sarcodines. Rev Aq Sci 3:147180.
98. Decelle J, Probert I, Bittner L, Desdevises Y, Colin S, de Vargas C, Galí M, Simó R, Not F. 2012. An original mode of symbiosis in open ocean plankton. Proc Nat Acad Sci 109:1800018005.[PubMed][CrossRef]
99. Caron DA, Michaels AF, Swanberg NR, Howse FA. 1995. Primary productivity by symbiont-bearing planktonic sarcodines (acantharia, radiolaria, foraminifera) in surface waters near Bermuda. J Plankton Res 17:103129.[CrossRef]
100. Evans GT, Taylor FJR. 1980. Phytoplankton accumulation in Langmuir cells. Limnol Oceanogr 25:840845.[CrossRef]
101. Giovannoni SJ, Rappe M,. 2000. Evolution, diversity, and molecular ecology of marine prokaryotes, pp 4784. In Kirchman DL (ed.), Microbial Ecology of the Oceans. Wiley, New York, NY.
102. Fuhrman J, Hagström Å,. 2008. Bacterial and archaeal community structure and its patterns, pp 4590. In Kirchman D (ed.), Microbial Ecology of the Oceans, 2nd ed. Wiley, Hoboken, New Jersey.
103. Olsen GJ, Lane DL, Giovannoni SJ, Pace NR. 1986. Microbial ecology and evolution: a ribosomal RNA approach. Annu Rev Microbiol 40:337365.[PubMed][CrossRef]
104. Pace NR, Stahl DA, Lane DL, Olsen GJ. 1986. The analysis of natural microbial populations by rRNA sequences. Adv Microb Ecol 9:155.[CrossRef]
105. Venter JC, Remington K, Heidelberg JF, Halpern AL, Rusch D, Eisen JA, Wu DY, Paulsen I, Nelson KE, Nelson W, Fouts DE, Levy S, Knap AH, Lomas MW, Nealson K, White O, Peterson J, Hoffman J, Parsons R, Baden-Tillson H, Pfannkoch C, Rogers YH, Smith HO. 2004. Environmental genome shotgun sequencing of the Sargasso Sea. Science 304:6674.[PubMed][CrossRef]
106. Iverson V, Morris RM, Frazar CD, Berthiaume CT, Morales RL, Armbrust EV. 2012. Untangling genomes from metagenomes: revealing an uncultured class of marine euryarchaeota. Science 335:587590.[PubMed][CrossRef]
107. Sogin ML, Morrison HG, Huber JA, Welch DM, Huse SM, Neal PR, Arrieta JM, Herndl GJ. 2006. Microbial diversity in the deep sea and the underexplored “rare biosphere.” Proc Natl Acad Sci USA 103:1211512120.[PubMed][CrossRef]
108. Lynch MDJ, Neufeld JD. 2015. Ecology and exploration of the rare biosphere. Nat Rev Microbiol 13:217229.[PubMed][CrossRef]
109. Huse S, Welch D, Morrison H, Sogin M. 2010. Ironing out the wrinkles in the rare biosphere through improved OTU clustering. Environ Microbiol 12:18891898.[PubMed][CrossRef]
110. Kunin V, Engelbrektson A, Ochman H, Hugenholtz P. 2010. Wrinkles in the rare biosphere: pyrosequencing errors can lead to artificial inflation of diversity estimates. Environ Microbiol 12:118123.[PubMed][CrossRef]
111. Cuvelier ML, Allen AE, Monier A, McCrow JP, Messié M, Tringe SG, Woyke T, Welsh RM, Ishoey T, Lee J-T, Binder BJ, DuPont CL, Latasa M, Guigand C, Buck KR, Hilton J, Thiagarajan M, Caler E, Read B, Lasken RS, Chavez FP, Worden AZ. 2010. Targeted metagenomics and ecology of globally important uncultured eukaryotic phytoplankton. Proc Natl Acad Sci USA 107:1467914684.[PubMed][CrossRef]
112. Yoon HS, Price DC, Stepanauskas R, Rajah VD, Sieracki ME, Wilson WH, Yang EC, Duffy S, Bhattacharya D. 2011. Single-cell genomics reveals organismal interactions in uncultivated marine protists. Science 332:714717.[PubMed][CrossRef]
113. Rinke C, Schwientek P, Sczyrba A, Ivanova NN, Anderson IJ, Cheng JF, Darling A, Malfatti S, Swan BK, Gies EA, Dodsworth JA, Hedlund BP, Tsiamis G, Sievert SM, Liu WT, Eisen JA, Hallam SJ, Kyrpides NC, Stepanauskas R, Rubin EM, Hugenholtz P, Woyke T. 2013. Insights into the phylogeny and coding potential of microbial dark matter. Nature 499:431437.[PubMed][CrossRef]
114. Stepanauskas R. 2012. Single cell genomics: an individual look at microbes. Curr Opin Microbiol 15:613620.[PubMed][CrossRef]
115. Gifford SM, Sharma S, Booth M, Moran MA. 2013. Expression patterns reveal niche diversification in a marine microbial assemblage. ISME J 7:281298.[PubMed][CrossRef]
116. Gilbert JA, Field D, Huang Y, Edwards R, Li W, Gilna P, Joint I. 2008. Detection of large numbers of novel sequences in the metatranscriptomes of complex marine microbial communities. PLoS One 3:e3042.[PubMed][CrossRef]
117. Hewson I, Poretsky RS, Dyhrman ST, Zielinski B, White AE, Tripp HJ, Montoya JP, Zehr JP. 2009. Microbial community gene expression within colonies of the diazotroph, Trichodesmium, from the Southwest Pacific Ocean. ISME J 3:12861300.[PubMed][CrossRef]
118. Ottesen EA, Young CR, Gifford SM, Eppley JM, Marin R, Schuster SC, Scholin CA, DeLong EF. 2014. Multispecies diel transcriptional oscillations in open ocean heterotrophic bacterial assemblages. Science 345:207212.[PubMed][CrossRef]
119. Shakya M, Quince C, Campbell JHY,Z.K., Schadt CW, Podar M. 2013. Comparative metagenomic and rRNA microbial diversity characterization using archaeal and bacterial synthetic communities. Environ Microbiol 15:18821899.[PubMed][CrossRef]
120. Parada A, Needham DM, Fuhrman JA. 2015. Every base matters: assessing small subunit rRNA primers for marine microbiomes with mock communities, time-series and global field samples. Environ Microbiol 10.1111/1462-2920.13023.[PubMed] http://dx.doi.org/10.1111/1462-2920.13023
121. Giovannoni SJ, Britschgi TB, Moyer CL, Field KG. 1990. Genetic diversity in Sargasso Sea bacterioplankton. Nature 345:6063.[PubMed][CrossRef]
122. Waterbury JB, Watson SW, Guillard RLL, Brand LE. 1979. Widespread occurrence of a unicellular, marine, planktonic cyanobacterium. Nature 227:293294.[CrossRef]
123. Johnson PW, Sieburth JM. 1979. Chroococcoid cyanobacteria in the sea—ubiquitous and diverse phototropic biomass. Limnol Oceanogr 24:928935.[CrossRef]
124. Chisholm SW, Olson RJ, Zettler ER, Waterbury J, Goericke R, Welschmeyer N. 1988. A novel free-living prochlorophyte abundant in the oceanic euphotic zone. Nature 334:340343.[CrossRef]
125. Morris RM, Rappe MS, Connon SA, Vergin KL, Siebold WA, Carlson CA, Giovannoni SJ. 2002. SAR11 clade dominates ocean surface bacterioplankton communities. Nature 420:806810.[PubMed][CrossRef]
126. Fuhrman JA, McCallum K, Davis AA. 1992. Novel major archaebacterial group from marine plankton. Nature 356:148149.[PubMed][CrossRef]
127. Delong EF. 1992. Archaea in coastal marine environments. Proc Natl Acad Sci USA 89:56855689.[PubMed][CrossRef]
128. Karner MB, DeLong EF, Karl DM. 2001. Archaeal dominance in the mesopelagic zone of the Pacific Ocean. Nature 409:507510.[PubMed][CrossRef]
129. Kirchman DL, Elifantz H, Dittel AI, Malmstrom RR, Cottrell MT. 2007. Standing stocks and activity of archaea and bacteria in the western Arctic Ocean. Limnol Oceanogr 52:495507.[CrossRef]
130. Teira E, van Aken H, Veth C, Herndl GJ. 2006. Archaeal uptake of enantiomeric amino acids in the meso- and bathypelagic waters of the North Atlantic. Limnol Oceanogr 51:6069.[CrossRef]
131. Church MJ, DeLong EF, Ducklow HW, Karner MB, Preston CM, Karl DM. 2003. Abundance and distribution of planktonic archaea and bacteria in the waters west of the Antarctic Peninsula. Limnol Oceanogr 48:18931902.[CrossRef]
132. Massana R, DeLong EF, Pedros-Alio C. 2000. A few cosmopolitan phylotypes dominate planktonic archaeal assemblages in widely different oceanic provinces. Appl Environ Microbiol 66:17771787.[PubMed][CrossRef]
133. Garcia-Martinez J, Rodriguez-Valera F. 2000. Microdiversity of uncultured marine prokaryotes: the SAR11 cluster and the marine Archaea of Group I. Mol Ecol 9:935948.[PubMed][CrossRef]
134. Fuhrman J. 2011. Oceans of Crenarchaeota: a personal history describing this paradigm shift. Microbe 6:531537.
135. Brochier-Armanet C, Boussau B, Gribaldo S, Forterre P. 2008. Mesophilic crenarchaeota: proposal for a third archaeal phylum, the Thaumarchaeota. Nature Rev Microbiol 6:245252.[CrossRef]
136. Ouverney CC, Fuhrman JA. 2000. Marine planktonic archaea take up amino acids. Appl Environ Microbiol 66:48294833.[PubMed][CrossRef]
137. Kuypers MMM, Blokker P, Erbacher J, Kinkel H, Pancost RD, Schouten S, Damste JSS. 2001. Massive expansion of marine archaea during a mid-Cretaceous oceanic anoxic event. Science 293:9294.[PubMed][CrossRef]
138. Pearson A, McNichol AP, Benitez-Nelson BC, Hayes JM, Eglinton TI. 2001. Origins of lipid biomarkers in Santa Monica Basin surface sediment: a case study using compound-specific delta C-14 analysis. Geochim Cosmochim Acta 65:31233137.[CrossRef]
139. Wuchter C, Schouten S, Boschker HTS, Damste JSS. 2003. Bicarbonate uptake by marine Crenarchaeota. FEMS Microbiol Lett 219:203207.[PubMed][CrossRef]
140. Schleper C, Jurgens G, Jonuscheit M. 2005. Genomic studies of uncultivated archaea. Nature Rev Microbiol 3:479488.[CrossRef]
141. Konneke M, Bernhard AE, de la Torre JR, Walker CB, Waterbury JB, Stahl DA. 2005. Isolation of an autotrophic ammonia-oxidizing marine archaeon. Nature 437:543546.[PubMed][CrossRef]
142. Martens-Habbena W, Berube PM, Urakawa H, de la Torre JR, Stahl DA. 2009. Ammonia oxidation kinetics determine niche separation of nitrifying archaea and bacteria. Nature 461:976U234.[PubMed][CrossRef]
143. Walker CB, de la Torre JR, Klotz MG, Urakawa H, Pinel N, Arp DJ, Brochier-Armanet C, Chain PSG, Chan PP, Gollabgir A, Hemp J, Hugler M, Karr EA, Konneke M, Shin M, Lawton TJ, Lowe T, Martens-Habbena W, Sayavedra-Soto LA, Lang D, Sievert SM, Rosenzweig AC, Manning G, Stahl DA. 2010. Nitrosopumilus maritimus genome reveals unique mechanisms for nitrification and autotrophy in globally distributed marine crenarchaea. Proc Natl Acad Sci USA 107:88188823.[PubMed][CrossRef]
144. Ingalls AE, Shah SR, Hansman RL, Aluwihare LI, Santos GM, Druffel ERM, Pearson A. 2006. Quantifying archaeal community autotrophy in the mesopelagic ocean using natural radiocarbon. Proc Natl Acad Sci USA 103:64426447.[PubMed][CrossRef]
145. Hansman RL, Griffin S, Watson JT, Druffel ERM, Ingalls AE, Pearson A, Aluwihare LI. 2009. The radiocarbon signature of microorganisms in the mesopelagic ocean. Proc Natl Acad Sci USA 106:65136518.[PubMed][CrossRef]
146. Beja O, Aravind L, Koonin EV, Suzuki MT, Hadd A, Nguyen LP, Jovanovich SB, Gates CM, Feldman RA, Spudich JL, Spudich EN, DeLong EF. 2000. Bacterial rhodopsin: evidence for a new type of phototrophy in the sea [see comments]. Science 289:19021906.[PubMed][CrossRef]
147. Beja O, Spudich EN, Spudich JL, Leclerc M, DeLong EF. 2001. Proteorhodopsin phototrophy in the ocean. Nature 411:786789.[PubMed][CrossRef]
148. Campbell B, Waidner L, Cottrell M, Kirchman D. 2007. Abundant proteorhodopsin genes in the North Atlantic Ocean. Environ Microbiol 10:99109.
149. Frigaard NU, Martinez A, Mincer TJ, DeLong EF. 2006. Proteorhodopsin lateral gene transfer between marine planktonic bacteria and archaea. Nature 439:847850.[PubMed][CrossRef]
150. Fuhrman JA, Schwalbach MS, Stingl U. 2008. Proteorhodopsins: an array of physiological roles? Nature Rev Microbiol 6:488494.
151. Gomez-Consarnau L, Gonzalez JM, Coll-Llado M, Gourdon P, Pascher T, Neutze R, Pedros-Alio C, Pinhassi J. 2007. Light stimulates growth of proteorhodopsin-containing marine Flavobacteria. Nature 445:210213.[PubMed][CrossRef]
152. Gomez-Consarnau L, Akram N, Lindell K, Pedersen A, Neutze R, Milton DL, Gonzalez JM, Pinhassi J. 2010. Proteorhodopsin phototrophy promotes survival of marine bacteria during starvation. PLoS Biol 8:e1000358.[PubMed][CrossRef]
153. Gómez-Consarnau L, González JM, Riedel T, Jaenicke S, Sañudo-Wilhelmy SA, Wagner-Döbler I, Fuhrman JA. 2015. Proteorhodopsin light-enhanced growth linked to vitamin-B1 acquisition in marine Flavobacteria. ISME J 10.1038/ismej.2015.196.[PubMed] http://dx.doi.org/10.1038/ismej.2015.196
154. Shiba T,. 1989. Taxonomy and ecology of marine bacteria, pp 924. In Harashima K, Shiba T, Murata N (eds.), Aerobic Photosynthetic Bacteria. Japan Scientific Societies Press, Tokyo.
155. Yurkov VV, Beatty JT. 1998. Aerobic anoxygenic phototrophic bacteria. Microbiol Mol Biol Rev 62:695724.[PubMed]
156. Kolber ZS, Plumley FG, Lang AS, Beatty JT, Blankenship RE, VanDover CL, Vetriani C, Koblizek M, Rathgeber C, Falkowski PG. 2001. Contribution of aerobic photoheterotrophic bacteria to the carbon cycle in the ocean. Science 292:24922495.[PubMed][CrossRef]
157. Schwalbach MS, Fuhrman JA. 2005. Wide-ranging abundances of aerobic anoxygenic phototrophic bacteria in the world ocean revealed by epifluorescence microscopy and quantitative PCR. Limnol Oceanogr 50:620628.[CrossRef]
158. Goericke R. 2002. Bacteriochlorophyll a in the ocean: is anoxygenic bacterial photosynthesis important? Limnol Oceanogr 47:290295.[CrossRef]
159. Cottrell MT, Mannino A, Kirchman DL. 2006. Aerobic anoxygenic phototrophic bacteria in the Mid-Atlantic Bight and the North Pacific Gyre. Appl Environ Microbiol 72:557564.[PubMed][CrossRef]
160. Lami R, Cottrell MT, Ras J, Ulloa O, Obernosterer I, Claustre H, Kirchman DL, Lebaron P. 2007. High abundances of aerobic anoxygenic photosynthetic bacteria in the South Pacific Ocean. Appl Environ Microbiol 73:41984205.[PubMed][CrossRef]
161. Kirchman DL, Hanson TE. 2013. Bioenergetics of photoheterotrophic bacteria in the oceans. Environ Microbiol 5:188199.[CrossRef]
162. Lopez-Garcia P, Brochier C, Moreira D, Rodriguez-Valera F. 2004. Comparative analysis of a genome fragment of an uncultivated mesopelagic crenarchaeote reveals multiple horizontal gene transfers. Environ Microbiol 6:1934.[PubMed][CrossRef]
163. Fuhrman J. 2003. Genome sequences from the sea. Nature 424:10011002.[PubMed][CrossRef]
164. Palenik B, Brahamsha B, Larimer FW, Land M, Hauser L, Chain P, Lamerdin J, Regala W, Allen EE, McCarren J, Paulsen I, Dufresne A, Partensky F, Webb EA, Waterbury J. 2003. The genome of a motile marine Synechococcus. Nature 424:10371042.[PubMed][CrossRef]
165. Rocap G, Larimer FW, Lamerdin J, Malfatti S, Chain P, Ahlgren NA, Arellano A, Coleman M, Hauser L, Hess WR, Johnson ZI, Land M, Lindell D, Post AF, Regala W, Shah M, Shaw SL, Steglich C, Sullivan MB, Ting CS, Tolonen A, Webb EA, Zinser ER, Chisholm SW. 2003. Genome divergence in two Prochlorococcus ecotypes reflects oceanic niche differentiation. Nature 424:10421047.[PubMed][CrossRef]
166. Kashtan N, Roggensack SE, Rodrigue S, Thompson JW, Biller SJ, Coe A, Ding H, Marttinen P, Malmstrom RR, Stocker R, Follows MJ, Stepanauskas R, Chisholm SW. 2014. Single-cell genomics reveals hundreds of coexisting subpopulations in wild Prochlorococcus. Science 344:416420.[PubMed][CrossRef]
167. Ammerman JW, Fuhrman JA, Hagström Å, Azam F. 1984. Bacterioplankton growth in seawater: I. Growth kinetics and cellular characteristics in seawater cultures. Mar Ecol Prog Ser 18:3139.[CrossRef]
168. Button DK, Schuts F, Quang P, Martin R, Robertson BR. 1993. Viability and isolation of marine bacteria by dilution culture: theory, procedures, and initial results. Appl Environ Microbiol 59:881891.[PubMed]
169. Rappé MS, Connon SA, Vergin KL, Giovannoni SJ. 2002. Cultivation of the ubiquitous SAR11 marine bacterioplankton clade. Nature 418:630633.[PubMed][CrossRef]