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  • Review Article
  • Published:

Tapping into microbial diversity

Key Points

  • Use of molecular techniques in the past 20 years has shown that only an extremely small fraction of the microbial diversity has so far been cultivated from all habitats investigated. How many different microorganisms are out there?

  • Recent research has shown that there is a largely unexplored microbial diversity in extreme environments, such as hot springs, hydrothermal vent sites, in ice and sea ice, in hypersaline environments and environments exhibiting extreme pH.

  • The high-throughput cultivation technologies are capable of producing a large number of cultures that are suitable for supplying adequate diversity for modern high-throughput screening systems in drug discovery.

  • The latest advances in microbial ecology methods, coupled with 16S rRNA phylogeny, could trigger a transformation in microbiology with a focus on new culture-dependent and culture-independent methods to both assess and access microbial diversity.

Abstract

Even though significant advances have been made in understanding microbial diversity, most microorganisms are still only characterized by 'molecular fingerprints' and have resisted cultivation. Many different approaches have been developed to overcome the problems associated with cultivation of microorganisms because one obvious benefit would be the opportunity to investigate the previously inaccessible resources that these microorganisms potentially harbour.

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Figure 1: Reconstructed phylogenetic tree of the domain Bacteria based on 16S rRNA gene sequences.
Figure 2: Flow chart of the recombinant approach for drug discovery.
Figure 3: Flow chart of the high-throughput cultivation process.

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Acknowledgements

We would like to thank M. Rappé (University of Hawaii) for providing the phylogenetic tree, M. l Kulwiec for graphic support, J. M. Short, E. J. Mathur, and G. Woodnut for support. We would like to apologize to our colleagues because, due to space limitations, many references could not be cited.

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Both M. Keller and K. Zengler are employees and shareholders of Diversa Corporation.

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FURTHER INFORMATION

Bacterial nomenclature

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Glossary

ENVIRONMENTAL CLONE LIBRARY

Constructed by cloning environmental DNA samples into suitable vectors.

SUBSURFACE

The environment that is below the Earth's surface and that is independent of any (recent) photosynthetically supplied electron donors or acceptors.

PHYLOTYPE

The evolutionary history of a microbiological species (mostly determined by 16S rRNA gene sequence comparison). Can be compared with a phenotype, which is a physical manifestation of a genetic trait in an organism.

CHEMOLITHOAUTOTROPHIC

Metabolism that uses chemicals as the energy source (chemo) (compared with phototrophic metabolism, which utilizes light as the energy source), inorganic compounds (litho) as electron donors, and carbon dioxide as a carbon source (auto).

LITHOLOGICAL

Pertaining to the character of a rock, as derived from the nature and mode of aggregation of its mineral contents.

HYDROTHERMAL VENT

Areas on the ocean floor where warm or hot fluids are expelled through the Earth's crust to the overlying water. Hydrothermal activity is associated with the spreading centres of the Earth's surface or the subduction of tectonic plates along continental margins. Venting can occur from diffuse low-temperature flows to vigorous venting of hot, reduced fluids that are enriched in metals.

EXTINCTION CULTURES

A given volume of sample is inoculated into culture vessels containing growth media. Successive sets of culture vessels are inoculated by subsequent dilution steps. After an incubation period, the vessels are scored for growth or lack of growth. Those vessels in which growth occurred are assumed to have contained at least one viable microorganism in the inoculant.

MICROCOLONIES

Colonies of 20 to 100 cells that originated from a single bacterial cell. Microcolonies can be formed on solid surfaces or in a microcapsule.

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Keller, M., Zengler, K. Tapping into microbial diversity. Nat Rev Microbiol 2, 141–150 (2004). https://doi.org/10.1038/nrmicro819

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