Microbial metabolic exchange—the chemotype-to-phenotype link

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published online: 15 december 2011 | doi: 10.1038/nchembio.739

microbial metabolic exchange—the chemotypeto-phenotype link

© 2011 Nature America, Inc. All rights reserved.

Vanessa V phelan1,5, Wei-ting liu2,5, Kit pogliano3 & pieter c dorrestein1,2,4*
The function of microbial interactions is to enable microorganisms to survive by establishing a homeostasis betweenmicrobial neighbors and local environments. A microorganism can respond to environmental stimuli using metabolic exchange—the
transfer of molecular factors, including small molecules and proteins. Microbial interactions not only influence the survival of
the microbes but also have roles in morphological and developmental processes of the organisms themselves and their neighbors. This, in turn, shapesthe entire habitat of these organisms. Here we highlight our current understanding of metabolic
exchange as well as the emergence of new technologies that are allowing us to eavesdrop on microbial conversations comprising dozens to hundreds of secreted metabolites that control the behavior, survival and differentiation of members of the
community. The goal of the rapidly advancing field studyingmultifactorial metabolic exchange is to devise a microbial ‘Rosetta
stone’ in order to understand the language by which microbial interactions are negotiated and, ultimately, to control the outcome of these conversations.


icrobial interactions (Fig. 1) exist in nearly every niche on
this planet, ranging from the oral cavity, intestine and skin
of humans, to the cocoons of wasps and downto grains of
sand. When at equilibrium, many microorganisms coexist in stable
mixed communities. When these communities are perturbed, our
ecosystems can be considerably affected, resulting in catastrophic
events that have an impact on our society, such as loss of food sup­
plies, destruction of concrete buildings, deadly animal diseases
and pandemics. Additionally, modern health care,agriculture
and other commercial processes have been shaped by biologically
active metabolites produced by fungi and bacteria1–8. For instance,
the antibiotics penicillin and vancomycin facilitate the control of
microbial infections, the immunosuppressant rapamycin allows
routine organ transplantation and paclitaxel (Taxol) is a critical
treatment for many cancers. Similarly, microbially producedmole­
cules protect our food supplies from microbial and insect invasions;
enhance growth of plants, poultry and cattle; and are also used in
many consumer products, including soap, toothpaste and paints.
Thus, when considering microbially produced metabolites, we often
think in terms of how these metabolites influence our quality of life
but frequently overlook their impact on complexmicrobial inter­
actions and as initiators of multicellular behavior in microbial com­
munities—the purposes for which these metabolites are primarily
produced. For microbes themselves, microbial interactions provide
access to nutrients and protection from external communities and
allow adaptation to changing ecological niches.
Microbes dedicate enormous resources to microbial inter­
actions.The percentages of microbial genomes that are dedicated
to the production of secondary metabolites, a subset of metabolic
exchange factors, have been defined by several studies as approxi­
mately 5–15%. Amazingly, however, the total number of open
reading frames (ORFs) dedicated to microbial interactions has not
been determined despite the importance of microbial interactions
to the survivaland fitness of the individual microbe and the larger
microbial community as a whole9–13. To estimate the proportion
of the bacterial proteome involved in microbial interactions, the

genomes of Staphylococcus aureus subsp. aureus USA300_FPR3757,
Pseudomonas aeruginosa str. PAO1 and Bacillus subtilis subsp.
subtilis str. 168 were obtained from the Pathosystems Resource
Integration Center...
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