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Metabolic co-dependence gives rise to collective oscillations within biofilms.

Liu J, Prindle A, Humphries J, Gabalda-Sagarra M, Asally M, Lee DY, Ly S, Garcia-Ojalvo J, Süel GM - Nature (2015)

Bottom Line: It remains unclear how these opposing interactions are resolved at the population level.We discover that this conflict between protection and starvation is resolved through emergence of long-range metabolic co-dependence between peripheral and interior cells.As a result, biofilm growth halts periodically, increasing nutrient availability for the sheltered interior cells.

View Article: PubMed Central - PubMed

Affiliation: Division of Biological Sciences, University of California San Diego, California 92093, USA.

ABSTRACT
Cells that reside within a community can cooperate and also compete with each other for resources. It remains unclear how these opposing interactions are resolved at the population level. Here we investigate such an internal conflict within a microbial (Bacillus subtilis) biofilm community: cells in the biofilm periphery not only protect interior cells from external attack but also starve them through nutrient consumption. We discover that this conflict between protection and starvation is resolved through emergence of long-range metabolic co-dependence between peripheral and interior cells. As a result, biofilm growth halts periodically, increasing nutrient availability for the sheltered interior cells. We show that this collective oscillation in biofilm growth benefits the community in the event of a chemical attack. These findings indicate that oscillations support population-level conflict resolution by coordinating competing metabolic demands in space and time, suggesting new strategies to control biofilm growth.

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Effects of external ammonium on biofilm development. a, Addition of external ammonium (red shading, 1 mM) represses expression from the PnasA-YFP reporter (black), but does not affect expression from a constitutive reporter (Phyperspank-CFP + 1 mM IPTG, gray). b, Removal of external ammonium (red shading, 13 mM) causes halting of colony growth.
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Figure 9: Effects of external ammonium on biofilm development. a, Addition of external ammonium (red shading, 1 mM) represses expression from the PnasA-YFP reporter (black), but does not affect expression from a constitutive reporter (Phyperspank-CFP + 1 mM IPTG, gray). b, Removal of external ammonium (red shading, 13 mM) causes halting of colony growth.

Mentions: Since cells can self-produce ammonium from glutamate, we next sought to determine how peripheral cells could experience periodic ammonium limitation despite a constant supply of glutamate in the media. It is well known that ammonium production is a highly regulated process that is dependent on the metabolic state of the cell and the ambient level of ammonium in the environment22. In particular, since ammonium is in equilibrium with ammonia vapor, which can freely cross the cell membrane and be lost to the extracellular media23, the production of ammonium is known as a “futile cycle”. Cells therefore preferentially use extracellular (ambient) ammonium for growth, rather than producing their own24–26. Since peripheral cells are exposed to media flow, they are particularly susceptible to this futile cycle of ammonia loss. In this sense, since ammonium is not provided in the media, even if all cells produce ammonium, the biofilm interior will be the major source for ambient ammonium (Fig. 2d). Consequently, the simplifying hypothesis is that growth of peripheral cells relies on ammonium produced within the biofilm. To test this conjecture, we supplemented the media with 1 mM ammonium, which eliminated the periodic halting in biofilm expansion (Fig. 2g and Extended Data Fig.3b and 5a). When additional ammonium was suddenly removed from the media, growth in the biofilm periphery halted as expected (Extended Data Fig. 5b). These findings indicate that peripheral cells preferentially rely on extracellular ammonium produced within the biofilm for their growth.


Metabolic co-dependence gives rise to collective oscillations within biofilms.

Liu J, Prindle A, Humphries J, Gabalda-Sagarra M, Asally M, Lee DY, Ly S, Garcia-Ojalvo J, Süel GM - Nature (2015)

Effects of external ammonium on biofilm development. a, Addition of external ammonium (red shading, 1 mM) represses expression from the PnasA-YFP reporter (black), but does not affect expression from a constitutive reporter (Phyperspank-CFP + 1 mM IPTG, gray). b, Removal of external ammonium (red shading, 13 mM) causes halting of colony growth.
© Copyright Policy - permissions-link
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4862617&req=5

Figure 9: Effects of external ammonium on biofilm development. a, Addition of external ammonium (red shading, 1 mM) represses expression from the PnasA-YFP reporter (black), but does not affect expression from a constitutive reporter (Phyperspank-CFP + 1 mM IPTG, gray). b, Removal of external ammonium (red shading, 13 mM) causes halting of colony growth.
Mentions: Since cells can self-produce ammonium from glutamate, we next sought to determine how peripheral cells could experience periodic ammonium limitation despite a constant supply of glutamate in the media. It is well known that ammonium production is a highly regulated process that is dependent on the metabolic state of the cell and the ambient level of ammonium in the environment22. In particular, since ammonium is in equilibrium with ammonia vapor, which can freely cross the cell membrane and be lost to the extracellular media23, the production of ammonium is known as a “futile cycle”. Cells therefore preferentially use extracellular (ambient) ammonium for growth, rather than producing their own24–26. Since peripheral cells are exposed to media flow, they are particularly susceptible to this futile cycle of ammonia loss. In this sense, since ammonium is not provided in the media, even if all cells produce ammonium, the biofilm interior will be the major source for ambient ammonium (Fig. 2d). Consequently, the simplifying hypothesis is that growth of peripheral cells relies on ammonium produced within the biofilm. To test this conjecture, we supplemented the media with 1 mM ammonium, which eliminated the periodic halting in biofilm expansion (Fig. 2g and Extended Data Fig.3b and 5a). When additional ammonium was suddenly removed from the media, growth in the biofilm periphery halted as expected (Extended Data Fig. 5b). These findings indicate that peripheral cells preferentially rely on extracellular ammonium produced within the biofilm for their growth.

Bottom Line: It remains unclear how these opposing interactions are resolved at the population level.We discover that this conflict between protection and starvation is resolved through emergence of long-range metabolic co-dependence between peripheral and interior cells.As a result, biofilm growth halts periodically, increasing nutrient availability for the sheltered interior cells.

View Article: PubMed Central - PubMed

Affiliation: Division of Biological Sciences, University of California San Diego, California 92093, USA.

ABSTRACT
Cells that reside within a community can cooperate and also compete with each other for resources. It remains unclear how these opposing interactions are resolved at the population level. Here we investigate such an internal conflict within a microbial (Bacillus subtilis) biofilm community: cells in the biofilm periphery not only protect interior cells from external attack but also starve them through nutrient consumption. We discover that this conflict between protection and starvation is resolved through emergence of long-range metabolic co-dependence between peripheral and interior cells. As a result, biofilm growth halts periodically, increasing nutrient availability for the sheltered interior cells. We show that this collective oscillation in biofilm growth benefits the community in the event of a chemical attack. These findings indicate that oscillations support population-level conflict resolution by coordinating competing metabolic demands in space and time, suggesting new strategies to control biofilm growth.

Show MeSH
Related in: MedlinePlus