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Şimşek^, et al.,
under review at Nature Communications (August 2025)
Keystone engineering enables collective range expansion in microbial communities
In communities harboring multiple species, keystone species are those that impact their community function disproportionately large with respect to their own relative abundance. Those species that impact their communities through altering the shared environment are called keystone engineers.
Here, we show that non-motile, antibiotic-degrading bacteria enables the range expansion of its community under antibiotic treatment if sufficiently close to motile bacteria, whose motility but not growth would otherwise be inhibited by the antibiotic treatment. Effectively, the non-motile bacteria put themselves in a territorial competition with motile bacteria which they lose and, as a result, become extinct or a minority in the community. This is consistent with the notion of keystone engineering, as defined above.
We demonstrated this keystone engineering for a pairwise community of Klebsiella pneumoniae (non-motile) and Pseudomonas aeruginosa (motile) first. Our modeling and experimental analyses revealed that the keystone effect operates at a millimeter scale in this system.
We then demonstrated this keystone engineering by a Bacillus species isolated from a hospital sink, in both pairwise and eight-member bacterial communities with its co-isolates.
Our findings suggest that spatially explicit experiments are essential to understand certain keystone engineering mechanisms and have implications for surface-associated microbial communities like biofilms, as well as for diagnosing and treating polymicrobial infections involving drug-degrading, non-motile (e.g., K. pneumoniae), and drug-tolerant, motile (e.g., P. aeruginosa) bacteria.
Şimşek, et al.,
Molecular Systems Biology (2024)
(also see an insightful commentary by Prof. Kyle R. Allison)
Combining mathematical modeling with quantitative experiments, we investigate spatial population dynamics and resistance evolution of a bacterial community under antibiotic stress with two competing interactions at different length-scales: local collective survival and global resource competition.
We found that
Global resource competition and local “collective survival” lead to heterogeneous growth and development of bacterial colonies (or patchiness).
Under intermediate antibiotic treatment, only a subset of colonies (the “rich”) with a sufficiently large initial seeding density survives.
Surviving colonies benefit from the global pool of resource and grow larger (or get “richer”) than when all colonies survive (in the absence of an antibiotic).
Local collective survival promotes the development of de novo mutants with enhanced antibiotic resistance.
(The wet-lab experiments started with laboratory Escherichia coli with engineered collective survival and then extended to the opportunistic human pathogen Pseudomonas aeruginosa)
Luo*, Lu*, Şimşek*, et al.,
Nature Microbiology (2024)
The collapse of cooperation during range expansion of Pseudomonas aeruginosa
It would not be unfair to say that all organisms cooperate for growth or survival, when needed. But virtually all populations also lend examples of cheaters- those that benefit from the cooperative behavior without contributing to it. Spatial structure is generally assumed to promote the evolutionary stability of cooperation, through clustering the cooperating individuals together so that cheaters cannot take the advantage of them. Oppositely, here we show that spatial structure can also underpin the collapse of cooperation in an expanding microbial population, when the expansion initially mandates cooperation. This cooperation is activated when nutrient levels are not too high but not too low either, at the expense of the cooperating individual's own growth. This expansion in a spatially structured environment allows a prolonged activation of cooperation making it vulnerable to cheating. Furthermore, we demonstrate and characterize divergent evolutionary outcomes of the expansion trait depending on the nutrient levels.
* equal contribution
Bold indicates my first-authorship.
^ corresponding author
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