Single-cell variability of growth interactions within a two-species bacterial community

Abstract

Cell-cell interaction networks have been examined in many high diversity microbial communities using macroscale approaches. Microscale studies of multispecies communities are lacking and it remains unclear how macroscale trends scale down to small groups of cells. Experimental approaches using microfluidic devices have revealed heterogeneity in the behavior of single cells, however, this analysis has not been extended towards the variability of cell-cell interactions. Using a microwell device, we analyzed cell growth within hundreds of replicate microbial communities consisting of two species and small population sizes. The wells of the devices were inoculated with a coculture of Escherichia coli and Enterobacter cloacae. Each species expressed a unique fluorescent protein enabling simultaneously tracking of cell number for each species over time. Growth dynamics within the device were consistent with bulk measurements. The device enabled monitoring of replicate, isolated coculture populations at high magnification, revealing both the growth interaction between the two species and the variability of such cell-cell interactions within small groups of cells. The device enables new experimental measurements of the heterogeneity of interactions within small, multispecies populations of bacteria.

Microfluidic and mathematical modeling of aquatic microbial communities

“…Although they have not yet been employed for investigating algal-associated communities, the capability of microchambers for co-culture has been demonstrated in other microbial communities. For example, Guo et al studied single-cell variability in an array of microwells using a co-culture system of Escherichia coli and Enterobacter cloacae [27]. The microfluidic platform enabled them to investigate the heterogeneity of cell growth rate at the single-cell level.…”

Computation in bacterial communities

“…Are there important consequences for populations when two rare phenotypes of different species interact? One recent experiment to report on this concept [90], examined the coupling of growth rates within small, mixed populations of E. coli and Enterobacter cloacae. Using a microwell device to create replicate groups containing only a few cells of each species, it was found that the mean and variability of growth rates was higher in co-cultures than single strain cultures.…”

Cell size regulation and proliferation fluctuations in single-cell derived colonies

“…Most cellular properties are subject to random variability (noise) [1]- [3]. Although these fluctuations are traditionally studied in single-cell variables, such as protein levels, stochasticity also affects collective variables involving cell populations such as gene drift [4], [5], host invasion by pathogen cells [6], the survival of small groups to antimicrobial treatment [7], ecology of cell populations [8], size-based interactions [9] and metabolite production [10].…”