Probing patterning in microbial consortia with a cellular automaton for spatial organisation

Abstract

Microbial consortia exhibit spatial patterning across diverse environments. Since probing the self-organization of natural microbial communities is limited by their inherent complexity, synthetic models have emerged as attractive alternatives. In this study, we develop novel frameworks of bacterial communication and explore the emergent spatiotemporal organization of microbes. Specifically, we built quorum sensing-mediated models of microbial growth that are utilized to characterize the dynamics of communities from arbitrary initial configurations and establish the effectiveness of our communication strategies in coupling the growth rates of microbes. Our simulations indicate that the behavior of quorum sensing-coupled consortia can be most effectively modulated by the rates of secretion of acyl homoserine lactones. Such a mechanism of control enables the construction of desired relative populations of constituent species in spatially organized populations. Our models accurately recapitulate previous experiments that have investigated pattern formation in synthetic multi-cellular systems. Additionally, our software tool enables the easy implementation and analysis of our frameworks for a variety of initial configurations and simplifies the development of sophisticated gene circuits facilitating distributed computing. Overall, we demonstrate the potential of spatial organization as a tunable parameter in synthetic biology by introducing a communication paradigm based on the location and strength of coupling of microbial strains.

Identifying LasR Quorum Sensors with Improved Signal Specificity by Mapping the Sequence–Function Landscape

“…In this study, we aimed to assess the protein sequence–function relationship for ligand specificity of LasR and to understand how problematic signal crosstalk for this biosensor could be mitigated. LasR is among a subset of well-studied LuxR-type quorum sensors that have been commonly used in combination to elicit multicellular bacterial responses. ,,,− The LasR symmetrical homodimer binds reversibly to its cognate ligand 3-oxo-C12-HSL (C12-HSL). However, ligand promiscuity and spurious activation of LasR by other long-acyl chain HSLs are well-known and are especially prominent for 3-hydroxy-C14-HSL (C14-HSL), the cognate signal of the LuxR-type regulator CinR from Rhizobium etli ,, (Supplementary Figure S1).…”

On the origin of the extinction of the (human) species

“…Besides basic instincts, all living beings seem to also share the same biological functions, which grounds one of the most relevant Darwin´s assumptions -biological functions differ in form but not in kind across species (Darwin, 1859). This assumption has been gaining increasing evidence for several biological functions, including those linked with nervous circuits (Kraigher et al, 2022;Monaco et al, 2022;Natan et al, 2019;Timsit, & Grégoire, 2021;Venkatraghavan et al, 2022;Wang et al, 2020). In fact, science has been suggesting that even though cells and unicellular microorganisms do not have nervous systems per se, they have "molecular brains" (cf.…”

“…In turn, there are also several examples in nature of successful collaborative efforts between uni-and multicellular species, such as microbial consortia (i.e., a group of diverse microorganisms that occupy a favorable environment and exchange numerous advantages to their shared host; see Venkatraghavan et al, 2022 for an overview on this topic), or between non-kin and kin multicellular species (e.g., Clutton-Brock, 2009).…”

“…Moreover, a coordinated communication within and between cells and organisms also played (and still plays) a key evolutionary role in both uni-and multicellular organisms from inter/intraspecies, allowing the synchronization and adaptation of organisms to the ancestral constraints and ecological conditions of the changing environment (Combarnous, & Nguyen, 2020;Del Sol et al, 2019;Lynn & Leenheer, 2019;Pearce et al, 2018;Staps et al, 2019;Stokar-Avihail et al, 2019;Takagi et al, 2020). Both in and between uni-and multicellular organisms, these collaborative efforts were selected during evolution mostly when it led to a mutually beneficial equilibrium for two (or more) communicating species (Combarnous, & Nguyen, 2020;Pearce et al, 2018;Staps et al, 2019;Takagi et al, 2020;Venkatraghavan et al, 2022;Wang et al, 2020). Thus, intra/interspecies cooperation is recognized as an important evolutionary strength, which appears to be invariant across time, species, and space, with its onset being ascribed at least to the first forms of life, 3,8 billion years ago (Combarnous, & Nguyen, 2020;Hilbe et al, 2018;Pearce et al, 2018;Staps et al, 2019;Takagi et al, 2020;Venkatraghavan et al, 2022;Wang et al, 2020).…”

“…Both in and between uni-and multicellular organisms, these collaborative efforts were selected during evolution mostly when it led to a mutually beneficial equilibrium for two (or more) communicating species (Combarnous, & Nguyen, 2020;Pearce et al, 2018;Staps et al, 2019;Takagi et al, 2020;Venkatraghavan et al, 2022;Wang et al, 2020). Thus, intra/interspecies cooperation is recognized as an important evolutionary strength, which appears to be invariant across time, species, and space, with its onset being ascribed at least to the first forms of life, 3,8 billion years ago (Combarnous, & Nguyen, 2020;Hilbe et al, 2018;Pearce et al, 2018;Staps et al, 2019;Takagi et al, 2020;Venkatraghavan et al, 2022;Wang et al, 2020). However, intra/inter species competition seems to also play a crucial role in the evolutionary story of life (Abreu et al, 2019;Celiker & Gore, 2012;Clutton-Brock, 2009;Govaert et al, 2018;Griffins et al, 2004;Hogle et al, 2023;Monaco et al, 2022;Nair et al, 2019;Wang et al, 2020;Yamamichi et al, 2022).…”