scholarly journals Synthetic Turing patterns in engineered microbial consortia

2020 ◽  
Author(s):  
Salva Duran-Nebreda ◽  
Jordi Pla ◽  
Blai Vidiella ◽  
Jordi Piñero ◽  
Nuria Conde ◽  
...  

Multicellular entities are characterized by exquisite spatial patterns, intimately related to the functions they perform. Oftentimes these patterns emerge as periodic structures with a well-defined characteristic scale. A candidate mechanism to explain their origins was early introduced by Alan Turing through the interaction and diffusion of two so called morphogens. Unfortunately, most available evidence for Turing patterns in biology is usually obscured by the tangled nature of regulatory phenomena, making difficult to validate Turing’s proposal in developmental processes. Here we follow a different approach, by designing synthetic genetic circuits in engineered E. coli strains that implement the essential activator-inhibitor motif (AIM) using a two-cell consortium. The two diffusible compartments are one cell type (activator, small-diffusion component) and a small signal molecule (a homoserine lactone, acting as the fast-diffusing inhibitor). Using both experimental results, we show that the AIM is capable of generating diffusion-induced instabilities leading to regular spatial patterns. The artificial construction taken here can help validate developmental theories and identify universal properties underpinning biological pattern formation. The implications of the work for the area of synthetic developmental biology are outlined.

2007 ◽  
Vol 73 (20) ◽  
pp. 6339-6344 ◽  
Author(s):  
Tomohiro Morohoshi ◽  
Toshitaka Shiono ◽  
Kiyomi Takidouchi ◽  
Masashi Kato ◽  
Norihiro Kato ◽  
...  

ABSTRACT Quorum sensing is a regulatory system for controlling gene expression in response to increasing cell density. N-Acylhomoserine lactone (AHL) is produced by gram-negative bacteria, which use it as a quorum-sensing signal molecule. Serratia marcescens is a gram-negative opportunistic pathogen which is responsible for an increasing number of serious nosocomial infections. S. marcescens AS-1 produces N-hexanoyl homoserine lactone (C6-HSL) and N-(3-oxohexanoyl) homoserine lactone and regulates prodigiosin production, swarming motility, and biofilm formation by AHL-mediated quorum sensing. We synthesized a series of N-acyl cyclopentylamides with acyl chain lengths ranging from 4 to 12 and estimated their inhibitory effects on prodigiosin production in AS-1. One of these molecules, N-nonanoyl-cyclopentylamide (C9-CPA), had a strong inhibitory effect on prodigiosin production. C9-CPA also inhibited the swarming motility and biofilm formation of AS-1. A competition assay revealed that C9-CPA was able to inhibit quorum sensing at four times the concentration of exogenous C6-HSL and was more effective than the previously reported halogenated furanone. Our results demonstrated that C9-CPA was an effective quorum-sensing inhibitor for S. marcescens AS-1.


Marine Drugs ◽  
2019 ◽  
Vol 17 (9) ◽  
pp. 499 ◽  
Author(s):  
Bao Zhang ◽  
Xiyi Zhuang ◽  
Liyun Guo ◽  
Robert J. C. McLean ◽  
Weihua Chu

Quorum quenching (QQ) is a promising alternative infection-control strategy to antibiotics that controls quorum-regulated virulence without killing the pathogens. Aeromonas hydrophila is an opportunistic gram-negative pathogen living in freshwater and marine environments. A. hydrophila possesses an N-acyl homoserine lactone (AHL)-based quorum-sensing (QS) system that regulates virulence, so quorum signal-inactivation (i.e., QQ) may represent a new way to combat A. hydrophila infection. In this study, an AHL lactonase gene, aiiA was cloned from Bacillus sp. strain QSI-1 and expressed in Escherichia coli strain BL21(DE3). The A. hydrophila hexanoyl homoserine lactone (C6-HSL) QS signal molecule was degraded by AiiAQSI-1, which resulted in a decrease of bacterial swimming motility, reduction of extracellular protease and hemolysin virulence factors, and inhibited the biofilm formation of A. hydrophila YJ-1 in a microtiter assay. In cell culture studies, AiiAQSI-1 decreased the ability of A. hydrophila adherence to and internalization by Epithelioma papulosum cyprini (EPC) cells. During in vivo studies, oral administration of AiiAQSI-1 via feed supplementation attenuated A. hydrophila infection in Crucian Carp. Results from this work indicate that feed supplementation with AiiAQSI-1 protein has potential to control A. hydrophila aquaculture disease via QQ.


Microbiology ◽  
2003 ◽  
Vol 149 (8) ◽  
pp. 1981-1989 ◽  
Author(s):  
Stéphane Uroz ◽  
Cathy D'Angelo-Picard ◽  
Aurélien Carlier ◽  
Miena Elasri ◽  
Carine Sicot ◽  
...  

Bacteria degrading the quorum-sensing (QS) signal molecule N-hexanoylhomoserine lactone were isolated from a tobacco rhizosphere. Twenty-five isolates degrading this homoserine lactone fell into six groups according to their genomic REP-PCR and rrs PCR-RFLP profiles. Representative strains from each group were identified as members of the genera Pseudomonas, Comamonas, Variovorax and Rhodococcus. All these isolates degraded N-acylhomoserine lactones other than the hexanoic acid derivative, albeit with different specificity and kinetics. One of these isolates, Rhodococcus erythropolis strain W2, was used to quench QS-regulated functions of other microbes. In vitro, W2 strongly interfered with violacein production by Chromobacterium violaceum, and transfer of pathogenicity in Agrobacterium tumefaciens. In planta, R. erythropolis W2 markedly reduced the pathogenicity of Pectobacterium carotovorum subsp. carotovorum in potato tubers. These series of results reveal the diversity of the QS-interfering bacteria in the rhizosphere and demonstrate the validity of targeting QS signal molecules to control pathogens with natural bacterial isolates.


2007 ◽  
Vol 73 (7) ◽  
pp. 2329-2332 ◽  
Author(s):  
Maria Stella Medina-Martínez ◽  
Mieke Uyttendaele ◽  
Andreja Rajkovic ◽  
Pol Nadal ◽  
Johan Debevere

ABSTRACT Degradation of the quorum-sensing signal molecule N-acyl-l-homoserine lactone (AHL) in cocultures was verified with Bacillus cereus and Yersinia enterocolitica in culture medium and in pork extract. Results showed evidence of microbial interaction when the AHL-degrading bacterium and AHL-producing bacterium were cocultured in a food-simulating condition.


2004 ◽  
Vol 48 (9) ◽  
pp. 3457-3461 ◽  
Author(s):  
Yoshifumi Imamura ◽  
Katsunori Yanagihara ◽  
Yohei Mizuta ◽  
Masafumi Seki ◽  
Hideaki Ohno ◽  
...  

ABSTRACT The features of chronic airway diseases, including chronic bronchitis, cystic fibrosis, bronchiectasis, and diffuse panbronchiolitis, include chronic bacterial infection and airway obstruction by mucus. Pseudomonas aeruginosa is one of the most common pathogens in chronic lung infection, and quorum-sensing systems contribute to the pathogenesis of this disease. The quorum-sensing signal molecule [N-(3-oxododecanoyl) homoserine lactone (3O-C12-HSL)] not only regulates bacterial virulence but also is associated with the immune response. In this study, we investigated whether 3O-C12-HSL could stimulate the production of a major mucin core protein, MUC5AC. The effect of a macrolide on MUC5AC production was also studied. 3O-C12-HSL induced NCI-H292 cells to express MUC5AC at both the mRNA and the protein levels in time- and dose-dependent manners. A 15-membered macrolide, azithromycin, inhibited MUC5AC production that was activated by 3O-C12-HSL. 3O-C12-HSL induced extracellular signal-regulated kinase (ERK) 1/2 and I-κB phosphorylation in cells, and this induction was suppressed by azithromycin. 3O-C12-HSL-induced MUC5AC production was blocked by the ERK pathway inhibitor PD98059. Our findings suggest that the P. aeruginosa autoinducer 3O-C12-HSL contributes to excessive mucin production in chronic bacterial infection. Azithromycin seems to reduce this mucin production by interfering with intracellular signal transduction.


2013 ◽  
Vol 76 (8) ◽  
pp. 1350-1358 ◽  
Author(s):  
DONG HWAN LEE ◽  
JIN-BEOM KIM ◽  
MIHYUN KIM ◽  
EUNJUNG ROH ◽  
KYUSUK JUNG ◽  
...  

Spoilage causes vegetables to deteriorate and develop unpleasant characteristics. Approximately 30% of fresh vegetables are lost to spoilage, mainly due to colonization by bacteria. In the present study, a total of 44 bacterial isolates were obtained from a number of spoiled vegetables. The isolates were identified and classified into 20 different species of 14 genera based on fatty acid composition, biochemical tests, and 16S rDNA sequence analyses. Pseudomonas spp. were the species most frequently isolated from the spoiled vegetables. To evaluate the spoilage ability of each species, a variety of fresh vegetables were treated with each isolate and their degree of maceration was observed. In addition, the production of plant cell wall-degrading enzymes (PCWDEs), such as cellulase, xylanase, pectate lyase, and polygalacturonase, was compared among isolates to investigate their potential associations with spoilage. Strains that produce more PCWDEs cause spoilage on more diverse plants, and pectinase may be the most important enzyme among PCWDEs for vegetable spoilage. Most gram-negative spoilage bacteria produced acylated homoserine lactone, a quorum-sensing signal molecule, suggesting that it may be possible to use this compound effectively to prevent or slow down the spoilage of vegetables contaminated with diverse bacteria.


2007 ◽  
Vol 189 (22) ◽  
pp. 8333-8338 ◽  
Author(s):  
Tomohiro Morohoshi ◽  
Yuta Nakamura ◽  
Go Yamazaki ◽  
Akio Ishida ◽  
Norihiro Kato ◽  
...  

ABSTRACT A number of gram-negative bacteria have a quorum-sensing system and produce N-acyl-l-homoserine lactone (AHL) that they use them as a quorum-sensing signal molecule. Pantoea ananatis is reported as a common colonist of wheat heads at ripening and causes center rot of onion. In this study, we demonstrated that P. ananatis SK-1 produced two AHLs, N-hexanoyl-l-homoserine lactone (C6-HSL) and N-(3-oxohexanoyl)-l-homoserine lactone (3-oxo-C6-HSL). We cloned the AHL-synthase gene (eanI) and AHL-receptor gene (eanR) and revealed that the deduced amino acid sequence of EanI/EanR showed high identity to those of EsaI/EsaR from P. stewartii. EanR repressed the ean box sequence and the addition of AHLs resulted in derepression of ean box. Inactivation of the chromosomal eanI gene in SK-1 caused disruption of exopolysaccharide (EPS) biosynthesis, biofilm formation, and infection of onion leaves, which were recovered by adding exogenous 3-oxo-C6-HSL. These results demonstrated that the quorum-sensing system involved the biosynthesis of EPS, biofilm formation, and infection of onion leaves in P. ananatis SK-1.


2021 ◽  
Author(s):  
Sankalpa Venkatraghavan ◽  
Sathvik Anantakrishnan ◽  
Karthik Raman

AbstractMicrobial consortia exhibit spatial patterning in several environments. However, the study of such patterning is limited by the inherent complexity of natural systems. An attractive alternative to study such systems involves the use of model synthetic microbial communities, which are convenient frameworks that allow the reuse of circuit components by eliminating cross-talk through compartmentalization of modules in genetic circuits. Computational models facilitate the understanding of how spatial organization can be harnessed as a tunable parameter in 2D cultures. We propose a Quorum Sensing-Mediated Model to engineer communication between strains in a consortium. This is implemented using a cellular automaton. We further analyze the properties of this model and compare them with those of the traditionally used Metabolite Mediated Model. Our studies indicate that modulating the rate of secretion of quorum sensing molecules is the most effective means of regulating community behavior. The models and codes are available from https://github.com/RamanLab/picCASO.


Author(s):  
Irving R. Epstein ◽  
John A. Pojman

In the first chapter of this book, we noted the “dark age” of nearly forty years separating the work of Bray and Lotka in the early 1920s and the discovery of the BZ reaction in the late 1950s. Remarkably, the history of nonlinear chemical dynamics contains another gap of almost the same length. In 1952, the British mathematician Alan Turing wrote a paper in which he suggested that chemical reactions with appropriate nonlinear kinetics coupled to diffusion could lead to the formation of stationary patterns of the type encountered in living organisms. It took until 1990 for the first conclusive experimental evidence of Turing patterns to appear (Castets et al., 1990). Turing was a formidable figure (Hodges, 1983). He was responsible for much of the fundamental work that underlies the formal theory of computation, and the notion of a “Turing machine” is essential for anyone who wishes to understand computing and computers. During World War II, Turing was a key figure in the successful effort to break the Axis “Enigma” code, an accomplishment that almost certainly saved many lives and shortened the war in Europe. His 1952 paper, entitled “The Chemical Basis of Morphogenesis” was his only published venture into chemistry, but its impact has been enormous. Recently, this classic paper has been reprinted along with some of Turing's unpublished notes on the origins of phyllotaxis, the arrangement of leaves on the stems of plants (Saunders, 1992). In this chapter, we shall describe the nature of Turing patterns and some of the systems in which they may play a role, explore why they have been so elusive, examine the experimental systems in which they have been demonstrated, and consider other systems and other methods for generating them. Much of our discussion will focus on the chlorite-iodide-malonic acid (CIMA) reaction in which the patterns were first seen. In the study of Turing patterns, the CIMA system and its relatives play much the same role today that the BZ reaction played during the 1960s and 1970s in the study of chemical oscillation.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Hongwei Yin ◽  
Xiaoyong Xiao ◽  
Xiaoqing Wen

For a predator-prey system, cross-diffusion has been confirmed to emerge Turing patterns. However, in the real world, the tendency for prey and predators moving along the direction of lower density of their own species, called self-diffusion, should be considered. For this, we investigate Turing instability for a predator-prey system with nonlinear diffusion terms including the normal diffusion, cross-diffusion, and self-diffusion. A sufficient condition of Turing instability for this system is obtained by analyzing the linear stability of spatial homogeneous equilibrium state of this model. A series of numerical simulations reveal Turing parameter regions of the interaction of diffusion parameters. According to these regions, we further demonstrate dispersion relations and spatial patterns. Our results indicate that self-diffusion plays an important role in the spatial patterns.


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