BACTERIAL PATTERNS

Network analysis of bacterial multi-cellular patterning

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 Obiettivo del progetto (Objective)

'Defining the mechanisms by which cells cooperate to form complex structures and a common function is a fundamental problem in both developmental biology and socio-biology. Cooperative interactions among bacteria are a relatively simple, yet medically important, model system where this problem can be explored in its full generality. Specifically, bacterial growth on surfaces is often accompanied by formation of complex patterns and increased resilience to diverse external insults. The importance of multiple co-existing cellular differentiated states and of specific cell signaling processes, to spatial patterning and development of bacterial communities has been demonstrated in several systems, including the well-characterized microbe, Bacillus subtilis. However, the nature of these interactions and the way they control the spatial organization of differentiation and patterning is unclear. Specifically, we do not understand (1) when and where are genes and cell fates expressed? (2) What is the spatial organization of cell fates? (3) How does the interaction between fates give rise to spatial order? Here, we suggest addressing these questions by utilizing a novel light-activated gene expression system. This will be used to control the spatial and temporal gene expression profile of a library of patterning-related genes. Time-lapse fluorescence microscopy will be used to monitor the dynamic expression of relevant reporters in wild-type and spatially perturbed backgrounds. We will use mathematical modeling to integrate the results into a predictive model of pattern formation and community development. My previous experience in mathematical modeling of spatial systems, and experimental background in developmental genetics, microbiology and advanced microscopy provides a well suited background to successfully pursue this important problem.'

Introduzione (Teaser)

Microbial colonisation in the form of biofilms account for millions of infections annually through contaminated biomedical devices and implants. Better understanding of this process was the subject of a recent study.

Descrizione progetto (Article)

Bacteria often form complex patterns on surfaces called biofilms that increase resilience to diverse external insults such as antimicrobial treatments. While the importance of bacterial communities was previously demonstrated, the control mechanisms of the spatial organisation, differentiation and patterning remain unclear.

The EU-funded project BACTERIAL PATTERNS (Network analysis of bacterial multi-cellular patterning) studied biofilm formation in the model Gram-positive bacteria Bacillus subtilis, which has developmentally different subpopulations. Gene expression studies revealed previously unknown data on biofilm formation in B. subtilis.

Formation of bacterial biofilms is coordinated by means of quorum sensing, a signalling system controlling the population density.

Scientists identified a novel quorum-sensing system called rapP-phrP in biofilm formation. Phosphatase rapP gene exists in a gene cassette with phrP, an encoding regulatory polypeptide. This signalling system was not identified before due to a mutation in the strain used by other researchers. After correcting the mutation, BACTERIAL PATTERNS showed that formation of inter-cellular signalling pathways substantially affects biofilm formation.

A genetic screen approach helped identify multiple novel regulators of biofilm formation, and specifically of surfactin production. Surfactin, produced by B. subtilis, is a powerful surfactant and nonspecific antibiotic, acting on many kinds of bacterial membranes. Identifying the conditions in which the coupling between biofilm formation and sporulation is broken revealed the genetic regulation of this coupling process.

Scientists' uncovered novel data about genetic regulatory mechanisms involved in biofilm formation. Effective anti-bacterial products for domestic, hospital and industrial sectors could be developed by disrupting these mechanisms.