Projects / Programmes
Investigations of bacterial social interactions in biotechnologically and medically important microbial biofilms
| Code |
Science |
Field |
Subfield |
| 4.06.04 |
Biotechnical sciences |
Biotechnology |
Microbe biotechnology |
| Code |
Science |
Field |
| T490 |
Technological sciences |
Biotechnology |
| Code |
Science |
Field |
| 3.04 |
Medical and Health Sciences |
Medical biotechnology |
microbial biotechnology, bacterial social inetractions, mixed biofilms, antibiotics, polymers, viscoelastic properties.
Researchers (20)
Organisations (2)
Abstract
1. Scientific background: Bacteria have evolved over billions of years to engage in multicellular networks dominated by complex social interactions. Although bacteria have ability to live independent solitary lifestyle they continuously adapt to the presence of other microorganisms. In fact, it is believed that 17 – 42 % of predicted ORFs in published genomes are dedicated to microbial interactions (Phelan et al., 2012), which are mediated by secreted molecules (public goods) such as signals, surfactants, antibiotics, toxins, extracellular polymers, extracellular enzymes. These influence the fitness and physiology of the producer as well as of neighbouring bacteria (Oslizlo et al., 2014). Social interactions are especially intense in biofilms where cells live in close proximity and are glued together by complex network of extracellular polymers (Dogša et al., 2014). For example, Bacillus and Actinomyces species, both soil dwelling and industrially important Gram-positive bacteria, may mutually influence the production of each other’s public goods in biofilms (Traxler and Kolter, 2015). Actinomycetes are known antibiotic producers and the genome of Streptomyces rapamycinicus has around 45 potential secondary metabolite gene clusters but only three compounds have been identified to date (Baranasic et al., 2013). An important unanswered question is if Bacillus subtilis, a producer of a variety of secondary metabolites (antibiotics, surfactants), influence the production of secondary metabolites in Streptomyces. Bacillus species are ubiquitous in the environment and may form biofilms on many different surfaces including human/animal gut. In this environment it is likely that it comes into contact with C. jejuni, one of the leading causes of human gastroenteritis worldwide (Smole Možina et al., 2011), providing a platform for C. jejuni biofilm formation that will also be studied in the project.
2. Problem identification: Bacteria are traditionally studied as monocultures, although in the environment they mainly exist in mixed biofilms. As social interactions in mixed biofilms affect expression of public goods (signals, surfactants, antibiotics, toxins and extracellular enzymes) a substantially better understanding of social interaction mechanisms is need for new applications in medicine, biotechnology and industrial microbiology.
3. Project aims and their potential impact: The project aims to investigate basic mechanisms of intra and interspecies social interactions that affect development of mixed biofilms, fitness of interacting bacteria, synthesis of antibiotics and matrix polymers, stress response, and mechanical properties of biofilms. State of the art will be used to explore three model bacteria (Bacillus, Streptomyces, Campylobacter) grown as monocultures and as mixed biofilms or planktonic cocultures. The research proposed brings together experts from Slovenia (BF and Acies Bio) and renowned researchers from abroad (Harvard University, Oxford University, Copenhagen University, Aberdeen University, Helmholtz Institute, and Iowa University). It is expected that the proposed project will identify new ways of boosting silent antibiotic synthesis. Studying factors that promote pathogen biofilm formation may provide new avenues to treat or prevent disease and pathogen transmission. The results will supply valuable data on how microbial population associate in social groups and form cooperative microbial societies or engage in microbial warfare.
Significance for science
The proposed project is based on the new paradigm of the highly structured and complex microbial networks that are dependent on microbial social interactions. Social microbiology is an emerging and dynamic field of research that is changing our perceptions of the microbial world and we believe that the results of this project will further boost our understanding of microbial social interactions. The project is tightly linked to the priorities of Horizon 2020 and important for development of science in Slovenia. In the proposed project we will explore the mechanical properties of mixed species biofilms and distribution of cell clusters in these multicellular structures, which is a new and innovative approach to study microbial social interactions. In addition, research proposed will uncover how intra and interspecies interactions influence the synthesis of extracellular signaling molecules, extracellular components of biofilm matrix, antibiotics and the role of stress response in microbial competition. By including the genome wide transcriptional responses of mixed species biofilms and cocultures we will obtain a holistic view on plasticity of interacting bacteria. In addition a fluorescence/confocal microscopy will enable us to obtain a 3D understanding of microbial interactions, distribution of cells in biofilms and their activities at the single cell level. This will allow us to get new knowledge on the most frequent foodborne enteropathogen in Slovenia and EU, Campylobacter jejuni and the two industrially important microorganisms: Bacillus in Streptomyces. One of the project goals aims at a discovery of novel antibiotics, through activation of silent gene clusters. The recent American patent for the discovery of a novel antibiotic that we have obtained proves that only through a thorough understanding of basic microbiology, as proposed in this project, one hopes to obtain new high-tech products. The project will enhance collaboration within the group as well as with researchers from abroad at Universities of
Harvard, Oxford, Groningen, Copenhagen Iowa, and Helmholtz Institute. We believe that the results of the project will provide an exciting environment to attract good students.
Significance for the country
Given the large medical and industrial significance of natural products, whose total market currently exceeds 50 billion USD, it is not surprising that a lot of effort has been invested in the past in the study of their biosynthesis. Especially in the field of anti-infectives and anti cancer therapy there is still a great need to develop more effective therapies and a growing number of natural products are currently in clinical trials. Analysis of numerous microbial genomes in recent years has shown that a large number of micro-organisms contain “silent” gene clusters for the biosynthesis of secondary metabolites, which are not expressed and their enormous potential for pharmaceutical use remains untapped. Although we are proposing a basic scientific project whose main objectives are new scientific discoveries addressing social interactions between bacteria, the knowledge obtained will provide a solid base for future application-oriented research. The industrial partner in the project, Acies Bio, has in the past identified several interesting natural compounds protected by patent, and currently develops these compounds as anti-bacterials active against multi-resistant pathogens. It is hoped that "silent" gene clusters activation that will be studied in this project may provide the basis for the future protection of intellectual property rights and further application development. New findings on interactions between Campylobacter with Bacillus subtilis may have the potential for the control of this pathogen in conjunction with the probiotic B. subtilis species. The latter is not only industrially interesting, as a producer of many important enzymes, antibiotics and polymers, but is also used as to degrade pollutants and as plant growth promoting bacterium, biopesticide and probiotic. The untapped potential of these bacteria is the production of extracellular polymers, which are increasingly sought by the pharmaceutical and food industries, will be studied as one of the topics of this research project. Social interactions between microbes addressed in this project are therefore of great importance also from a society perspective. Bio-economy in the EU represents approx. 2,000 billion euros and employs about 22 million people and represents one of the most important parts of the economy in the EU. It is expected that the results of the project will contribute to increasing innovation capacity and competitiveness of the Slovenian bioeconomy. The project is also fully aligned with the proposed Slovenian strategy of smart specialization, priority (S) INDUSTRY 4.0 - Medicine.
Most important scientific results
Interim report,
final report
Most important socioeconomically and culturally relevant results
Interim report,
final report
