Structure and Physiology of Microbial Biofilms Lab
Our group studies bacterial biofilms of clinical relevance. Biofilms are communities that bacteria form on surfaces by producing an extracellular matrix (ECM) that protects and holds the cells together. Within biofilms, certain subpopulations of bacteria tolerate and survive antibiotic treatments, which seriously compromises the chances of cure of the infections.
Using E. coli as a model microorganism and microbiology, genetics, molecular biology and microscopy techniques, our group aims at understanding how cell subpopulations physiologically differentiate inside biofilms and how this influences the generation of differential spatial patterns of antibiotic tolerance. Understanding these aspects is crucial for the design of treatments that can eliminate all cell subpopulations that coexist within the biofilms. In line with this, our group is also dedicated to discovering novel compounds that can inhibit the formation of E. coli biofilms and to characterize their molecular mechanisms of action.
Due to their structural complexity, biofilms exhibit highly heterogeneous internal microenvironments shaped by gradients of nutrients, metabolic products and signalling compounds. Here, bacterial cells essentially adjust their physiology according to the local conditions, which ultimately causes the stratification of the biofilms into physiologically distinct regions. Our work suggests that this physiological stratification not only represents a division of labor, where cell subpopulations locally specialize in fulfilling specific tasks, such as for example the production of extracellular matrix, but it also endows cell subpopulations with different capacities to cope with stresses as it is the case of antibiotic treatments. Our group is interested in characterizing this physiological stratification in biofilms of commensal and pathogenic E. coli strains and in understanding how this physiological heterogeneity influences the chances of cells to survive antibiotic treatments depending on their location within the biofilm. In particular, we seek to clarify how heterogeneity in the production of extracellular matrix components (amyloid curli and pEtN-cellulose), in stress responses, and in metabolism/growth among cell subpopulations influence antibiotic tolerance in E. coli biofilms. Knowledge of these aspects is crucial to design therapies that can target all cell subpopulations that coexist within these communities, irrespective of their physiological state and spatial location.
Recognizing the need for solutions to combat biofilm-based infections, we are also interested in discovering anti-biofilm compounds and characterizing their molecular mechanisms of action. In particular, we search for compounds that can interfere with the production of amyloid curli and pEtN-cellulose, the major extracellular matrix components, essential for the structural development of E. coli biofilms. As a platform for the search of inhibitors we are exploring microbial interactions in biofilms. While antagonistic interactions among microorganisms have been intensely exploited in the search for antibiotics, i.e., compounds that directly kill or inhibit bacterial growth, these interactions have been overlooked regarding their potential as sources for compounds that, rather than killing the bacteria, modulate or interfere with other bacterial behaviours such as the formation of biofilms. The use of anti-biofilm compounds is crucial in the fight to eradicate biofilm-based infections as they can considerably increase the effectiveness of antibiotics in combined therapies or enhance the efficacy of clearance by the host immune system.
- Bacterial multicellularity: the biology of Escherichia coli building large-scale biofilm communities. Review. Annu. Rev. Microbiol. 75:269-290. Serra D.O. and Hengge R. (2021). doi.org/10.1146/annurev-micro-031921-055801.
- A c-di-GMP-based switch controls local heterogeneity of extracellular matrix synthesis which is crucial for integrity and morphogenesis of Escherichia coli macrocolony biofilms. J Mol Biol. 431(23):4775-4793. Serra D.O. and Hengge R. (2019). doi: 10.1016/j.jmb.2019.04.001
- Spatial organisation of different sigma factor activities and c-di-GMP signalling within the 3D landscape of a bacterial biofilm. Open Biology. 8: 180066. Klauck G., Serra D.O., Possling A. and Hengge R. (2018). doi.org/10.1098/rsob.180066
- Phosphoethanolamine cellulose: a naturally produced chemically modified cellulose. Science. 359, 334-338. Thongsomboon W., Serra D.O., Possling A., Hadjineophytou C., Hengge R. and Cegelski L. (2018). doi: 10.1126/science.aao4096
Article highlighted in:
1) Science|Perspectives Vol. 359, Issue 6373, pp. 276-277. doi: 10.1126/science.aar5253 (http://science.sciencemag.org/content/359/6373/276)
2) Nature|Research highlights (https://www.nature.com/articles/d41586-018-00977-8)
3) Nat Rev Microbiol. (2018);16(3):123. doi: 10.1038/nrmicro.2018.22.
- The green tea polyphenol EGCG inhibits Escherichia coli biofilm formation by impairing amyloid curli fibre assembly and down-regulating the biofilm regulator CsgD via the σE-dependent sRNA RybB. Mol Microbiol. 101(1):136–151. Serra D.O., Mika F., Richter A. and Hengge R. (2016). doi: 10.1111/mmi.13379
Article selected for the cover of issue I (Vol 101, Number 1, Jul 2016) of Mol Microbiol.
- Vertical stratification of matrix production is essential for physical integrity and architecture of macrocolony biofilms of Escherichia coli. Environ Microbiol. 17(12):5073-88. Serra D.O.*, Klauck G.* and Hengge R. (2015). doi: 10.1111/1462-2920.12991
* both authors contributed equally to this work
- Stress responses go 3D – the spatial order of physiological differentiation in bacterial macrocolony biofilms. Environ. Microbiol. 16(6):1455-71. Review. Serra D.O. and Hengge R. (2014). doi: 10.1111/1462-2920.12483.
Article selected for the cover of issue 6 (Vol16) of Environ. Microbiol.
- Cellulose as an architectural element in spatially structured Escherichia coli biofilms. J. Bacteriol. 195(24):5540-54. Serra D.O.*, Richter A.M.* and Hengge R. (2013). doi: 10.1128/JB.00946-13
* both authors contributed equally to this work
Article selected for the cover of issue 24 (Vol 195) of J. Bacteriol.
- Microanatomy at cellular resolution and spatial order of physiological differentiation in a bacterial biofilm. mBio 4(2):e00103-13. doi:10.1128/mBio.00103-13. Serra D.O., Richter A.M., Klauck G., Mika F. and Hengge R. (2013). doi: 10.1128/mBio.00103-13
Article highlighted in Nature Reviews Microbiology (2013) 11, 300–301
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