The work published in the prestigious journal Current Biology, IF=8.9, for the first time describes the molecular mechanisms behind a fascinating ability of bacteria to discriminate between and respond differentially to kin and non-kin; phenomenon identified as bacterial kin discrimination. By using transposon mutagenesis, reverse genetics, transcriptomics, comparative genomics and swarming compatibility assay we showed for the first time in collaboration with Harvard that KD relays on combinatorial system involving several genetic loci. These function in 1) attack and defense, 2) synthesis of bacterial cell wall, 3) production of the major extracellular polysaccharide Eps and as 4) regulatory factors involved in stress response. The number of different attack and defense functions increases with phylogenetic distance between strains. The KD in B. subtilis is of combinatorial nature as it relies on more than one genetic determinant which are present in natural strains in different combinations and provide a dynamic system for assortment of strains based on their relatedness which are expected to have overlapping ecological niches. This KD system may therefore stabilize cooperation between kin. The paper has been already cited 6 times.
In the book entitled ˝How to overcome the antibiotic crisis: facts, challenges, technologies and future perspectives” (Springer), in collaboration with researchers from Helmholtz Centre for Infection Research (HZI), that are collaborators within this project, we have described a new approaches dedicated to the development of new lead structures against infectious diseases and, in particular, new antibiotics against hard-to-treat and multidrug-resistant bacterial pathogens. New approaches are described in connection with three new antibiotics currently under development at HZI. One of these three new antibiotics currently under preclinical development, relating to atypical tetracycline analogue is being developed in collaboration between researchers from Biotechnical faculty and Acies Bio d.o.o. (members of the project team) in collaboration to HZI, which is described in the book chapter.
In this work, which involves the development of methodology required for the execution of this project, we report on the structure and dynamics of biologically important model polymer mixtures that mimic the extracellular polymeric matrix in native biofilm of Bacillus subtilis. This biofilm is rich in nonionic polysaccharide levan, but also contains other biopolymers such as eDNA and proteins in small concentrations. By applying the dynamic rheology, small-angle X-ray scattering, dynamic light scattering, microscopy, densitometry, and sound velocity measurements we were able to conclude that the addition of eDNA to levan solution increased the viscosity, pseudoplasticity, and elasticity of the system. The addition of protein increased the rigidity of the system. The role of levan was merely a filling agent. The mechanical properties of model mixtures compared well with the mechanical properties of native biofilms.