The role of extracellular DNA in the maintenance of biofilms formed by gram-positive and gram-negative bacteria was studied. This study evaluated all the bacterial strains that were tested for the presence of extracellular DNA with an average size of 30 kb in the matrix. Our results indicate changes in community biomass, architecture, morphology, and the numbers of CFU in the presence of DNase. This effect seems to be common to biofilms established by various unrelated gram-positive and gram-negative bacteria. The cleavage of extracellular DNA leads to the formation of an altered biofilm that permits the increased penetration of antibiotics. Thus, the addition of DNase enhances the effect of antibiotics, resulting in decreased biofilm biomass and numbers of CFU.It is well known that bacteria form biofilms, in which they survive in the presence of high concentrations of antimicrobial agents (13,23,28,51,52,55). Antibiotics at concentrations of 10 2 to 10 4 times the MIC cause no killing effect on the bacteria in biofilm communities (2,7,14,22,24,32,54). Bacterial survival in biofilms may be determined by multiple different factors. Biofilms are covered by a surface film composed of lipid components similar to those in bacterial membranes, which are a barrier for the penetration of some antibiotics (57, 59). The roles of separate components of the biofilm matrix in the bacterial life have recently been studied (17,26,50,63). It is known that the matrix consists of proteins, polysaccharides, lipids, and nucleic acids, which form an extracellular polymeric substance (EPS) (21,34,56,64). Some suggest that EPS can interact with antibiotics in a manner that leads to a decline in antibacterial activity (5,8,29). It was also shown that bacterial survival in biofilms in the presence of antibiotics can be determined by special cells persisters, which are tolerant to various drugs (27,31,35,51). Recently, extracellular DNA has been found in the matrix of Pseudomonas aeruginosa and Neisseria gonorrhoeae biofilms (1,26,32,50,63). Previously, free circulating DNA was found in human blood plasma (3,45,61), and it is also present in marine sediments and soil (6,15,16,44,60). It was shown that the extracellular DNA in the biofilm matrix could take part in the development of bacterial communities (25,40,49,63). It can be released by live cells, possibly via membrane vesicles composed of bacterial lipids (65), or it may enter the matrix from lysed cells (10,18,19,48,58,65). We have recently found cell-free DNA as a component of EPS in biofilms formed by various unrelated gram-positive and gramnegative bacteria and fungi (G. Tetz and V. Tetz, unpublished data). It was previously shown that the destruction of the extracellular DNA of P. aeruginosa and Streptococcus pneumoniae could change the properties of the biofilms formed by these bacteria (30,40,63). At the same time, this phenomenon has not been studied with other microorganisms. The role of extracellular DNA in the interaction of bacterial biofilms with environmental factors i...

Increased intestinal permeability and translocation of gut bacteria trigger various polyaetiological diseases associated with chronic inflammation and underlie a variety of poorly treatable pathologies. Previous studies have established a primary role of the microbiota composition and intestinal permeability in such pathologies. Using a rat model, we examined the effects of exposure to a bacteriophage cocktail on intestinal permeability and relative abundance of taxonomic units in the gut bacterial community. There was an increase in markers of impaired gut permeability, such as the lactulose/mannitol ratio, plasma endotoxin concentrations, and serum levels of inflammation-related cytokines, following the bacteriophage challenge. We observed significant differences in the alpha diversity of faecal bacterial species and found that richness and diversity index values increased following the bacteriophage challenge. There was a reduction in the abundance of Blautia, Catenibacterium, Lactobacillus, and Faecalibacterium species and an increase in Butyrivibrio, Oscillospira and Ruminococcus after bacteriophage administration. These findings provide novel insights into the role of bacteriophages as potentially pathogenic for mammals and their possible implication in the development of diseases associated with increased intestinal permeability.

Based on their mode of action, which is different from that of clinically approved anti-HIV drugs, PDPs are good candidates for further development into new drugs and to be included in future combination regimens.

The pathogenesis of numerous human multifaceted devastating diseases, including a variety of neurodegenerative and autoimmune diseases, is associated with alterations in the gut microbiota; however, the underlying mechanisms are not completely understood. Our recent human metagenome and phagobiota proteome analyses and studies in relevant animal models suggested that bacterial viruses might be implicated in the progression and maintenance of at least some pathologies, including those associated with protein misfolding. Here, for the first time, we propose the concept of bacteriophages as human pathogens. We suggest that bacterial viruses have different ways to directly and indirectly interact with eukaryotic cells and proteins, leading to human diseases. Furthermore, we suggest different causes of bacteriophages infection on the basis of the unique ways of interplay of phages, microbiota, and the human host. This concept opens a discussion of the role of bacteriophages as previously overlooked pathogenic factors and suggests that bacterial viruses have to be further explored as a diagnostic and treatment target for therapeutic intervention.

Recent studies suggest that alterations in the gut phagobiota may contribute to pathophysiological processes in mammals; however, the association of bacteriophage community structure with Parkinson’s disease (PD) has not been yet characterized. Towards this end, we used a published dataset to analyse bacteriophage composition and determine the phage/bacteria ratio in faecal samples from drug-naive PD patients and healthy participants. Our analyses revealed significant alterations in the representation of certain bacteriophages in the phagobiota of PD patients. We identified shifts of the phage/bacteria ratio in lactic acid bacteria known to produce dopamine and regulate intestinal permeability, which are major factors implicated in PD pathogenesis. Furthermore, we observed the depletion of Lactococcus spp. in the PD group, which was most likely due to the increase of lytic c2-like and 936-like lactococcal phages frequently present in dairy products. Our findings add bacteriophages to the list of possible factors associated with the development of PD, suggesting that gut phagobiota composition may serve as a diagnostic tool as well as a target for therapeutic intervention, which should be confirmed in further studies. Our results open a discussion on the role of environmental phages and phagobiota composition in health and disease.