Bacteriophages (phages) have coevolved with their bacterial hosts for billions of years. With the rise of antibiotic resistance, the significance of using phages in therapy is increasing. Investigating the dynamics of phage evolution can provide valuable insights for pre-adapting phages to more challenging clones of their hosts that may arise during treatment. Two primary models describe interactions in phage–bacteria systems: arms race dynamics and fluctuating selection dynamics. Numerous factors influence which dynamics dominate the interactions between a phage and its host. These dynamics, in turn, affect the coexistence of phages and bacteria, ultimately determining which organism will adapt more effectively to the other, and whether a stable state will be reached. In this review, we summarize key findings from research on phage–bacteria coevolution, focusing on the different concepts that can describe these interactions, the factors that may contribute to the prevalence of one model over others, and the effects of various dynamics on both phages and bacteria.

Omsk hemorrhagic fever virus (OHFV) is a member of the tick-borne encephalitis virus (TBEV) complex of the Flaviviridae family. Currently, there are no data on the cross-reactivity of antibodies to the NS1 proteins of OHFV and TBEV. Such data are of major interest for monitoring viral encephalitis of unknown etiology due to the increasing geographical distribution of OHFV. In this study, a recombinant OHFV NS1 protein was produced using the Escherichia coli expression system and purified. The recombinant OHFV NS1 protein was recognized by specific mice immune ascetic fluids to the native OHFV NS1 protein. A Western blot analysis and ELISA of the recombinant NS1 proteins of OHFV and TBEV were used to study the cross-reactivity of antibodies from immune ascites fluid obtained from OHFV-infected mice and mAbs against TBEV NS1. Anti-TBEV NS1 mouse monoclonal antibodies (mAbs) have been shown to not be cross-reactive to the OHFV NS1 protein. Sera from patients with confirmed tick-borne encephalitis (TBE) were examined by ELISA using recombinant OHFV NS1 and TBEV NS1 proteins as antigens. It was shown for the first time that cross-reactive antibodies to the OHFV NS1 protein were not detected in the sera of TBE patients, whereas the sera contained antibodies to the TBEV NS1 protein.

Orthoflavivirus encephalitidis (tick-borne encephalitis virus, TBEV) is of high concern due to its ability to cause severe neurological manifestations. Despite the fact that the role of NS1 proteins from various mosquito-borne flaviviruses in pathogenesis and their ability to affect human endothelial permeability have been investigated, TBEV NS1 has thus far been insufficiently studied. In this study, human endothelial permeability was assessed using TEER and transwell permeability assays. Signaling pathways were determined by RNAseq. The ability of the NS1 protein of TBEV to affect human endothelial permeability was investigated for the first time. It was shown that recombinant TBEV NS1 produced in eucaryotic cells directly affected human lung microvascular endothelial cells (HLMVECs) in vitro but not human umbilical vein endothelial cells (HUVECs). It was indicated that TBEV NS1 induced endothelial hyperpermeability of HLMVECs through activating TNF-α and other inflammatory signaling pathways.

Klebsiella pneumoniae, a member of the ESKAPEE group of priority pathogens, has become one of the most challenging bacterial pathogens in modern clinical practice, largely due to its multidrug resistance and the immune-evasive effect of its capsular polysaccharide (CPS). Phage-encoded depolymerases, which selectively degrade the capsular polysaccharide, have emerged as promising antimicrobial agents capable of restoring bacterial susceptibility to both immune clearance and phage infection. The fragment corresponding to the C-terminal region of a putative depolymerase of bacteriophage KlebP_144, namely DepKP144ΔC, was cloned, expressed in E. coli, and purified using immobilized metal affinity chromatography. DepKP144ΔC displays an enzymatic activity against capsular polysaccharides of 100% K1 capsular-type strains and 85% K2 capsular-type strains, including classical and hypervirulent isolates. It was demonstrated that this protein is capable of inhibiting K. pneumoniae biofilm formation, but it is unable to disrupt mature biofilms. In vivo experiments using a murine K. pneumoniae infection model further confirmed its therapeutic potential: treatment with DepKP144ΔC improved survival rate in mice infected with K2-type K. pneumoniae, indicating significant attenuation of bacterial virulence. Therefore, these results demonstrate the potential role of the C-terminal domain of the bacteriophage KP144 tail-fiber protein in phage entry and show that its carbohydrate-recognition motifs possess enzymatic activity against the Klebsiella capsular polysaccharides.

Omsk hemorrhagic fever virus (OHFV) is a member of the tick-borne encephalitis virus (TBEV) complex of the Flaviviridae family. Currently, there is no data on cross-reactivity of antibodies to the NS1 proteins of OHFV and TBEV. Such data are of major interest for monitoring viral encephalitis of unknown etiology due to the increasing geographical distribution of OHFV. In this study, recombinant OHFV NS1 protein was produced using Escherichia сoli expression system and purified. The recombinant OHFV NS1 protein was recognized by specific mice immune ascetic fluids to the native OHFV NS1 protein. Western blot analysis and ELISA of recombinant NS1 proteins of OHFV and TBEV were used to study the cross-reactivity of antibodies from immune ascites fluid obtained from OHFV-infected mice and mAbs against TBEV NS1. Anti-TBEV NS1 mouse monoclonal antibodies (mAbs) have been shown not to be cross-reactive to OHFV NS1 protein. Sera from patients with confirmed tick-borne encephalitis (TBE) were examined by ELISA using recombinant OHFV NS1 and TBEV NS1 proteins as antigens. It was shown for the first time that cross-reactive antibodies to OHFV NS1 protein were not detected in the sera of TBE patients whereas the sera contained antibodies to TBEV NS1 protein.

Orthoflavivirus omskense (Omsk hemorrhagic fever virus, OHFV) is a tick-borne flavivirus that causes Omsk hemorrhagic fever (OHF), a severe zoonotic disease endemic to Western Siberia. Despite the fact that the role of NS1 proteins of various mosquito-borne flaviviruses in pathogenesis was investigated and their ability to affect human endothelial permeability was shown, the role of the NS1 protein of OHFV in pathogenesis is unstudied. In this work, the ability of OHFV NS1 to induce human endothelial permeability was investigated for the first time. It was shown that recombinant OHFV NS1 produced in eucaryotic cells directly affects both human lung microvascular endothelial cells (HLMVEC) and human umbilical vein endothelial cells (HUVEC) in vitro. RNAseq of endothelial cells treated with OHFV NS1 indicated that OHFV NS1 enhances the expression of genes associated with cellular stress responses, vascular signaling, and cell–cell junction regulation, resulting in a nonspecific increase in the endothelial permeability of various vessels. These results suggest that the NS1 protein may contribute to OHFV pathogenesis by disrupting endothelial barrier function and promoting vascular leakage, potentially playing a role in the hemorrhagic manifestations of Omsk hemorrhagic fever.