Comprehensive Characterization of a Novel Bacteriophage, vB_VhaS_MAG7 against a Fish Pathogenic Strain of Vibrio harveyi and Its In Vivo Efficacy in Phage Therapy Trials.

Vibrio harveyi, a significant opportunistic marine pathogen, has been a challenge to the aquaculture industry, leading to severe economical and production losses. Phage therapy has been an auspicious approach in controlling such bacterial infections in the era of antimicrobial resistance. In this study, we isolated and fully characterized a novel strain-specific phage, vB_VhaS_MAG7, which infects V. harveyi MM46, and tested its efficacy as a therapeutic agent in challenged gilthead seabream larvae. vB_VhaS_MAG7 is a tailed bacteriophage with a double-stranded DNA of 49,315 bp. No genes linked with virulence or antibiotic resistance were harbored in the genome. The phage had a remarkably large burst size of 1393 PFU cell-1 and showed strong lytic ability in in vitro assays. When applied in phage therapy trials in challenged gilthead seabream larvae, vB_VhaS_MAG7 was capable of improving the survival of the larvae up to 20%. Due to its distinct features and safety, vB_VhaS_MAG7 is considered a suitable candidate for applied phage therapy.

Cyld restrains the hyperactivation of synovial fibroblasts in inflammatory arthritis by regulating the TAK1/IKK2 signaling axis.

TNF is a potent cytokine known for its involvement in physiology and pathology. In Rheumatoid Arthritis (RA), persistent TNF signals cause aberrant activation of synovial fibroblasts (SFs), the resident cells crucially involved in the inflammatory and destructive responses of the affected synovial membrane. However, the molecular switches that control the pathogenic activation of SFs remain poorly defined. Cyld is a major component of deubiquitination (DUB) machinery regulating the signaling responses towards survival/inflammation and programmed necrosis that induced by cytokines, growth factors and microbial products. Herein, we follow functional genetic approaches to understand how Cyld affects arthritogenic TNF signaling in SFs. We demonstrate that in spontaneous and induced RA models, SF-Cyld DUB deficiency deteriorates arthritic phenotypes due to increased levels of chemokines, adhesion receptors and bone-degrading enzymes generated by mutant SFs. Mechanistically, Cyld serves to restrict the TNF-induced hyperactivation of SFs by limiting Tak1-mediated signaling, and, therefore, leading to supervised NF-κB and JNK activity. However, Cyld is not critically involved in the regulation of TNF-induced death of SFs. Our results identify SF-Cyld as a regulator of TNF-mediated arthritis and inform the signaling landscape underpinning the SF responses.

Vibrio Phage Artemius, a Novel Phage Infecting Vibrio alginolyticus.

Vibrio alginolyticus is an important pathogen of marine animals and has been the target of phage therapy applications in marine aquaculture for many years. Here, we report the isolation and partial characterization of a novel species of the Siphoviridae family, the Vibrio phage Artemius. The novel phage was species-specific and could only infect strains of V. alginolyticus. It could efficiently reduce the growth of the host bacterium at various multiplicities of infection as assessed by an in vitro lysis assay. It had a genome length of 43,349 base pairs. The complete genome has double-stranded DNA with a G + C content of 43.61%. In total, 57 ORFs were identified, of which 19 were assigned a predicted function. A genomic analysis indicated that Vibrio phage Artemius is lytic and does not harbor genes encoding toxins and antibiotic resistance determinants.