Phage therapy is increasingly put forward as a “new” potential tool in the fight against antibiotic resistant infections. During the “Centennial Celebration of Bacteriophage Research” conference in Tbilisi, Georgia on 26–29 June 2017, an international group of phage researchers committed to elaborate an expert opinion on three contentious phage therapy related issues that are hampering clinical progress in the field of phage therapy. This paper explores and discusses bacterial phage resistance, phage training and the presence of prophages in bacterial production strains while reviewing relevant research findings and experiences. Our purpose is to inform phage therapy stakeholders such as policy makers, officials of the competent authorities for medicines, phage researchers and phage producers, and members of the pharmaceutical industry. This brief also points out potential avenues for future phage therapy research and development as it specifically addresses those overarching questions that currently call for attention whenever phages go into purification processes for application.

A mixed culture dechlorinating 1,2-dichloroethane (1,2-DCA) to ethene was enriched from groundwater that had been subjected to long-term contamination. In the metagenome of the enrichment, a 7-kb reductive dehalogenase (RD) gene cluster sequence was detected by inverse and direct PCR. The RD gene cluster had four open reading frames (ORF) showing 99% nucleotide identity with pceB, pceC, pceT, and orf1 of Dehalobacter restrictus strain DSMZ 9455 T , a bacterium able to dechlorinate chlorinated ethenes. However, dcaA, the ORF encoding the catalytic subunit, showed only 94% nucleotide and 90% amino acid identity with pceA of strain DSMZ 9455 T . Fifty-three percent of the amino acid differences were localized in two defined regions of the predicted protein. Exposure of the culture to 1,2-DCA and lactate increased the dcaA gene copy number by 2 log units, and under these conditions the dcaA and dcaB genes were actively transcribed. A very similar RD gene cluster with 98% identity in the dcaA gene sequence was identified in Desulfitobacterium dichloroeliminans strain DCA1, the only known isolate that selectively dechlorinates 1,2-DCA but not chlorinated ethenes. The dcaA gene of strain DCA1 possesses the same amino acid motifs as the new dcaA gene. Southern hybridization using total genomic DNA of strain DCA1 with dcaA gene-specific and dcaB-and pceB-targeting probes indicated the presence of two identical or highly similar dehalogenase gene clusters. In conclusion, these data suggest that the newly described RDs are specifically adapted to 1,2-DCA dechlorination.Chlorinated alkanes are prevailing groundwater contaminants in many industrialized countries (www.epa.gov/enviro /html/tris/ez.html), and they cause serious environmental problems (14). Among these, 1,2-dichloroethane (1,2-DCA) represents one of the world's most important toxic C 2 chlorinated aquifer pollutants. From 1987 to 1993, over 209 tons of 1,2-DCA were released into groundwater (www.epa.gov/enviro /html/tris/ez.html). Enhancement of natural attenuation processes can play a major role in achieving remediation, where applicable (17, 30), and often bioremediation alone or in combination with physical treatment of the most contaminated areas could represent the most convenient solution. The main catalyzers of the bioremediation processes are microorganisms that can dehalogenate and/or mineralize the toxic molecules with their enzymatic systems (12,40).A metabolic process of particular interest is based on dehalorespiration, a reaction that couples reductive dehalogenation with energy conservation (11,35,40). Dehalorespiration is one of the key processes for the remediation of polluted groundwaters (20,24,25). The key catalysts in dehalorespiration are reductive dehalogenases (RDs), membrane-associated enzymes with low levels of nucleotide identity but with some common traits, such as two iron-sulfur clusters as prosthetic groups, a twin-arginine translocation signal peptide (TAT system), and corrinoid cofactors (22). Recently, it has been reported that ...

In this chapter we review bacteriophage production requirements to help institutions, which wish to manufacture bacteriophage products for human use in compliance with the applicable regulatory expectancies, defining production processes and implementing relevant controls ensuring quality, safety, and efficacy of the final products. The information disclosed in this chapter can also serve as a basis for discussions with competent authorities regarding the development of expedited bacteriophage product development and licensing pathways, including relevant and pragmatic requirements, and allowing for the full exploitation of bacteriophages as natural controllers of bacterial populations.

The transport and activity of Desulfitobacterium dichloroeliminans strain DCA1 in 1,2-dichloroethane (1,2-DCA)-contaminated groundwater have been evaluated through an in situ bioaugmentation test at an industrial site (Belgium). The migration of strain DCA1 was monitored from an injection well toward a monitoring well, and the effect of the imposed groundwater flow on its distribution was assessed by means of transport model MOCDENS3D. The results of the real-time PCR (16S rRNA gene) quantification downstream from the injection point were used to evaluate the bacterial distribution pattern simulated by MOCDENS3D. In the injection well, the 1,2-DCA concentration in the groundwater decreased from 939.8 to 0.9 microM in a 35 day time interval and in the presence of a sodium lactate solution. Moreover, analyses from the monitoring well showed that the cells were still active after transport through the aquifer, although biodegradation occurred to a lesser extent. This study showed that strain DCA1 can be successfully applied for the removal of 1,2-DCA under field conditions and that its limited retardation offers perspectives for large-scale cleanup processes of industrial sites.

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