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.

Recently, a Salmonella Typhi isolate producing CTX-M-15 extended spectrum β-lactamase (ESBL) and with decreased ciprofloxacin susceptibility was isolated in the Democratic Republic of the Congo. We have selected bacteriophages that show strong lytic activity against this isolate and have potential for phage-based treatment of S. Typhi, and Salmonella in general.

Non-typhoidal Salmonella present a major threat to animal and human health as food-borne infectious agents. We characterized 91 bacterial isolates from Armenia and Georgia in detail, using a suite of assays including conventional microbiological methods, determining antimicrobial susceptibility profiles, matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry, serotyping (using the White-Kauffmann-Le Minor scheme) and genotyping (repetitive element sequence-based PCR (rep-PCR)). No less than 61.5% of the isolates were shown to be multidrug-resistant. A new antimicrobial treatment strategy is urgently needed. Phage therapy, the therapeutic use of (bacterio-) phages, the bacterial viruses, to treat bacterial infections, is increasingly put forward as an additional tool for combatting antibiotic resistant infections. Therefore, we used this representative set of well-characterized Salmonella isolates to analyze the therapeutic potential of eleven single phages and selected phage cocktails from the bacteriophage collection of the Eliava Institute (Georgia). All isolates were shown to be susceptible to at least one of the tested phage clones or their combinations. In addition, genome sequencing of these phages revealed them as members of existing phage genera (Felixounavirus, Seunavirus, Viunavirus and Tequintavirus) and did not show genome-based counter indications towards their applicability against non-typhoidal Salmonella in a phage therapy or in an agro-food setting.

A total of 291 non-duplicate isolates of non-typhoidal Salmonella (NTS) were collected from the fecal samples of patients with salmonellosis in Armenia and Georgia during 1996–2016. The isolates were tested for resistance to antimicrobials, including extended-spectrum β-lactamases (ESBL). The high prevalence of multidrug-resistance (MDR) and ESBL-producer phenotypes was detected among Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) isolates collected from patients in Armenia between 1996 and 2016. A total of 36 MDR NTS isolates were subjected to whole genome sequencing (WGS) to determine the genetic background of antimicrobial resistance (AMR) and mobile genetic elements. All ESBL-producing S. Typhimurium isolates belonged to the same sequence type (ST328). The ESBL-producer phenotype was associated with plasmid-encoded CTX-M-5 production. A range of other plasmids was associated with resistance to other antimicrobials, including the MDR phenotype.

Since the beginning of the 20th century, bacteriophages (phages), i.e., viruses that infect bacteria, have been used as antimicrobial agents for treating various infections. Phage preparations targeting a number of bacterial pathogens are still in use in the post-Soviet states and are experiencing a revival in the Western world. However, phages have never been used to treat diseases caused by Bacteroides fragilis, the leading agent cultured in anaerobic abscesses and postoperative peritonitis. Enterotoxin-producing strains of B. fragilis have been associated with the development of inflammatory diarrhea and colorectal carcinoma. In this study, we evaluated the molecular biosafety and antimicrobial properties of novel phage species vB_BfrS_VA7 (VA7) lysate, as well as its impact on cytokine IL-8 production in an enterotoxigenic B. fragilis (ETBF)-infected colonic epithelial cell (CEC) culture model. Compared to untreated infected cells, the addition of phage VA7 to ETBF-infected CECs led to significantly reduced bacterial counts and IL-8 levels. This in vitro study confirms the potential of phage VA7 as an antibacterial agent for use in prophylaxis or in the treatment of B. fragilis infections and associated colorectal carcinoma.

Aims This paper presents the potential of environmentally sourced bacteriophages to affect the growth of clinical isolates of Pseudomonas aeruginosa biofilms, and assesses the respective plaque morphotypes presented by each bacteriophage, in vitro. Methods and Results Bacterial host strains were typed for their ability to produce the quorum sensing‐controlled virulence factor pyocyanin, and then tested for bacteriophage susceptibility using the spot test method. The bacteriophages were co‐administered with ciprofloxacin in order to determine whether the bacteriophages would demonstrate synergistic or antagonistic behaviour to the antibiotic in vitro. Results suggest a potential relationship between the bacteriophage plaque size and biofilm inhibition, where those producing smaller plaques appear to be more effective at reducing bacterial biofilm formation. Conclusions This phenomenon may be explained by a high adsorption rate leading to the rapid formation of smaller plaques, and greater biofilm reduction associated with the loss of viable bacterial cells before the cells can adhere to the surface and form a biofilm. Results from the co‐administration of bacteriophage and ciprofloxacin suggest that the two work synergistically to affect P. aeruginosa biofilms. Significance and Impact of the Study The data indicate enhanced efficacy of ciprofloxacin by ≥50%. This could offer an alternative strategy for targeting antibiotic‐resistant infections.

Bacteriophages that lyse Salmonella enterica are potential tools to target and control Salmonella infections. Investigating the host range of Salmonella phages is a key to understand their impact on bacterial ecology, coevolution and inform their use in intervention strategies. Virus–host infection networks have been used to characterize the “predator–prey” interactions between phages and bacteria and provide insights into host range and specificity. Here, we characterize the target-range and infection profiles of 13 Salmonella phage clones against a diverse set of 141 Salmonella strains. The environmental source and taxonomy contributed to the observed infection profiles, and genetically proximal phages shared similar infection profiles. Using in vitro infection data, we analyzed the structure of the Salmonella phage–bacteria infection network. The network has a non-random nested organization and weak modularity suggesting a gradient of target-range from generalist to specialist species with nested subsets, which are also observed within and across the different phage infection profile groups. Our results have implications for our understanding of the coevolutionary mechanisms shaping the ecological interactions between Salmonella phages and their bacterial hosts and can inform strategies for targeting Salmonella enterica with specific phage preparations.

No abstract