On the Interactions between Virulent Bacteriophages and Bacteria in the gut

We recently described the targeting of O104:H4 Escherichia coli in mouse gut by several virulent bacteriophages, highlighting several issues relating to virus-host interactions, which we discuss further in this addendum to the original publication

Pulmonary Bacteriophage Therapy on Pseudomonas aeruginosa Cystic Fibrosis Strains: First Steps Towards Treatment and Prevention

Multidrug-resistant bacteria are the cause of an increasing number of deadly pulmonary infections. Because there is currently a paucity of novel antibiotics, phage therapy—the use of specific viruses that infect bacteria—is now more frequently being considered as a potential treatment for bacterial infections. Using a mouse lung-infection model caused by a multidrug resistant Pseudomonas aeruginosa mucoid strain isolated from a cystic fibrosis patient, we evaluated bacteriophage treatments. New bacteriophages were isolated from environmental samples and characterized. Bacteria and bacteriophages were applied intranasally to the immunocompetent mice. Survival was monitored and bronchoalveolar fluids were analysed. Quantification of bacteria, bacteriophages, pro-inflammatory and cytotoxicity markers, as well as histology and immunohistochemistry analyses were performed. A curative treatment (one single dose) administrated 2 h after the onset of the infection allowed over 95% survival. A four-day preventive treatment (one single dose) resulted in a 100% survival. All of the parameters measured correlated with the efficacy of both curative and preventive bacteriophage treatments. We also showed that in vitro optimization of a bacteriophage towards a clinical strain improved both its efficacy on in vivo treatments and its host range on a panel of 20 P. aeruginosa cystic fibrosis strains. This work provides an incentive to develop clinical studies on pulmonary bacteriophage therapy to combat multidrug-resistant lung infections

Repetitive Exposure to Bacteriophage Cocktails against Pseudomonas aeruginosa or Escherichia coli Provokes Marginal Humoral Immunity in Naïve Mice

Phage therapy of ventilator-associated pneumonia (VAP) is of great interest due to the rising incidence of multidrug-resistant bacterial pathogens. However, natural or therapy-induced immunity against therapeutic phages remains a potential concern. In this study, we investigated the innate and adaptive immune responses to two different phage cocktails targeting either Pseudomonas aeruginosa or Escherichia coli—two VAP-associated pathogens—in naïve mice without the confounding effects of a bacterial infection. Active or UV-inactivated phage cocktails or buffers were injected intraperitoneally daily for 7 days in C57BL/6J wild-type mice. Blood cell analysis, flow cytometry analysis, assessment of phage distribution and histopathological analysis of spleens were performed at 6 h, 10 days and 21 days after treatment start. Phages reached the lungs and although the phage cocktails were slightly immunogenic, phage injections were well tolerated without obvious adverse effects. No signs of activation of innate or adaptive immune cells were observed; however, both active phage cocktails elicited a minimal humoral response with secretion of phage-specific antibodies. Our findings show that even repetitive injections lead only to a minimal innate and adaptive immune response in naïve mice and suggest that systemic phage treatment is thus potentially suitable for treating bacterial lung infections

The phage therapy paradigm: prêt-à-porter or sur-mesure?

The present opinion is the result of discussions on the future of phage therapy (personalized or large-scale uniform therapy?) during the first International Congress on Viruses of Microbes, held at the Institut Pasteur in Paris on June 21–25, 2010

La phagothérapie expérimentale à l’aube du xxie siècle

International audiencePhage therapy was gradually abandoned in the middle of the 20th century, and the scientific community has since disregarded this therapeutic approach. Then, at the end of the 20th century, pushed by the necessity to find new solutions to the rapid increase of antibiotic resistant bacteria, some scientists came back to phage therapy. If between 1980 and 2000, the number of scientific articles was low, a substantial increase was noted over the past five years. This is a review of the most recent articles, pointing out new data and questions still to be addressed.Après le déclin de l'utilisation de la phagothérapie en Occident au milieu du xx e siècle, la communauté scientifique occidentale s'est désintéressée de cette approche thérapeutique. Puis, à la fin du xx e siècle, poussés par la nécessité de trouver des solutions originales à l'émergence rapide de la résistance aux antibiotiques, certains scientifiques se sont à nouveau tournés vers la phagothérapie. Si entre les années 1980 et 2000, le nombre des articles scientifiques est resté faible, on a pu noter une augmentation notable de ceux-ci au cours des cinq dernières années. Cette revue a pour but de synthétiser les articles les plus récents afin d'en faire ressortir les principaux acquis et les questions encore en suspens

Bacterial sensing of bacteriophages in communities: the search for the Rosetta stone.

International audienceBillions of years of evolution have resulted in microbial viruses and their hosts communicating in such a way that neither of these antagonists can dominate the other definitively. Studies of the molecular mechanisms underlying this dialog, initially in bacteriophages, rapidly identified several of the ways in which bacteria resist bacteriophage infections and bacteriophages defeat bacterial defenses. From an ecological perspective, recent data have raised many questions about the dynamic interactions between bacteria and bacteriophages, the densities of which, in complex microbial populations, are only beginning to be investigated. The next challenge will be determining how the dialog between microbial viruses and their hosts modulates complex ecosystems, such as those found in healthy humans or infected patients

Electron Avenue: Pathways of Disulfide Bond Formation and Isomerization

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La phagothérapie : Une arme crédible face à l’antibiorésistance

International audienceThe continuous increase in antibiotic resistance among bacteria in infectious diseases associated with the lack of new antibiotics able to circumvent them are urging physicians, researchers and politicians to look for others options for treatments. Among those, phage therapy (use of natural viruses that infect bacteria, called bacteriophages) is one of the most promising approaches. In this review, we first focus on the problematic raised by multidrug resistant bacteria before addressing the main biological characteristics of bacteriophages, as well as the credibility and the relevance of phage therapy. We then introduce human applications, their potentials and limits

Bacteriophages as twenty-first century antibacterial tools for food and medicine.

International audienceAntibiotic-resistant bacteria are an increasing source of concern in all environments in which these drugs have been used. More stringent regulations have led to a slow but sure decrease in antibiotic use in the food industry worldwide, but have also stimulated the search for alternative antibacterial agents. In medicine, the number of people infected with pan-resistant bacteria is driving research to develop new treatments. Within these contexts, studies on the use of bacteriophages in both medicine and the food industry have recently flourished. This renewed interest has coincided with the demonstration that these viruses are involved in geochemical cycles, revolutionizing our vision of their ecological role on our planet. Bacteriophages have co-evolved with bacteria for billions of years and retain the ability to infect bacteria efficiently. They are undoubtedly one of the best potential sources of new solutions for the management of undesirable bacteria