Lysis-deficient bacteriophage therapy decreases endotoxin and inflammatory mediator release and improves survival in a murine peritonitis model

Matsuda, Takeshi; Freeman, Tracy A.; Hilbert, David W.; Duff, Michael; Fuortes, Michele; Stapleton, Philip P.; Daly, J.M.

doi:10.1016/j.surg.2005.02.012

Cited by 105 publications

(77 citation statements)

References 26 publications

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“…At the same time, T4LyD-treated mice had lower endotoxin and cytokine (TNF-␣ and IL-6) levels 12 h after infection than the other groups, indicating that the systemic immunological side effects of phage therapy had been attenuated (138). Similar to the results obtained with M13S105 and Pf3R, the effectiveness of T4LyD suggests that converting lytic to nonlytic phages is a fruitful strategy for reducing their immunological effects.…”

Section: Engineered Phages With Reduced Impacts On Mammalian Systemssupporting

confidence: 58%

“…Similarly, Matsuda et al (138) showed that treating E. coli peritonitis in mice with the lysis-deficient phage T4LyD significantly increased the survival rate (81% survival at 48 h) compared to that of mice treated with the wild-type phage (52% survival), mice treated with the ␤-lactam moxalactam sodium (33% survival), or control untreated mice, which died within 20 h (138). At the same time, T4LyD-treated mice had lower endotoxin and cytokine (TNF-␣ and IL-6) levels 12 h after infection than the other groups, indicating that the systemic immunological side effects of phage therapy had been attenuated (138).…”

Section: Engineered Phages With Reduced Impacts On Mammalian Systemsmentioning

confidence: 97%

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Genetically Engineered Phages: a Review of Advances over the Last Decade

Pires

Cleto

Sillankorva

et al. 2016

Microbiol Mol Biol Rev

324

275

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SUMMARYSoon after their discovery in the early 20th century, bacteriophages were recognized to have great potential as antimicrobial agents, a potential that has yet to be fully realized. The nascent field of phage therapy was adversely affected by inadequately controlled trials and the discovery of antibiotics. Although the study of phages as anti-infective agents slowed, phages played an important role in the development of molecular biology. In recent years, the increase in multidrug-resistant bacteria has renewed interest in the use of phages as antimicrobial agents. With the wide array of possibilities offered by genetic engineering, these bacterial viruses are being modified to precisely control and detect bacteria and to serve as new sources of antibacterials. In applications that go beyond their antimicrobial activity, phages are also being developed as vehicles for drug delivery and vaccines, as well as for the assembly of new materials. This review highlights advances in techniques used to engineer phages for all of these purposes and discusses existing challenges and opportunities for future work.

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Section: Engineered Phages With Reduced Impacts On Mammalian Systemssupporting

confidence: 58%

Section: Engineered Phages With Reduced Impacts On Mammalian Systemsmentioning

confidence: 97%

Genetically Engineered Phages: a Review of Advances over the Last Decade

Pires

Cleto

Sillankorva

et al. 2016

Microbiol Mol Biol Rev

324

275

View full text Add to dashboard Cite

show abstract

“…The science behind phage therapy is still in its early stages, however, and general principles that determine treatment success and failure are hard to identify. Perhaps the most oft-assumed principle is that the rate at which phages kill bacteria is critical to success; the principle underlies all theoretical endeavors into phage therapy (7,14,15,22,23) and several experimental ones (9,13,17,20,30,31).…”

Section: Discussionmentioning

confidence: 99%

In VivoGrowth Rates Are Poorly Correlated with Phage Therapy Success in a Mouse Infection Model

Bull

Otto

Molineux

2012

Antimicrob Agents Chemother

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Two classes of phages yield profoundly different levels of recovery in mice experimentally infected with an Escherichia coli O18: K1:H7 strain. Phages requiring the K1 capsule for infection (K1-dep) rescue virtually all infected mice, whereas phages not requiring the capsule (K1-ind) rescue modest numbers (ϳ30%). To rescue infected mice, K1-ind phages require at least a 10 6 -foldhigher inoculum than K1-dep phages. Yet their in vivo growth dynamics are only modestly inferior to those of K1-dep phages, and competition between the two phage types in the same mouse reveals only a slight growth advantage for the K1-dep phage. The in vivo growth rate seems unlikely to be the primary determinant of phage therapy success. An alternative explanation is that the success of K1-dep phages is due substantially to their proteomic composition. They encode an enzyme that degrades the K1 capsule, which has been shown in other work to be sufficient to cure infection in the complete absence of phages.

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“…Consideration should be given to the potential release of endotoxin caused by bacteriophage-induced lysis, which may stimulate an inflammatory response. However, an endotoxin removal kit that can be used for clinical trials has been developed to overcome this potential problem (Matsuda et al 2005;Merabishvili et al 2009). Furthermore, Hagens and Bläsi (2003) engineered filamentous phages that could be toxic to bacteria but do not cause cell lysis, thus reducing the chance of endotoxin release.…”

Section: Bacteriophage Applicationsmentioning

confidence: 99%

Bacteriophages: the possible solution to treat infections caused by pathogenic bacteria

El‐Shibiny

El-Sahhar

2017

Can. J. Microbiol.

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Since their discovery in 1915, bacteriophages have been used to treat bacterial infections in animals and humans because of their unique ability to infect their specific bacterial hosts without affecting other bacterial populations. The research carried out in this field throughout the 20th century, largely in Georgia, part of USSR and Poland, led to the establishment of phage therapy protocols. However, the discovery of penicillin and sulfonamide antibiotics in the Western World during the 1930s was a setback in the advancement of phage therapy. The misuse of antibiotics has reduced their efficacy in controlling pathogens and has led to an increase in the number of antibiotic-resistant bacteria. As an alternative to antibiotics, bacteriophages have become a topic of interest with the emergence of multidrug-resistant bacteria, which are a threat to public health. Recent studies have indicated that bacteriophages can be used indirectly to detect pathogenic bacteria or directly as biocontrol agents. Moreover, they can be used to develop new molecules for clinical applications, vaccine production, drug design, and in the nanomedicine field via phage display.Key words: bacteriophages, antibiotics, biocontrol, infection, pathogenesis.Résumé : Les bactériophages ont été utilisés pour traiter des infections bactériennes chez l'animal et l'humain depuis leur découverte en 1915, à cause de leur capacité unique d'infecter leurs hôtes bactériens spécifiques, sans affecter les autres populations bactériennes. La recherche réalisée dans ce domaine au cours du vingtième siècle, principalement en Géorgie, dans une partie de l'URSS et en Pologne, a mené à l'établissement de protocoles thérapeutiques à partir de phages. Cependant, la découverte de la pénicilline et des antibiotiques sulfamidés au cours des années 1930 a retardé l'avancement de la thérapie par les phages. Le mauvais usage des antibiotiques depuis leur découverte a résulté en une augmentation du nombre de bactéries résistantes aux antibiotiques et une réduction de leur efficacité à contrôler d'importants pathogènes. Les bactériophages sont devenus un sujet d'intérêt comme alternative aux antibiotiques avec l'émergence de bactéries multirésistantes qui constituent une menace à la santé publique. Des études récentes ont indiqué que les bactériophages peuvent être utilisés indirectement pour détecter les bactéries pathogènes, ou directement, comme agents de contrôle biologique. De plus, ils peuvent être utilisés pour développer de nouvelles molécules à des fins d'applications cliniques, de production de vaccins, dans la conception de médicaments et dans le domaine de la nanomédecine, par l'exposition sur phage. [Traduit par la Rédaction]

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Lysis-deficient bacteriophage therapy decreases endotoxin and inflammatory mediator release and improves survival in a murine peritonitis model

Cited by 105 publications

References 26 publications

Genetically Engineered Phages: a Review of Advances over the Last Decade

Genetically Engineered Phages: a Review of Advances over the Last Decade

In VivoGrowth Rates Are Poorly Correlated with Phage Therapy Success in a Mouse Infection Model

Bacteriophages: the possible solution to treat infections caused by pathogenic bacteria

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