Viruses versus bacteria--novel approaches to phage therapy as a tool against multidrug-resistant pathogens

Viertel, Tania Mareike; Ritter, Klaus; Horz, Hans-Peter

doi:10.1093/jac/dku173

Cited by 203 publications

(166 citation statements)

References 117 publications

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“…Phage therapy research has forwarded strongly and is waiting for FDA approval [20]. WHO suggested that all countries should follow AMR Action Plan by increasing R and D for new therapeutic intervention as well as by reducing antibiotic use in human, food animal and agricultural land.…”

Section: Resultsmentioning

confidence: 99%

“…Very soon we made probe to locate mdr genes in many bacteria known as Southern hybridization (1970s) and also able to locate such genes in unknown plasmids by PCR reaction (1980s). Finally, di-deoxy Sanger DNA sequencing principle helped to understand genetic structure of mdr genes and their associated promoter-enhancerrepressor elements that were induced by antibiotics [6,20]. However, bacteria continued its mission to live in presence of antibiotics and created MDR conjugative plasmid combining R-plasmid with F'-plasmid generating a platform for more space for mdr genes in plasmid and more stability and also more active in participation of battle against antibiotics to transfer mdr genes to all resident intestinal bacteria to save symbiosis (Figure 3) ( Table 1).…”

Section: Insights In Biomedicine Issn 2572-5610mentioning

confidence: 99%

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Mechanisms of AMR: Bacteria Won the Battle Against Antibiotics

Ak¹

2017

Insights Biomed

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Section: Resultsmentioning

confidence: 99%

Section: Insights In Biomedicine Issn 2572-5610mentioning

confidence: 99%

Mechanisms of AMR: Bacteria Won the Battle Against Antibiotics

Ak¹

2017

Insights Biomed

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“…An alternative is to capitalize on the diversity of "living" agents and their potential to overcome the evolution of resistance in situ, or in treating previously evolved multi-drug resistant pathogens. Examples include lytic phages against pathogenic bacteria [56,57] A prime advantage of dynamic agents, and bacteriophages in particular, is self-amplification and adaptation to resistant hosts in situ. Because the diversity of phages is virtually limitless, they can be combined into cocktails to maximize overall strain coverage and impact on the target bacterium [48].…”

Section: Ecological and Evolutionary Wedges To Vanquish Diseasementioning

confidence: 99%

Six wedges to curing disease

Hochberg

2017

Preprint

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Abstract.One of the great challenges in ecology and evolutionary biology is to explain disease, whether caused by infectious agents such as parasites and pathogens, or by the deterioration or transformation of cellular behavior and function, a prime example of the latter being cancer. Decades of observation and research suggest that successfully treating disease requires insights into how the environment mediates the interactions between disease causing agents (DCAs) and diseased individuals. A major finding is that single factor, targeted therapies are not only likely to fail in controlling or eradicating many DCAs, but are also likely to select for resistance, reducing options for subsequent treatment attempts, and in cases of infectious DCAs, rendering therapeutic agents (e.g., antibiotics) obsolete.I argue that meeting the growing challenge of treating disease in agriculture and animal husbandry, in protected and domesticated species, wildlife, and in the human population will require a fundamental understanding of ecological interactions at sites of infection or disease. I discuss different ways in which components of such disease ecosystems mediate DCA and therapeutic dynamics and resistance evolution, and derive a very simple mathematical criterion for therapeutic success. I then touch on how fundamental insights as revealed by the processes of evolutionary rescue and competitive release can help understand why therapies succeed or fail. Finally, I present six "wedges" that can each contribute alone, or as part of multi-pronged approaches to successfully treating disease. The Magic BulletDespite remarkable progress in prevention and treatment, the impacts of diseases in agriculture and animal husbandry, and on protected and domesticated species, wildlife, and human health are likely to intensify into the 21 st century. Humans in particular are increasingly in contact with each other and with wildlife, treated with drug regimens that select for resistance, and adopt life-styles or are exposed to environments that render them more susceptible to infectious diseases and more likely to get cellular diseases such as cancers.For many clinicians the Holy Grail is to discover the Ehrlichian "Magic Bullet"-a drug that will target the disease-causing agents (DCAs) and cure disease. Intuitively, the most effective way to reduce DCAs is to "hit hard and fast". That is, more drug means more kill within the tolerance limits of the patient. Rapid administration of the drug means forestalling further DCA growth and associated symptoms, but also reducing the probability of the appearance of resistant mutant strains. Despite decades of research on pest and disease control (much of it with an ecological basis) this approach and the many alternatives described below remain highly controversial (e.g., [1]).The Magic Bullet may be shortsighted for another reason. What will cure most patients may not be optimal for the general population in which resistant variants may emerge and spread 1 . This problem is in many ways similar...

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“…Phage therapies can be effective against multidrug resistant bacteria, and, because of the high specificity of phages for given bacterial strains, they are unlikely to modify the host normal flora (Matsuzaki et al, 2014). Different strategies can be used in phage therapy (Viertel, Ritter, & Horz, 2014), including direct use of bacteriophages to target bacteria, engineered phages ( (Nobrega, Costa, Kluskens, & Azeredo, 2015); on the use of "phage cocktails", see (Chan, Abedon, & Loc-Carrillo, 2013)), combinations of phages with antimicrobial substances, the use of lytic enzymes (in particular endolysin, e.g., (Gupta & Prasad, 2011)), and the phagemediated prevention of antibiotic resistance. Interesting recent results in phage therapy have been found for several bacterial infections, including infections of the urinary/genital tract (Międzybrodzki et al, 2012) and pulmonary infections (Abedon, 2015); they could also play an important role in the gut to improve gut disorders (Dalmasso, Hill, & Ross, 2014 (Kingwell, 2015).…”

Section: Virotherapy: the Development Of New Therapeutic Approachesmentioning

confidence: 99%

Mutualistic viruses and the heteronomy of life

Pradeu

2016

Studies in History and Philosophy of Science Part C: Studies in

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Though viruses have generally been characterized by their pathogenic and more generally harmful effects, many examples of mutualistic viruses exist. Here I explain how the idea of mutualistic viruses has been defended in recent virology, and I explore four important conceptual and practical consequences of this idea. I ask to what extent this research modifies the way scientists might search for new viruses, our notion of how the host immune system interacts with microbes, the development of new therapeutic approaches, and, finally, the role played by the criterion of autonomy in our understanding of living things. Overall, I suggest that the recognition of mutualistic viruses plays a major role in a wider ongoing revision of our conception of viruses.

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Viruses versus bacteria--novel approaches to phage therapy as a tool against multidrug-resistant pathogens

Cited by 203 publications

References 117 publications

Mechanisms of AMR: Bacteria Won the Battle Against Antibiotics

Mechanisms of AMR: Bacteria Won the Battle Against Antibiotics

Six wedges to curing disease

Mutualistic viruses and the heteronomy of life

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