Clinical Potential of Bacteriophage and Endolysin Based Therapeutics: A Futuristic Approach
01 Jan 2021-pp 39-58
TL;DR: The present chapter will highlight the features of bacteriophage and endolysin that make them attractive and effective long-term therapeutic alternatives for the treatment of drug-resistant infections in clinical settings.
Abstract: Antibiotic resistance is a global health challenge in the modern era. The emergence of antibiotic-resistant strains poses a serious threat to human health across the globe and compromises the arsenal of antibiotics upon which the modern healthcare system heavily relies. Antibiotic resistance diminishes the choice for effective antimicrobial agents and forces researchers to look for effective alternative agents. Bacteriophages have been established as potent antibacterial agents against most of the bacterial pathogens since the pre-antibiotic era. Additionally, the discovery and exploration of endolysins, i.e. phage coded peptidoglycan hydrolases, have further revolutionized the field of phage-based therapy. Bacteriophage and endolysin have demonstrated to be effective for clearing the infection in both in vitro and in vivo models. Nevertheless, there is a scarcity of information on the clinical potential of bacteriophage and endolysin. The present chapter will highlight the features of bacteriophage and endolysin that make them attractive and effective long-term therapeutic alternatives for the treatment of drug-resistant infections in clinical settings.
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12 Aug 2016
TL;DR: In this article, the authors proposed a hybrid threshold adaptable quantum secret sharing scheme, using an m-bonacci orbital angular momentum (OAM) pump, Lagrange interpolation polynomials, and reverse Huffman-Fibonacci-tree coding.
Abstract: With prevalent attacks in communication, sharing a secret between communicating parties is an ongoing challenge. Moreover, it is important to integrate quantum solutions with classical secret sharing schemes with low computational cost for the real world use. This paper proposes a novel hybrid threshold adaptable quantum secret sharing scheme, using an m-bonacci orbital angular momentum (OAM) pump, Lagrange interpolation polynomials, and reverse Huffman-Fibonacci-tree coding. To be exact, we employ entangled states prepared by m -bonacci sequences to detect eavesdropping. Meanwhile, we encode m -bonacci sequences in Lagrange interpolation polynomials to generate the shares of a secret with reverse Huffman-Fibonacci-tree coding. The advantages of the proposed scheme is that it can detect eavesdropping without joint quantum operations, and permits secret sharing for an arbitrary but no less than threshold-value number of classical participants with much lower bandwidth. Also, in comparison with existing quantum secret sharing schemes, it still works when there are dynamic changes, such as the unavailability of some quantum channel, the arrival of new participants and the departure of participants. Finally, we provide security analysis of the new hybrid quantum secret sharing scheme and discuss its useful features for modern applications.
400 citations
TL;DR: In this article , a review extensively summarizes preclinical phage therapy approaches in various in-vivo models and present the current state of PT and considered how animal models can be used to adapt these therapies for humans.
Abstract: ABSTRACT The rapid increase in antibiotic resistance presents a dire situation necessitating the need for alternative therapeutic agents. Among the current alternative therapies, phage therapy (PT) is promising. This review extensively summarizes preclinical PT approaches in various in-vivo models. PT has been evaluated in several recent clinical trials. However, there are still several unanswered concerns due to a lack of appropriate regulation and pharmacokinetic data regarding the application of phages in human therapeutic procedures. In this review, we also presented the current state of PT and considered how animal models can be used to adapt these therapies for humans. The development of realistic solutions to circumvent these constraints is critical for advancing this technology.
2 citations
TL;DR: In this article , the authors described the biological characteristics of bacteriophage, and summarized the phage application in China, including in mammals, ovipara, aquatilia, and human clinical treatment.
Abstract: Antibiotic resistance has emerged as a significant issue to be resolved around the world. Bacteriophage (phage), in contrast to antibiotics, can only kill the target bacteria with no adverse effect on the normal bacterial flora. In this review, we described the biological characteristics of phage, and summarized the phage application in China, including in mammals, ovipara, aquatilia, and human clinical treatment. The data showed that phage had a good therapeutic effect on drug-resistant bacteria in veterinary fields, as well as in the clinical treatment of humans. However, we need to take more consideration of the narrow lysis spectrum, the immune response, the issues of storage, and the pharmacokinetics of phages. Due to the particularity of bacteriophage as a bacterial virus, there is no unified standard or regulation for the use of bacteriophage in the world at present, which hinders the application of bacteriophage as a substitute for antibiotic biological products. We aimed to highlight the rapidly advancing field of phage therapy as well as the challenges that China faces in reducing its reliance on antibiotics.
1 citations
References
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TL;DR: It is found that intraflagellar transport 20 mediates the ability of Ror2 signaling to induce the invasiveness of tumors that lack primary cilia, and IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex.
Abstract: Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion. Furthermore, IFT20 promotes the efficiency of transport through the Golgi complex. These findings shed new insights into how Ror2 signaling promotes tumor invasiveness, and also advance the understanding of how Golgi structure and transport can be regulated.
13,354 citations
TL;DR: The data further characterize the ultrastructural analysis of the KD mouse model, and support recent theories of a dying-back mechanism for neuronal degeneration, which is independent of demyelination.
Abstract: Krabbe disease (KD) is a neurodegenerative disorder caused by the lack of β- galactosylceramidase enzymatic activity and by widespread accumulation of the cytotoxic galactosyl-sphingosine in neuronal, myelinating and endothelial cells. Despite the wide use of Twitcher mice as experimental model for KD, the ultrastructure of this model is partial and mainly addressing peripheral nerves. More details are requested to elucidate the basis of the motor defects, which are the first to appear during KD onset. Here we use transmission electron microscopy (TEM) to focus on the alterations produced by KD in the lower motor system at postnatal day 15 (P15), a nearly asymptomatic stage, and in the juvenile P30 mouse. We find mild effects on motorneuron soma, severe ones on sciatic nerves and very severe effects on nerve terminals and neuromuscular junctions at P30, with peripheral damage being already detectable at P15. Finally, we find that the gastrocnemius muscle undergoes atrophy and structural changes that are independent of denervation at P15. Our data further characterize the ultrastructural analysis of the KD mouse model, and support recent theories of a dying-back mechanism for neuronal degeneration, which is independent of demyelination.
10,233 citations
TL;DR: This work experimentally demonstrates an electronically-tunable terahertz intensity modulator based on Bi1:5Sb0:5Te1:8Se1:2 single crystal, one of the most insulating topological insulators, and proposes that the extraordinarily large modulation is a consequence of thermally-activated carrier absorption in the semiconducting bulk states.
Abstract: Three dimensional topological insulators, as a new phase of quantum matters, are characterized by an insulating gap in the bulk and a metallic state on the surface. Particularly, most of the topological insulators have narrow band gaps, and hence have promising applications in the area of terahertz optoelectronics. In this work, we experimentally demonstrate an electronically-tunable terahertz intensity modulator based on Bi1:5Sb0:5Te1:8Se1:2 single crystal, one of the most insulating topological insulators. A relative frequency-independent modulation depth of ~62% over a wide frequency range from 0.3 to 1.4 THz has been achieved at room temperature, by applying a bias current of 100 mA. The modulation in the low current regime can be further enhanced at low temperature. We propose that the extraordinarily large modulation is a consequence of thermally-activated carrier absorption in the semiconducting bulk states. Our work provides a new application of topological insulators for terahertz technology.
982 citations
TL;DR: A novel hybrid threshold adaptable quantum secret sharing scheme, using an m-bonacci orbital angular momentum pump, Lagrange interpolation polynomials, and reverse Huffman-Fibonacci-tree coding, which can detect eavesdropping without joint quantum operations and permits secret sharing for an arbitrary but no less than threshold-value number of classical participants with much lower bandwidth.
Abstract: With prevalent attacks in communication, sharing a secret between communicating parties is an ongoing challenge. Moreover, it is important to integrate quantum solutions with classical secret sharing schemes with low computational cost for the real world use. This paper proposes a novel hybrid threshold adaptable quantum secret sharing scheme, using an m-bonacci orbital angular momentum (OAM) pump, Lagrange interpolation polynomials, and reverse Huffman-Fibonacci-tree coding. To be exact, we employ entangled states prepared by m-bonacci sequences to detect eavesdropping. Meanwhile, we encode m-bonacci sequences in Lagrange interpolation polynomials to generate the shares of a secret with reverse Huffman-Fibonacci-tree coding. The advantages of the proposed scheme is that it can detect eavesdropping without joint quantum operations, and permits secret sharing for an arbitrary but no less than threshold-value number of classical participants with much lower bandwidth. Also, in comparison with existing quantum secret sharing schemes, it still works when there are dynamic changes, such as the unavailability of some quantum channel, the arrival of new participants and the departure of participants. Finally, we provide security analysis of the new hybrid quantum secret sharing scheme and discuss its useful features for modern applications.
812 citations
TL;DR: A therapeutic bacteriophage preparation targeting antibiotic‐resistant Pseudomonas aeruginosa in chronic otitis is evaluated to evaluate the efficacy and safety of this preparation.
Abstract: Objectives: To evaluate the efficacy and safety of a therapeutic bacteriophage preparation (Biophage-PA) targeting antibiotic-resistant Pseudomonas aeruginosa in chronic otitis.
Design: Randomised, double-blind, placebo-controlled Phase I/II clinical trial approved by UK Medicines and Healthcare products Regulatory Agency (MHRA) and the Central Office for Research Ethics Committees (COREC) ethical review process.
Setting: A single specialist university hospital.
Participants: 24 patients with chronic otitis with a duration of several years (2–58). Each patient had, at the time of entry to the trial, an ear infection because of an antibiotic-resistant P. aeruginosa strain sensitive to one or more of the six phages present in Biophage-PA. Participants were randomised in two groups of 12 treated with either a single dose of Biophage-PA or placebo and followed up at 7, 21 and 42 days after treatment by the same otologist. Ears were thoroughly cleaned on each occasion and clinical and microbiological indicators measured.
Main outcome measures: Physician assessed erythema/inflammation, ulceration/granulation/polyps, discharge quantity, discharge type and odour using a Visual Analogue Scale (VAS). Patients reported discomfort, itchiness, wetness and smell also using a VAS. Bacterial levels of P. aeruginosa and phage counts from swabs were measured initially and at follow-up. At each visit patients were asked about side effects using a structured form. Digital otoscopic images were obtained on days 0 and 42 for illustrative purposes only.
Results: Relative to day 0, pooled patient- and physician-reported clinical indicators improved for the phage treated group relative to the placebo group. Variation from baseline levels was statistically significant for combined data from all clinic days only for the phage treated group. Variation from baseline levels was statistically significant for the majority of the patient assessed clinical indicators only for the phage treated group. P. aeruginosa counts were significantly lower only in the phage treated group. No treatment related adverse event was reported.
Conclusion: The first controlled clinical trial of a therapeutic bacteriophage preparation showed efficacy and safety in chronic otitis because of chemo-resistant P. aeruginosa.
724 citations