First‐in‐human application of double‐stranded RNA bacteriophage in the treatment of pulmonary <i>Pseudomonas aeruginosa</i> infection

Li, Linlin; Zhong, Qian; Zhao, Yunze; Bao, Juan Francisco Gibaja; Liu, Bing; Zhong, Zhuojun; Wang, Jing; Yang, Lan; Zhang, Tingting; Cheng, Mengjun; Wu, Nannan; Zhu, Tongyu; Le, Shuai

doi:10.1111/1751-7915.14217

Cited by 11 publications

(7 citation statements)

References 23 publications

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“…These are all as found in situ while treating infections caused by what are typically somewhat uncharacterized bacterial strains and, in many cases, also in combination with antibiotics [ 41 , 57 , 86 , 87 , 88 , 89 ], which can have antagonistic impacts on phage infection abilities [ 41 , 51 , 85 , 90 ]. In particular for the latter, note that of 18 clinical phage therapy studies that I was able to obtain—published in 2023 or, at the time of writing, which are published but still online ahead of print—at least 16 indicate treatments using phages in combination with antibiotics [ 57 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 ]. See also [ 109 ], where 79 of the 114 clinical phage treatments reported “were administered in combination with standard-of-care antibiotics”.…”

Section: Discussionmentioning

confidence: 99%

Automating Predictive Phage Therapy Pharmacology

Abedon

2023

Antibiotics

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Viruses that infect as well as often kill bacteria are called bacteriophages, or phages. Because of their ability to act bactericidally, phages increasingly are being employed clinically as antibacterial agents, an infection-fighting strategy that has been in practice now for over one hundred years. As with antibacterial agents generally, the development as well as practice of this phage therapy can be aided via the application of various quantitative frameworks. Therefore, reviewed here are considerations of phage multiplicity of infection, bacterial likelihood of becoming adsorbed as a function of phage titers, bacterial susceptibility to phages also as a function of phage titers, and the use of Poisson distributions to predict phage impacts on bacteria. Considered in addition is the use of simulations that can take into account both phage and bacterial replication. These various approaches can be automated, i.e., by employing a number of online-available apps provided by the author, the use of which this review emphasizes. In short, the practice of phage therapy can be aided by various mathematical approaches whose implementation can be eased via online automation.

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Section: Discussionmentioning

confidence: 99%

Automating Predictive Phage Therapy Pharmacology

Abedon

2023

Antibiotics

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“…To date, most phage therapy candidates have been assessed against P. aeruginosa , with a mixture of clinical trials [ 163 , 165 ], single compassionate-use cases [ 167 , 168 , 169 , 170 ], and in vitro model studies [ 171 , 172 , 173 , 174 ]. The single completed phase I/II clinical trial included chronic otitis media patients and found phage therapy yielded the best clinical outcomes against antibiotic resistant P. aeruginosa infections, significantly lowered bacterial loads, and did not elicit adverse events [ 163 ].…”

Section: Emerging Therapeutic Approachesmentioning

confidence: 99%

“…The single completed phase I/II clinical trial included chronic otitis media patients and found phage therapy yielded the best clinical outcomes against antibiotic resistant P. aeruginosa infections, significantly lowered bacterial loads, and did not elicit adverse events [ 163 ]. In the cases of compassionate use, all reported either clinical improvement [ 167 , 169 ] or complete eradication [ 168 , 170 ] after phage therapy. Of note, in the two cases with complete eradication, phage therapy was combined with antibiotics or immunoglobulin therapy, highlighting phage therapy’s potential for synergistic effects.…”

Section: Emerging Therapeutic Approachesmentioning

confidence: 99%

The Respiratory Microbiome in Paediatric Chronic Wet Cough: What Is Known and Future Directions

Atto,

Anteneh,

Bialasiewicz

et al. 2023

JCM

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Chronic wet cough for longer than 4 weeks is a hallmark of chronic suppurative lung diseases (CSLD), including protracted bacterial bronchitis (PBB), and bronchiectasis in children. Severe lower respiratory infection early in life is a major risk factor of PBB and paediatric bronchiectasis. In these conditions, failure to clear an underlying endobronchial infection is hypothesised to drive ongoing inflammation and progressive tissue damage that culminates in irreversible bronchiectasis. Historically, the microbiology of paediatric chronic wet cough has been defined by culture-based studies focused on the detection and eradication of specific bacterial pathogens. Various ‘omics technologies now allow for a more nuanced investigation of respiratory pathobiology and are enabling development of endotype-based models of care. Recent years have seen substantial advances in defining respiratory endotypes among adults with CSLD; however, less is understood about diseases affecting children. In this review, we explore the current understanding of the airway microbiome among children with chronic wet cough related to the PBB–bronchiectasis diagnostic continuum. We explore concepts emerging from the gut–lung axis and multi-omic studies that are expected to influence PBB and bronchiectasis endotyping efforts. We also consider how our evolving understanding of the airway microbiome is translating to new approaches in chronic wet cough diagnostics and treatments.

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“…For instance, the degradation of bacterial cell wall by dsRNA phage lytic enzyme [143] or inhibition of cell wall synthesis using single-gene lysis (Slg) protein from ssDNA and ssRNA phages [141,142,144]. (2) Phage cocktail employing natural ssDNA and RNA phages as antimicrobial therapeutics against AMR bacteria and phage-resistant mutants [145,146]. (3) Engineering ssDNA and RNA phages for antibacterial therapies.…”

Section: Phage-derived Lytic Enzymes As Antibacterial Agentsmentioning

confidence: 99%

RNA and Single-Stranded DNA Phages: Unveiling the Promise from the Underexplored World of Viruses

Nguyen,

Watanabe,

Sharmin

et al. 2023

IJMS

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RNA and single-stranded DNA (ssDNA) phages make up an understudied subset of bacteriophages that have been rapidly expanding in the last decade thanks to advancements in metaviromics. Since their discovery, applications of genetic engineering to ssDNA and RNA phages have revealed their immense potential for diverse applications in healthcare and biotechnology. In this review, we explore the past and present applications of this underexplored group of phages, particularly their current usage as therapeutic agents against multidrug-resistant bacteria. We also discuss engineering techniques such as recombinant expression, CRISPR/Cas-based genome editing, and synthetic rebooting of phage-like particles for their role in tailoring phages for disease treatment, imaging, biomaterial development, and delivery systems. Recent breakthroughs in RNA phage engineering techniques are especially highlighted. We conclude with a perspective on challenges and future prospects, emphasizing the untapped diversity of ssDNA and RNA phages and their potential to revolutionize biotechnology and medicine.

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First‐in‐human application of double‐stranded RNA bacteriophage in the treatment of pulmonary Pseudomonas aeruginosa infection

Cited by 11 publications

References 23 publications

Automating Predictive Phage Therapy Pharmacology

Automating Predictive Phage Therapy Pharmacology

The Respiratory Microbiome in Paediatric Chronic Wet Cough: What Is Known and Future Directions

RNA and Single-Stranded DNA Phages: Unveiling the Promise from the Underexplored World of Viruses

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