Intranasal Treatment with Bacteriophage Rescues Mice from
            <i>Acinetobacter Baumannii</i>
            -Mediated Pneumonia

Wang, Yong; Mi, Zhiqiang; Niu, Wenkai; An, Xiaoping; Yuan, Xin; Liu, Huiying; Li, Puyuan; Liu, Yannan; Feng, Yongjun; Huang, Yong; Zhang, Xianglilan; Zhang, Zhiyi; Fan, Hang; Peng, Fan; Tong, Yigang; Bai, Chunmei

doi:10.2217/fmb.16.11

Cited by 46 publications

(32 citation statements)

References 20 publications

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“…Several rodent studies have suggested that strain-specific phages can improve outcomes from intranasally inoculated lung infection, intraperitoneal sepsis, or wound infections (288,(292)(293)(294). Lysin peptides from phages have also been studied as effective treatments for A. baumannii infections in mice (295,296).…”

Section: Bacteriophagesmentioning

confidence: 99%

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

et al. 2017

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SUMMARY Acinetobacter is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by Acinetobacter spp. are increasingly reported. Transmission of Acinetobacter and subsequent disease is facilitated by the organism's environmental tenacity, resistance to desiccation, and evasion of host immunity. The virulence properties demonstrated by Acinetobacter spp. primarily stem from evasion of rapid clearance by the innate immune system, effectively enabling high bacterial density that triggers lipopolysaccharide (LPS)–Toll-like receptor 4 (TLR4)-mediated sepsis. Capsular polysaccharide is a critical virulence factor that enables immune evasion, while LPS triggers septic shock. However, the primary driver of clinical outcome is antibiotic resistance. Administration of initially effective therapy is key to improving survival, reducing 30-day mortality threefold. Regrettably, due to the high frequency of this organism having an extreme drug resistance (XDR) phenotype, early initiation of effective therapy is a major clinical challenge. Given its high rate of antibiotic resistance and abysmal outcomes (up to 70% mortality rate from infections caused by XDR strains in some case series), new preventative and therapeutic options for Acinetobacter spp. are desperately needed.

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Section: Bacteriophagesmentioning

confidence: 99%

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

et al. 2017

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“…Inhalation with phages had a life‐saving effect in hemorrhagic pneumonia caused by Pseudomonas aeruginosa in a mink model, Acinetobacter baumannii ‐ or Klebsiella pneumoniae ‐induced pneumonia in mice, and fatal E. coli respiratory infection in chickens . Experimental pneumonia in mice was reduced by phage therapy in a time‐ and dose‐dependent manner . Very effective clearance of respiratory tract infecting bacteria was visualized by the group of Debarbieux …”

Section: Entering the Systemmentioning

confidence: 99%

“…100 Experimental pneumonia in mice was reduced by phage therapy in a time-and dose-dependent manner. 101 Very effective clearance of respiratory tract infecting bacteria was visualized by the group of Debarbieux. 102,103…”

Section: Respiratory Tractmentioning

confidence: 99%

Phage therapy: What factors shape phage pharmacokinetics and bioavailability? Systematic and critical review

Dąbrowska

2019

Medicinal Research Reviews

199

204

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Bacteriophages are not forgotten viruses anymore: scientists and practitioners seek to understand phage pharmacokinetics in animals and humans, investigating bacteriophages as therapeutics, nanocarriers or microbiome components. This review provides a comprehensive overview of factors that determine phage circulation, penetration, and clearance, and that in consequence determine phage applicability for medicine. It makes use of experimental data collected by the phage community so far (PubMed 1924‐2016, including non‐English reports), combining elements of critical and systematic review. This study covers phage ability to enter a system by various routes of administration, how (and if) the phage may access various tissues and organs, and finally what mechanisms determine the courses of phage clearance. The systematic review method was applied to analyze (i) phage survival in the gut (gut transit) and (ii) phage ability to enter the mammalian system by many administration routes. Aspects that have not yet been covered by a sufficient number of reports for mathematical analysis, as well as mechanisms underlying trends, are discussed in the form of a critical review. In spite of the extraordinary diversity of bacteriophages and possible phage applications, the analysis revealed that phage morphology, phage specificity, phage dose, presence of sensitive bacteria or the characteristics of treated individuals (age, taxonomy) may affect phage bioavailability in animals and humans. However, once phages successfully enter the body, they reach most organs, including the central nervous system. Bacteriophages are cleared mainly by the immune system: innate immunity removes phages even when no specific response to bacteriophages has yet developed.

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“…Mice with artificial burns, pneumonia, pulmonary infections with various microbes ( Pseudomonas spp., Staphylococcuss spp., Enterococcuss spp., Klebsiella pneumoniae, Escherichia coli ) were successfully treated with phages ( Biswas et al, 2002 ; Chibani-Chennoufi et al, 2004 ; Vinodkumar et al, 2005 ; McVay et al, 2007 ; Debarbieux et al, 2010 ; Morello et al, 2011 ). Although several A. baumannii phages have been isolated and characterized in terms of potential therapeutic application ( Soothill, 1992 ; Yang et al, 2010 ; Popova et al, 2012 ), a very few in vivo trials for A. baumannii phages have been reported: Wang et al (2016) , showed successfully use of phage intranasal application for treatment pneumonia on mice model. All mice survived after intranasal application of phages published by Jeon et al (2016) as well.…”

Section: Introductionmentioning

confidence: 99%

Characterization and Testing the Efficiency of Acinetobacter baumannii Phage vB-GEC_Ab-M-G7 as an Antibacterial Agent

et al. 2016

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Acinetobacter baumannii is a gram-negative, non-motile bacterium that, due to its multidrug resistance, has become a major nosocomial pathogen. The increasing number of multidrug resistant (MDR) strains has renewed interest in phage therapy. The aim of our study was to assess the effectiveness of phage administration in Acinetobacter baumannii wound infections in an animal model to demonstrate phage therapy as non-toxic, safe and alternative antibacterial remedy. Using classical methods for the study of bacteriophage properties, we characterized phage vB-GEC_Ab-M-G7 as a dsDNA myovirus with a 90 kb genome size. Important characteristics of vB-GEC_Ab-M-G7include a short latent period and large burst size, wide host range, resistance to chloroform and thermal and pH stability. In a rat wound model, phage application effectively decreased the number of bacteria isolated from the wounds of successfully treated animals. This study highlights the effectiveness of the phage therapy and provides further insight into treating infections caused by MDR strains using phage administration.

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Intranasal Treatment with Bacteriophage Rescues Mice from Acinetobacter Baumannii -Mediated Pneumonia

Abstract: This research demonstrates that intranasal application of bacteriophage is viable, and could provide complete protection from pneumonia caused by A. baumannii.

Cited by 46 publications

References 20 publications

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

Phage therapy: What factors shape phage pharmacokinetics and bioavailability? Systematic and critical review

Characterization and Testing the Efficiency of Acinetobacter baumannii Phage vB-GEC_Ab-M-G7 as an Antibacterial Agent

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