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Phage and Therapy
Editor(s): HongPing Wei, PhD, Professor Wuhan Institute of Virology, China
This issue of Virologica Sinica is to celebrate the 100th anniversary of the discovery of “fi lterable lytic factor” or “bacteriophage” (1915-2015). During the past 100 years, both basic knowledge and applications of bacteriophages have been substantially explored and developed. In recent years, bacteriophage research is booming and holding the hope to tackle the rise of antimicrobial resistance in the post-antibiotic era. In this issue, new phages are introduced, phage lytic enzymes are described, phage and host interactions are discussed, and successful experiences of phage therapy are shared. The cover illustrates the phages in this issue: ΦVMY22 (golden yellow), ΦCASbig (orange red), ΦKAZ14(magenta). And the phage in blue color is the courtesy of the Core Facility of Wuhan Institute of Virology.
  • Experience of the Eliava Institute in bacteriophage therapy

    Mzia Kutateladze

    2015, 30(1): 80 doi: 10.1007/s12250-014-3557-0

    Published: 05 February 2015
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  • Selection of phages and conditions for the safe phage therapy against Pseudomonas aeruginosa infections

    Victor Krylov, Olga Shaburova, Elena Pleteneva, Sergey Krylov, Alla Kaplan, Maria Burkaltseva, Olga Polygach, Elena Chesnokova

    2015, 30(1): 33 doi: 10.1007/s12250-014-3546-3

    Received: 15 November 2014 Accepted: 30 January 2015 Published: 05 February 2015
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    The emergence of multidrug-resistant bacterial pathogens forced us to consider the phage therapy as one of the possible alternative approaches to treatment. The purpose of this paper is to consider the conditions for the safe, long-term use of phage therapy against various infections caused by Pseudomonas aeruginosa. We describe the selection of the most suitable phages, their most effective combinations and some approaches for the rapid recognition of phages unsuitable for use in therapy. The benefi ts and disadvantages of the various different approaches to the preparation of phage mixtures are considered, together with the specifi c conditions that are required for the safe application of phage therapy in general hospitals and the possibilities for the development of personalized phage therapy.
  • Bacteriophages, revitalized after 100 years in the shadow of antibiotics

    Hongping Wei

    2015, 30(1): 1 doi: 10.1007/s12250-014-3562-y

    Published: 05 February 2015
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    The year 2015 marks 100 years since Dr. Frederick Twort discovered the “filterable lytic factor”, which was later independently discovered and named “bacteriophage” by Dr.Felix d'Herelle. On this memorable centennial, it is exciting to see a special issue published by Virologica Sinica on Phages and Therapy. In this issue, readers will not only find that bacteriophage research is a booming field but also learn about the diverse applications currently being explored for bacteriophages. The biggest driving force behind these applications is the serious threat of bacterial antibiotic resistance that is emerging in the current era
  • Molecular dissection of phage lysin PlySs2: integrity of the catalytic and cell wall binding domains is essential for its broad lytic activity

    Yanling Huang, Hang Yang, Junping Yu, Hongping Wei

    2015, 30(1): 45 doi: 10.1007/s12250-014-3535-6

    Received: 09 November 2014 Accepted: 23 January 2015 Published: 04 February 2015
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    The novel phage lysin PlySs2, is reported to be highly active against various bacteria, including staphylococci, streptococci and Listeria. However, the molecular mechanisms underlying its broad lytic spectrum remain to be established. In the present study, the lytic activity of the catalytic domain (CD, PlySc) and binding specificity of the cell wall binding domain (CBD, PlySb) of PlySs2 were examined. Our results showed that PlySc alone maintains very limited lytic activity. Enhanced green fluorescent protein (EGFP)-fused PlySb displayed high binding affinity to the streptococcal strains tested, including S. suis, S. dysgalactiae, and S. agalactiae, but not staphylococci, supporting its utility as a good CBD donor for streptococcal-targeted lysin engineering. EGFP-fused intact PlySs2 similarly displayed high affinity for streptococci, but not staphylococci. Notably, four truncated PlySb fragments showed no binding capacity. These fi ndings collectively indicate that integrity of the PlySc and PlySb domains is an essential determinant of the broad lytic activity of PlySs2.
  • T4-like coliphage ΦKAZ14 virulent to pathogenic and extended spectrum β-lactamase-producing Escherichia coli of poultry origin

    Kaikabo Adamu Ahmad, Abdulkarim Sabo Mohanmmed, Faridah Abas, Sieo Chin Chin

    2015, 30(1): 73 doi: 10.1007/s12250-014-3541-8

    Published: 03 February 2015
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  • Bacteriophage therapy against Enterobacteriaceae

    Youqiang Xu, Yong Liu, Yang Liu, Jiangsen Pei, Su Yao, Chi Cheng

    2015, 30(1): 11 doi: 10.1007/s12250-014-3543-6

    Received: 13 November 2014 Accepted: 07 January 2015 Published: 03 February 2015
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    The Enterobacteriaceae are a class of gram-negative facultative anaerobic rods, which can cause a variety of diseases, such as bacteremia, septic arthritis, endocarditis, osteomyelitis, lower respiratory tract infections, skin and soft-tissue infections, urinary tract infections, intra-abdominal infections and ophthalmic infections, in humans, poultry, animals and fi sh. Disease caused by Enterobacteriaceae cause the deaths of millions of people every year, resulting in enormous economic loss. Drug treatment is a useful and effi cient way to control Enterobacteriaceae infections. However, with the abuse of antibiotics, drug resistance has been found in growing number of Enterobacteriaceae infections and, as such, there is an urgent need to find new methods of control. Bacteriophage therapy is an efficient alternative to antibiotics as it employs a different antibacterial mechanism. This paper summarizes the history of bacteriophage therapy, its bacterial lytic mechanisms, and the studies that have focused on Enterobacteriaceae and bacteriophage therapy.
  • Isolation and characterization of glacier VMY22, a novel lytic cold-active bacteriophage of Bacillus cereus

    Xiuling Ji, Chunjing Zhang, Yuan Fang, Qi Zhang, Lianbing Lin, Bing Tang, Yunlin Wei

    2015, 30(1): 52 doi: 10.1007/s12250-014-3529-4

    Received: 30 October 2014 Accepted: 21 January 2015 Published: 02 February 2015
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    As a unique ecological system with low temperature and low nutrient levels, glaciers are considered a “living fossil” for the research of evolution. In this work, a lytic cold-active bacteriophage designated VMY22 against Bacillus cereus MYB41-22 was isolated from Mingyong Glacier in China, and its characteristics were studied. Electron microscopy revealed that VMY22 has an icosahedral head (59.2 nm in length, 31.9 nm in width) and a tail (43.2 nm in length). Bacteriophage VMY22 was classifi ed as a Podoviridae with an approximate genome size of 18 to 20 kb. A one-step growth curve revealed that the latent and the burst periods were 70 and 70 min, respectively, with an average burst size of 78 bacteriophage particles per infected cell. The pH and thermal stability of bacteriophage VMY22 were also investigated. The maximum stability of the bacteriophage was observed to be at pH 8.0 and it was comparatively stable at pH 5.0-9.0. As VMY22 is a cold-active bacteriophage with low production temperature, its characterization and the relationship between MYB41-22 and Bacillus cereus bacteriophage deserve further study.
  • Isolation and characterization of a lytic bacteriophage φKp-lyy15 of Klebsiella pneumoniae

    Yinyin Lu, Hongyan Shi, Zhe Zhang, Fang Han, Jinghua Li, Yanbo Sun

    2015, 30(1): 66 doi: 10.1007/s12250-014-3523-x

    Published: 30 January 2015
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  • Isolation and complete genome sequence of a novel virulent mycobacteriophage, CASbig

    Tieshan Teng, Junping Yu, Hang Yang, Hongping Wei

    2015, 30(1): 76 doi: 10.1007/s12250-014-3545-4

    Published: 26 January 2015
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  • Expression and purification of recombinant lyase gp17 from the LSB-1 phage in Escherichia coli

    Taiwu Wang, Hui Lin, Lu Zhang, Guorong Huang, Long Wu, Lei Yu, Hongyan Xiong

    2015, 30(1): 69 doi: 10.1007/s12250-014-3527-6

    Published: 22 January 2015
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  • A novel transposable Mu-like prophage in Bacillus alcalophilus CGMCC 1.3604 (ATCC 27647)

    Junjie Yang, Yimeng Kong, Xuan Li, Sheng Yang

    2015, 30(1): 63 doi: 10.1007/s12250-014-3497-8

    Published: 22 January 2015
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  • Survival and proliferation of the lysogenic bacteriophage CTXΦ in Vibrio cholerae

    Fenxia Fan, Biao Kan

    2015, 30(1): 19 doi: 10.1007/s12250-014-3550-7

    Received: 02 December 2014 Accepted: 12 January 2015 Published: 20 January 2015
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    The lysogenic phage CTXΦ of Vibrio cholerae can transfer the cholera toxin gene both horizontally (inter-strain) and vertically (cell proliferation). Due to its diversity in form and species, the complexity of regulatory mechanisms, and the important role of the infection mechanism in the production of new virulent strains of V. cholerae, the study of the lysogenic phage CTXΦ has attracted much attention. Based on the progress of current research, the genomic features and their arrangement, the host-dependent regulatory mechanisms of CTXΦ phage survival, proliferation and propagation were reviewed to further understand the phage's role in the evolutionary and epidemiological mechanisms of V. cholerae.
  • Bacteriophage secondary infection

    Stephen T Abedon

    2015, 30(1): 3 doi: 10.1007/s12250-014-3547-2

    Received: 17 November 2014 Accepted: 29 December 2014 Published: 13 January 2015
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    Phages are credited with having been fi rst described in what we now, offi cially, are commemorating as the 100th. anniversary of their discovery. Those one-hundred years of phage history have not been lacking in excitement, controversy, and occasional convolution. One such complication is the concept of secondary infection, which can take on multiple forms with myriad consequences. The terms secondary infection and secondary adsorption, for example, can be used almost synonymously to describe virion interaction with already phage-infected bacteria, and which can result in what are described as superinfection exclusion or superinfection immunity. The phrase secondary infection also may be used equivalently to superinfection or coinfection, with each of these terms borrowed from medical microbiology, and can result in genetic exchange between phages, phage-on-phage parasitism, and various partial reductions in phage productivity that have been termed mutual exclusion, partial exclusion, or the depressor effect. Alternatively, and drawing from epidemiology, secondary infection has been used to describe phage population growth as that can occur during active phage therapy as well as upon phage contamination of industrial ferments. Here primary infections represent initial bacterial population exposure to phages while consequent phage replication can lead to additional, that is, secondary infections of what otherwise are not yet phage-infected bacteria. Here I explore the varying meanings and resultant ambiguity that has been associated with the term secondary infection. I suggest in particular that secondary infection, as distinctly different phenomena, can in multiple ways infl uence the success of phage-mediated biocontrol of bacteria, also known as, phage therapy.
  • Variation of resistance and infectivity between Pseudomonas fluorescens SBW25 and bacteriophage Ф2 and its therapeutic implications

    Hanchen Chen, Guohua Chen

    2015, 30(1): 59 doi: 10.1007/s12250-014-3490-2

    Published: 12 January 2015
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