Restoring logic and data to phage-cures for infectious disease

Philip Serwer; Philip Serwer

doi:10.3934/microbiol.2017.4.706

AIMS Microbiology

2017, Volume 3, Issue 4: 706-712. doi: 10.3934/microbiol.2017.4.706

Previous Article Next Article

Mini review Topical Sections

Restoring logic and data to phage-cures for infectious disease

Philip Serwer ^,

Department of Biochemistry and Structural Biology, The University of Texas Health Center, 7703 Floyd Curl Drive, San Antonio, Texas 28229-3900, USA

Received: 12 June 2017 Accepted: 10 August 2017 Published: 15 August 2017

Antibiotic therapy for infectious disease is being compromised by emergence of multi-drug-resistant bacterial strains, often called superbugs. A response is to use a cocktail of several bacteria-infecting viruses (bacteriophages or phages) to supplement antibiotic therapy. Use of such cocktails is called phage therapy, which has the advantage of response to bacterial resistance that is rapid and not exhaustible. A procedure of well-established success is to make cocktails from stockpiles of stored environmental phages. New phages are added to stockpiles when phage therapy becomes thwarted. The scientific subtext includes optimizing the following aspects: (1) procedure for rapidly detecting, purifying, storing and characterizing phages for optimization of phage cocktails, (2) use of directed evolution in the presence of bacteriostatic compounds to obtain phages that can be most efficiently used for therapy in the presence of these compounds, (3) phage genome sequencing technology and informatics to improve the characterization of phages, and (4) database technology to make optimal use of all relevant information and to rapidly retrieve phages for cocktails that will vary with the infection(s) involved. The use of phage stockpiles has an established record, including a recent major human-therapy success by the US Navy. However, I conclude that most research is not along this track and, therefore, is not likely to lead to real world success. I find that a strong case exists for action to rectify this situation.
- phage characterization,
- phage propagation,
- phage stockpile,
- superbug
Citation: Philip Serwer. Restoring logic and data to phage-cures for infectious disease[J]. AIMS Microbiology, 2017, 3(4): 706-712. doi: 10.3934/microbiol.2017.4.706

Related Papers:

Abstract

Antibiotic therapy for infectious disease is being compromised by emergence of multi-drug-resistant bacterial strains, often called superbugs. A response is to use a cocktail of several bacteria-infecting viruses (bacteriophages or phages) to supplement antibiotic therapy. Use of such cocktails is called phage therapy, which has the advantage of response to bacterial resistance that is rapid and not exhaustible. A procedure of well-established success is to make cocktails from stockpiles of stored environmental phages. New phages are added to stockpiles when phage therapy becomes thwarted. The scientific subtext includes optimizing the following aspects: (1) procedure for rapidly detecting, purifying, storing and characterizing phages for optimization of phage cocktails, (2) use of directed evolution in the presence of bacteriostatic compounds to obtain phages that can be most efficiently used for therapy in the presence of these compounds, (3) phage genome sequencing technology and informatics to improve the characterization of phages, and (4) database technology to make optimal use of all relevant information and to rapidly retrieve phages for cocktails that will vary with the infection(s) involved. The use of phage stockpiles has an established record, including a recent major human-therapy success by the US Navy. However, I conclude that most research is not along this track and, therefore, is not likely to lead to real world success. I find that a strong case exists for action to rectify this situation.

References

[1]	Collignon P (2013) Superbugs in food: a severe public health concern. Lancet Infect Dis 13: 641–643. doi: 10.1016/S1473-3099(13)70141-5
[2]	Xue K (2014) Superbug: an epidemic begins. Harvard Magazine: 40–49.
[3]	Richmond R (2014) Superbug crisis-are animals putting us at risk? Aust Vet J 92: N16.
[4]	Roach DR, Debarbieux L (2017) Phage therapy: awakening a sleeping giant. Emerg Top Life Sci 1: 93–103. doi: 10.1042/ETLS20170002
[5]	Temple KM, Strategies for superbugs: Antibiotic stewardship for rural hospitals. The Rural Monitor, 2017. Available from: https://www.ruralhealthinfo.org/rural-monitor/antibiotic-stewardship/.
[6]	Wenzel RP (2004) The antibiotic pipeline-challenges, costs, and values. N Eng J Med 351: 523–526. doi: 10.1056/NEJMp048093
[7]	Gupta KG, Nayak RP (2014) Dry antibiotic pipeline: Regulatory bottlenecks and regulatory reforms. J Pharmacol Pharmacother 5: 4–7. doi: 10.4103/0976-500X.124405
[8]	Luepke KH, Mohr JF III (2017) The antibiotic pipeline: reviving research and development and speeding drugs to market. Expert Rev Anti-Infect Ther 15: 425–433. doi: 10.1080/14787210.2017.1308251
[9]	Centers for Disease Control and Prevention, Atlanta, GA: US Department of Health and Human Services, Antibiotic resistance threats in the United States, 2013. Available from: https://www.cdc.gov/drugresistance/.
[10]	Summers WC (2001) Bacteriophage therapy. Annu Rev Microbiol 55: 437–451. doi: 10.1146/annurev.micro.55.1.437
[11]	Sulakvelidze A, Alavidze Z, Morris JG (2001) Bacteriophage therapy. Antimicrob Agents Chemother 45: 649–659. doi: 10.1128/AAC.45.3.649-659.2001
[12]	Letarov AV, Golomidova AK, Tarasyan KK (2010) Ecological basis of rational phage therapy. Acta Naturae 2: 60–71.
[13]	Kutter E, De VD, Gvasalia G, et al. (2010) Phage therapy in clinical practice: treatment of human infections. Curr Pharm Biotechnol 11: 69–86. doi: 10.2174/138920110790725401
[14]	Serwer P, Wright ET, Chang JT, et al. (2014) Enhancing and initiating phage-based therapies. Bacteriophage 4: e961869. doi: 10.4161/21597073.2014.961869
[15]	Doss J, Culbertson K, Hahn D, et al. (2017) A review of phage therapy against bacterial pathogens of aquatic and terrestrial organisms. Viruses 9: 50. doi: 10.3390/v9030050
[16]	Kutateladze M (2015) Experience of the Eliava Institute in bacteriophage therapy. Virol Sin 30: 80–81. doi: 10.1007/s12250-014-3557-0
[17]	Sankar A, Merril CR, Biswas B (2014) Therapeutic and prophylactic applications of bacteriophage components in modern medicine. Cold Spring Harb Perspect Med 4: a012518. doi: 10.1101/cshperspect.a012518
[18]	Keller PM, Weber MH (2014) Rational therapy of Clostridium difficile infections. Viszeralmedizin 30: 304–309.
[19]	Weber L, Sewage Saved This Man's Life. Someday It Could Save Yours. Bacteriophages-viruses found in soil, water and human waste-may be the cure in a post-antibiotic world. HuffPost, US Edition, 2017. Available from: http://www.huffingtonpost.com/entry/antibiotic-resistant-superbugs-phage-therapy_us_5913414de4b05e1ca203f7d4.
[20]	Regeimbal JM, Jacobs AC, Corey BW, et al. (2016) Personalized therapeutic cocktail of wild environmental phages rescues mice from Acinetobacter baumannii wound infections. Antimicrob Agents Chemother 60: 5806–5816. doi: 10.1128/AAC.02877-15
[21]	Gross EL, Beall CJ, Kutsch SR, et al. (2012) Beyond Streptococcus mutans: Dental caries onset linked to multiple species by 16S rRNA community analysis. PLoS One 7: e47722. doi: 10.1371/journal.pone.0047722
[22]	Desranleau JM (1949) Progress in the treatment of typhoid fever with Vi bacteriophages. Can J Public Health 40: 473–478.
[23]	Knouf EG, Ward WE, Reichle PA, et al. (1946) Treatment of typhoid fever with type specific bacteriophage. J Amer Med Assoc 132: 134–138. doi: 10.1001/jama.1946.02870380016006
[24]	Serwer P, Hayes SJ, Thomas JA, et al. (2007) Propagating the missing bacteriophages: a large bacteriophage in a new class. Virol J 4: 21. doi: 10.1186/1743-422X-4-21
[25]	Hendrix RW (2009) Jumbo bacteriophages. Curr Top Immunol 328: 229–240.
[26]	Serwer P, Hayes SJ, Zaman S, et al. (2004) Improved isolation of undersampled bacteriophages: finding of distant terminase genes. Virology 329: 412–424. doi: 10.1016/j.virol.2004.08.021
[27]	Serwer P, Hayes SJ, Thomas JA, et al. (2009) Isolation of large and aggregating bacteriophages, In: Clokie MRJ, Kropinski AM, Editors, Bacteriophages: Methods and Protocols, Isolation, Characterization and Interactions, Dordrecht, Netherlands: Springer Science Business Media, 55–66.
[28]	Abedon ST (2016) Bacteriophage exploitation of bacterial biofilms: phage preference for less mature targets? FEMS Microbiol Lett 363: fnv246. doi: 10.1093/femsle/fnv246
[29]	Serwer P, Wright ET (2016) Testing a proposed paradigm shift in analysis of phage DNA packaging. Bacteriophage 6: e1268664. doi: 10.1080/21597081.2016.1268664
[30]	Hardies SC, Thomas JA, Serwer P (2007) Comparative genomics of Bacillus thuringiensis phage 0305φ8-36: defining patterns of descent in a novel ancient phage lineage. Virol J 4: 97. doi: 10.1186/1743-422X-4-97
[31]	Yuan Y, Gao M (2017) Jumbo bacteriophages: An overview. Front Microbiol 8: 403.
[32]	Pathria S, Rolando M, Lieman K, et al. (2012) Islands of non-essential genes, including a DNA translocation operon, in the genome of bacteriophage 0305ϕ8-36. Bacteriophage 2: 25–35. doi: 10.4161/bact.19546
[33]	Dubos R (1986) Louie Pasteur, Free Lance of Science, New York: Da Capo Press, Inc.
[34]	Summers WC (1999) Félix d`Herelle and the Origins of Molecular Biology , 1 Eds., New Haven: Yale University Press.
[35]	Gladstone EG, Molineux IJ, Bull L (2012) Evolutionary principles and synthetic biology: avoiding a molecular tragedy of the commons with an engineered phage. J Biol Eng 6: 13. doi: 10.1186/1754-1611-6-13
[36]	Rose DW (2016) Friends and Partners: The Legacy of Franklin D. Roosevelt and Basil O'Connor in the History of Polio, 1 Eds., London Academic Press.

Reader Comments

Your name:*

Email:*
© 2017 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)