TY - JOUR
T1 - Fighting fire with fire
T2 - Phage potential for the treatment of E. coli o157 infection
AU - Howard-Varona, Cristina
AU - Vik, Dean R.
AU - Solonenko, Natalie E.
AU - Li, Yueh Fen
AU - Gazitua, M. Consuelo
AU - Chittick, Lauren
AU - Samiec, Jennifer K.
AU - Jensen, Aubrey E.
AU - Anderson, Paige
AU - Howard-Varona, Adrian
AU - Kinkhabwala, Anika A.
AU - Abedon, Stephen T.
AU - Sullivan, Matthew B.
N1 - Funding Information:
Funding: Research reported in this publication was partly supported by the Infectious Diseases Institute Seed Grant program through Ohio State University (OSU) to M.B.S., an National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) award # 1-T32-AI-112542 to C.H.-V. through the Infectious Disease Institute at OSU, as well as the Bill and Melinda Gates Foundation Grand Challenges Award OPP1139917 to Epibiome.
Funding Information:
Research reported in this publication was partly supported by the Infectious Diseases Institute Seed Grant program through Ohio State University (OSU) to M.B.S., an National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) award # 1-T32-AI-112542 to C.H.-V. through the Infectious Disease Institute at OSU, as well as the Bill and Melinda Gates Foundation Grand Challenges Award OPP1139917 to Epibiome. Acknowledgments: We thank Michelle Davison and Rebecca Lu at Epibiome for DNA extraction and sequencing, respectively, as well as Zachary Hobbs and Ryan Honaker from Epibiome for providing the phages. We also thank the following undergraduates for their help with initial phage–host optimizations: Alice L. Herneisen, Catherine E. Johnson, John M. Thomas, and Storm A. Mohn. We also thank OSU PhD rotation students Siavash Azari, Sravya Kovvali, and Yiwei Liu.
Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2018/12
Y1 - 2018/12
N2 - Hemolytic–uremic syndrome is a life-threating disease most often associated with Shiga toxin-producing microorganisms like Escherichia coli (STEC), including E. coli O157:H7. Shiga toxin is encoded by resident prophages present within this bacterium, and both its production and release depend on the induction of Shiga toxin-encoding prophages. Consequently, treatment of STEC infections tend to be largely supportive rather than antibacterial, in part due to concerns about exacerbating such prophage induction. Here we explore STEC O157:H7 prophage induction in vitro as it pertains to phage therapy—the application of bacteriophages as antibacterial agents to treat bacterial infections—to curtail prophage induction events, while also reducing STEC O157:H7 presence. We observed that cultures treated with strictly lytic phages, despite being lysed, produce substantially fewer Shiga toxin-encoding temperate-phage virions than untreated STEC controls. We therefore suggest that phage therapy could have utility as a prophylactic treatment of individuals suspected of having been recently exposed to STEC, especially if prophage induction and by extension Shiga toxin production is not exacerbated.
AB - Hemolytic–uremic syndrome is a life-threating disease most often associated with Shiga toxin-producing microorganisms like Escherichia coli (STEC), including E. coli O157:H7. Shiga toxin is encoded by resident prophages present within this bacterium, and both its production and release depend on the induction of Shiga toxin-encoding prophages. Consequently, treatment of STEC infections tend to be largely supportive rather than antibacterial, in part due to concerns about exacerbating such prophage induction. Here we explore STEC O157:H7 prophage induction in vitro as it pertains to phage therapy—the application of bacteriophages as antibacterial agents to treat bacterial infections—to curtail prophage induction events, while also reducing STEC O157:H7 presence. We observed that cultures treated with strictly lytic phages, despite being lysed, produce substantially fewer Shiga toxin-encoding temperate-phage virions than untreated STEC controls. We therefore suggest that phage therapy could have utility as a prophylactic treatment of individuals suspected of having been recently exposed to STEC, especially if prophage induction and by extension Shiga toxin production is not exacerbated.
KW - Antibiotic-resistant bacteria
KW - Bacteriophage therapy
KW - Lysogenic conversion
KW - Phage therapy
KW - Prophage induction
KW - Read recruitment
KW - Shiga toxin
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UR - http://www.scopus.com/inward/citedby.url?scp=85057190200&partnerID=8YFLogxK
U2 - 10.3390/antibiotics7040101
DO - 10.3390/antibiotics7040101
M3 - Article
AN - SCOPUS:85057190200
VL - 7
JO - Antibiotics
JF - Antibiotics
SN - 2079-6382
IS - 4
M1 - 101
ER -