Isolation and Characterization of Bacteriophages Targeting Uropathogenic E. coli

dc.contributor.advisorPassmore, Jo-Ann
dc.contributor.advisorFroissart, Remy
dc.contributor.advisorGamieldien, Hoyam
dc.contributor.authorMagwai, Thandi
dc.date.accessioned2020-02-13T08:40:30Z
dc.date.available2020-02-13T08:40:30Z
dc.date.issued2019
dc.date.updated2020-02-13T08:40:18Z
dc.description.abstractUrinary tract infections (UTI)are one of the most common human bacterial infections, caused by uropathogenic E. coli (UPEC). Conventionally, UTI’s are treated with antibiotics, such as sulpha-mathoxazole/trimethoprim and ampicillin. However, a significant proportion of UPEC strains have become resistant to these antibiotics, resulting in a significant burden on the health care system worldwide. Bacteriophages (phages) that target E. coli strains could provide an alternative treatment for UTIs, particularly those resistant to antibiotics. This study aimed to screen a variety of environmental samples for phages that target a UPEC strains and characterize these phenotypically and genotypically, towards the development of a candidate phage preparation for treatment for antibiotic-resistant UPEC. Environmental samples (including faeces cattle, sheep, horse, goat faeces, river water, raw cow milk and mud) were collected from various sources around the City of Cape Town and screened for phages using an E. coli laboratory strain; K-12 MG1655. Lytic phages against E. coli MG1655 were purified and host-range testing was conducted against a panel of 11 UPEC strains form the E. coli reference collection (ECOR). These lytic phages were characterized phenotypically using transmission electron microscopy (TEM) using negative staining and genotypically using restriction enzyme HaeIII. In total, 41 phages that were lytic against MG1655 were isolated from six different environmental samples. Of these, 31/41 (76%) were lytic against 7/11 (64%) UPEC strains tested. Four phages (16-3, 16-4, 16-5 and 16-7; all isolated from raw milk) had the broadest host range of all the phages screened, being lyticagainst4/11(36%) UPEC strains. UPEC strain ECOR-40 was the most susceptible of the E. coli strains tested, being susceptible to 18/31 (58%) of the lytic phages isolated. In contrast, four UPEC strains (including ECOR-14, -60, -62 and -64) were not susceptible to any of the phages isolated. Ninety percent (28/31) of the isolated phages were structurally similar to four known phage families; including Myoviridae, Siphoviridae, Inoviridae and Rudiviridae. The remaining 10% (3/31) had structures that did not resemble any ofthe known phage families. DNA was x isolated from all 31 phage isolates to screen for similarities in restriction patterns of isolates. Of these, RFLP banding was clear for 5/31 samples; which showed that 5/5 phages were unique based on their banding patterns. In conclusion, this study demonstrated the existence of several unique E. coli phages in nature and their ability to target several of the UPEC strains known to cause UTI. Although time did not allow for sequencing of the full genomes of those isolates with unique characteristics in this study, this should be a priority for this research going forward.
dc.identifier.apacitationMagwai, T. (2019). <i>Isolation and Characterization of Bacteriophages Targeting Uropathogenic E. coli</i>. (). ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences. Retrieved from http://hdl.handle.net/11427/31065en_ZA
dc.identifier.chicagocitationMagwai, Thandi. <i>"Isolation and Characterization of Bacteriophages Targeting Uropathogenic E. coli."</i> ., ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2019. http://hdl.handle.net/11427/31065en_ZA
dc.identifier.citationMagwai, T. 2019. Isolation and Characterization of Bacteriophages Targeting Uropathogenic E. coli.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Magwai, Thandi AB - Urinary tract infections (UTI)are one of the most common human bacterial infections, caused by uropathogenic E. coli (UPEC). Conventionally, UTI’s are treated with antibiotics, such as sulpha-mathoxazole/trimethoprim and ampicillin. However, a significant proportion of UPEC strains have become resistant to these antibiotics, resulting in a significant burden on the health care system worldwide. Bacteriophages (phages) that target E. coli strains could provide an alternative treatment for UTIs, particularly those resistant to antibiotics. This study aimed to screen a variety of environmental samples for phages that target a UPEC strains and characterize these phenotypically and genotypically, towards the development of a candidate phage preparation for treatment for antibiotic-resistant UPEC. Environmental samples (including faeces cattle, sheep, horse, goat faeces, river water, raw cow milk and mud) were collected from various sources around the City of Cape Town and screened for phages using an E. coli laboratory strain; K-12 MG1655. Lytic phages against E. coli MG1655 were purified and host-range testing was conducted against a panel of 11 UPEC strains form the E. coli reference collection (ECOR). These lytic phages were characterized phenotypically using transmission electron microscopy (TEM) using negative staining and genotypically using restriction enzyme HaeIII. In total, 41 phages that were lytic against MG1655 were isolated from six different environmental samples. Of these, 31/41 (76%) were lytic against 7/11 (64%) UPEC strains tested. Four phages (16-3, 16-4, 16-5 and 16-7; all isolated from raw milk) had the broadest host range of all the phages screened, being lyticagainst4/11(36%) UPEC strains. UPEC strain ECOR-40 was the most susceptible of the E. coli strains tested, being susceptible to 18/31 (58%) of the lytic phages isolated. In contrast, four UPEC strains (including ECOR-14, -60, -62 and -64) were not susceptible to any of the phages isolated. Ninety percent (28/31) of the isolated phages were structurally similar to four known phage families; including Myoviridae, Siphoviridae, Inoviridae and Rudiviridae. The remaining 10% (3/31) had structures that did not resemble any ofthe known phage families. DNA was x isolated from all 31 phage isolates to screen for similarities in restriction patterns of isolates. Of these, RFLP banding was clear for 5/31 samples; which showed that 5/5 phages were unique based on their banding patterns. In conclusion, this study demonstrated the existence of several unique E. coli phages in nature and their ability to target several of the UPEC strains known to cause UTI. Although time did not allow for sequencing of the full genomes of those isolates with unique characteristics in this study, this should be a priority for this research going forward. DA - 2019 DB - OpenUCT DP - University of Cape Town KW - Medicine LK - https://open.uct.ac.za PY - 2019 T1 - Isolation and Characterization of Bacteriophages Targeting Uropathogenic E. coli TI - Isolation and Characterization of Bacteriophages Targeting Uropathogenic E. coli UR - http://hdl.handle.net/11427/31065 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/31065
dc.identifier.vancouvercitationMagwai T. Isolation and Characterization of Bacteriophages Targeting Uropathogenic E. coli. []. ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2019 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/31065en_ZA
dc.language.rfc3066eng
dc.publisher.departmentDepartment of Clinical Laboratory Sciences
dc.publisher.facultyFaculty of Health Sciences
dc.subjectMedicine
dc.titleIsolation and Characterization of Bacteriophages Targeting Uropathogenic E. coli
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMSc
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