Molecular characterization of twelve predominant Streptococcus pneumoniae serotypes causing invasive infections in Canada from 2011 to 2015

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dc.contributor.authorGolden, Alyssa Rose
dc.contributor.examiningcommitteeMulvey, Michael (Medical Microbiology and Infectious Diseases) Gilmour, Matthew (Medical Microbiology and Infectious Diseases) Graham, Morag (Medical Microbiology and Infectious Diseases) Chiu, Aaron (Pediatrics and Child Health) Bettinger, Julie (University of British Columbia)en_US
dc.contributor.supervisorZhanel, George G (Medical Microbiology and Infectious Diseases) Adam, Heather J (Medical Microbiology and Infectious Diseases)en_US
dc.date.accessioned2018-02-07T16:11:24Z
dc.date.available2018-02-07T16:11:24Z
dc.date.issued2015en_US
dc.date.issued2016en_US
dc.degree.disciplineMedical Microbiology and Infectious Diseasesen_US
dc.degree.levelDoctor of Philosophy (Ph.D.)en_US
dc.description.abstractStreptococcus pneumoniae (SPN) is a diverse and commonly antimicrobial-resistant organism capable of causing invasive disease. The purpose of this thesis was to characterize twelve predominant serotypes of SPN causing invasive infections in Canada from 2011-2015. These serotypes included 3, 6C, 7F, 8, 9N, 11A, 12F, 15A, 19A, 22F, 33F and 35B. We hypothesized that these serotypes would frequently be antimicrobial resistant and/or multidrug resistant (MDR), genetically similar within the serotype and virulent due to the presence of pilus genes. Invasive SPN isolates were obtained from the SAVE study through a partnership between the Canadian Antimicrobial Resistance Alliance and the National Microbiology Laboratory. All strains were tested for antimicrobial susceptibilities and pilus presence. A subset of the above-listed serotypes were characterized using PFGE, MLST and WGS. WGS analyses included phylogeny, recombination prediction and gene extraction. Capsular switch variants were identified using a penicillin-binding protein typing scheme. The hypotheses of this study were closely linked based on the serotype in question. Serotypes 6C, 15A, 19A and 33F were highly diverse, demonstrating numerous sequence types within the serotype and significant amounts of predicted recombination. These four serotypes accounted for most of the MDR SPN identified in this thesis; in contrast, serotypes 7F and 22F were clonal and uncommonly resistant to antimicrobials. The presence of pilus genes was also associated with clonal type, but variably associated with MDR and virulence. PI-1 was identified in a subset of serotype 6C and in antimicrobial susceptible 15A isolates. PI-2 genes were present in all serotype 7F and two-thirds of 11A isolates. The dual genotype was only present in extensively-drug resistant serotype 19A. Recombination had a significant impact on the diversity of the Canadian pneumococcal population over the course of this project, as was evident by the identification of numerous capsular switch variants. Capsule switching led to vaccine escape and increased diversity through acquisition of resistance determinants/MDR phenotypes not normally associated with certain serotypes. WGS was highly discriminatory and provided a wealth of information not normally accessible using traditional sub-typing methods. This tool will become increasingly important for elucidating genetic differences within the diverse pneumococcal population in Canada.en_US
dc.description.noteMay 2018en_US
dc.identifier.citationGolden AR, Adam HJ, Gilmour MW, Baxter MR, Martin I, Nichol KA, Demczuk WHB, Hoban DJ, Zhanel GG. Assessment of multidrug resistance, clonality and virulence in non-PCV-13 Streptococcus pneumoniae serotypes in Canada, 2011-13. J Antimicrob Chemother. 2015; 70(7): 1960-4.en_US
dc.identifier.citationGolden AR, Adam HJ, Zhanel GG, Canadian Antimicrobial Resistance Alliance. Invasive Streptococcus pneumoniae in Canada, 2011-14: Characterization of New Candidate 15-Valent Pneumococcal Conjugate Vaccine Serotypes 22F and 33F. Vaccine. 2016; 34(23): 2527-30.en_US
dc.identifier.urihttp://hdl.handle.net/1993/32885
dc.language.isoengen_US
dc.publisherOxford Academicen_US
dc.publisherElsevieren_US
dc.rightsopen accessen_US
dc.subjectInvasive Streptococcus pneumoniaeen_US
dc.subjectAntimicrobial Resistanceen_US
dc.subjectWhole genome sequencingen_US
dc.subjectCanadaen_US
dc.titleMolecular characterization of twelve predominant Streptococcus pneumoniae serotypes causing invasive infections in Canada from 2011 to 2015en_US
dc.typedoctoral thesisen_US
local.subject.manitobayesen_US
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