The mechanism of reduced human serum survival of Escherichia coli K1 RS218 by the eco60-63 operon

  • 廖 怡君

Student thesis: Master's Thesis

Abstract

Escherichia coli (E coli) K1 is one of the most common pathogens causing neonatal meningitis Since induction of bacteremia is a key step for the development of E coli meningitis characterizing the roles of the bacterial virulence factors when the pathogen is in the bloodstream would facilitate our understanding of the pathogenesis of this disease and contribute to the development of strategies against this disease The eco60-63 operon encoded by pRS218 a virulence plasmid of the E coli K1 strain RS218 known to be involved in the pathogenesis of E coli meningitis This operon has been shown to play an important role in the early stage of urinary tract infection (UTI) caused by E coli However our previous study showed that the expression of eco60-63 decreased the ability of RS218 to survive in the bloodstream and serum Thus in the present study I further investigated why the pathogenic E coli strain expressing this operon (eco60-63+ RS218) reduced resistance to serum killing than the strain without this operon (eco60-63- RS218) In normal human serum (NHS) eco60-63+ RS218 exhibited higher levels of C3b and membrane attack complex (MAC) deposition on the surface than eco60-63- RS218 suggesting that eco60-63+ RS218 encounters a higher level of complement-mediated attack in NHS than eco60-63- RS218 Blocking the activation of the classical or alternative complement pathways in NHS significantly decreased the difference of these two strains’ serum survival Also eco60-63+ RS218 exhibited higher levels of C1q IgG and properdin deposition in NHS than eco60-63- RS218 These findings suggested that eco60-63+ RS218 triggers stronger activation of the antibody-dependent classical and alternative complement pathways than eco60-63- RS218 Moreover expressing the eco60-63 operon may decrease RS218’s K1 capsule expression and increase this bacterium’s sensitivity to attack of membrane attack complex (MAC) The phenotypes induced by this operon may also contribute to the decreased serum survival caused by eco60-63 expression In addition expressing the eco60 gene alone decreased RS218’s serum survival ability while the expression of the other individual genes in the operon did not decrease the bacterium’s serum survival This suggested that eco60 plays a role in the differential serum killing of eco60-63+ RS218 and eco60-63- RS218 Although the eco60-63 operon hindered NMEC RS218 to survive in the serum RS218’s virulence plasmid still retains the operon A further study is required to determine whether the eco60-63 operon contributes to other pathogenesis steps of E coli meningitis The knowledge obtained from this study facilitates our understanding of E coli pathogenesis which may contribute to the development of novel strategies against E coli-caused infections in the future
Date of Award2015 Apr 9
Original languageEnglish
SupervisorChing-Hao Teng (Supervisor)

Cite this

The mechanism of reduced human serum survival of Escherichia coli K1 RS218 by the eco60-63 operon
怡君, 廖. (Author). 2015 Apr 9

Student thesis: Master's Thesis