Why Do Some Human Associated Escherichia Coli Strains Lack Antibiotic Resistance?
E. coli ST lineages 131, 73 and 95 of phylogroup B2 are globally pathogenic, and are proportionally distributed in most hospital and community acquired human extra-intestinal diseases and in the gut. However, several pieces of evidence have shown that ST131 is highly multi-drug resistance while STs 73 and 95 are largely susceptible to antibiotics. Limited information exists to explain this. To investigate this, differences in the genomic diversity of plasmids in the lineages were characterised...[Show more]
|dc.description.abstract||E. coli ST lineages 131, 73 and 95 of phylogroup B2 are globally pathogenic, and are proportionally distributed in most hospital and community acquired human extra-intestinal diseases and in the gut. However, several pieces of evidence have shown that ST131 is highly multi-drug resistance while STs 73 and 95 are largely susceptible to antibiotics. Limited information exists to explain this. To investigate this, differences in the genomic diversity of plasmids in the lineages were characterised using bioinformatics tools. Plasmid-host dynamics were investigated by examining rate of plasmid transfers using plasmid transfer experiments. To assess the impacts of the plasmids on transfer rates, genome wide association studies were carried out, and to determine how well the plasmids are maintained within the host, stability experiments were done. Finally, fitness costs of the plasmid's carriage within the host over time using competition experiments and the evolutionary history existing among the two common F-plasmid sequence types were examined and compared using genome alignments techniques and phylogenetic analysis. ST73 lineage was observed to carry more of mobilizable plasmids compared to the other lineages. IncFII and IncFIB plasmids were common in the E. coli strains analysed. The presence of different classes of antimicrobial resistance genes and frequent occurrence of fluoroquinolone resistance determinant were observed in ST131. Most ST131 plasmids are associated with O25H4:fimH30, and the latter are adapted to multiple resistance genes and integrons, mostly detected in F-plasmid sequence type F29:A-:B10. ST95 and ST73 lineages also share this F-plasmid sequence type but most strains are associated with F51:A-:B10, which is also dominated by integrons, but fewer multiple antimicrobial genes. These lineages also encode many plasmid encoded virulence genes and bacteriocins. No diversity was observed in the rate of plasmid transfers among the ST lineages, however there were some variations between the F-plasmid sequence types and rates of plasmid transfer. This association was based on the presence of some variable genes: traC, traF, traH, traR found in the two plasmid types. The presence of the multiple tra genes positively enhanced the rates of plasmid transfer. Besides, the conjugal transfer, F-plasmid sequence type effects were also observed in plasmid stability frequencies and host fitness in all strains. Gene content of the two common F-plasmid sequence types revealed that the plasmids harboured about 74% of genes involved in IncF plasmid conjugative transfer. Other genes detected in these sequence types were mostly involved in plasmid stabilization, partition and regulation, regulators of plasmid encoded virulence genes, programmed cell death and operon control. The current study suggests that the success of plasmid-bacterium associations in ST73 and ST95 that made them globally pathogenic, even though antibiotic susceptible can be attributed majorly on the genetic content of the plasmids they encode, especially the F-plasmid sequence types, F51:A-:B10 and F29:A-:B10. These F-plasmid sequence types encode advantageous genes, are highly pathogenic, stable and exert minimal effects on the bacterial host that harbour them. This study has therefore demonstrated that plasmids associated with specific F-plasmid sequence type displayed genotypic characteristics indicative of adaptation, pathogenesis, and persistence in ExPEC diseases. The distinct functions of the tra genes encoded by these plasmids in conjugal transfer is pivotal in the adaptation, evolution, and survival of E. coli lineages and finally, the effects of F-plasmid sequence type on plasmid stability and host fitness play important roles on the ability of the plasmids to associate with new bacterial hosts and consequently on the evolution of plasmid-mediated antibiotic resistance.|
|dc.title||Why Do Some Human Associated Escherichia Coli Strains Lack Antibiotic Resistance?|
|Collections||Open Access Theses|
|Thesis- Veronica Alozie-chidi 14062022.pdf||Thesis Material||2.78 MB||Adobe PDF|
Items in Open Research are protected by copyright, with all rights reserved, unless otherwise indicated.