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Title: Quantification of the population structure of the pathogenic Bartonella species
Author: Chaloner, Gemma Louise
ISNI:       0000 0004 2736 7531
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2011
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Bartonella henselae is one of the most common zoonotic agents acquired from companion animals (cats) in industrialised countries. Nonetheless, given the high prevalence of infections in cats, the number of human infections reported is relatively low. One explanation for this discrepancy is that B. henselae strains vary in their zoonotic potential. To test the validity of this explanation, the population structure of B. henselae in the United Kingdom was quantified by applying multi- locus sequence typing (MLST) to a collection of isolates obtained by structured survey of cats living in the UK. The position of human-associated strains within this structure was then determined using MLST data obtained from infected human clinical material. A total of 13 MLST sequence types (STs) were identified among 98 feline isolates, with most (74%) belonging to ST4, ST6 and ST7. However, of the 23 human-associated strains characterized, most (85%) belonged to three genotypes, ST2, ST5 and ST8, which were rare amongst feline isolates. Differences in host association of ST2, ST5 and ST8 (human-associated) and ST 6 (feline) were statistically significant (P<0.05). Thus my data indicated that a few, uncommon STs were responsible for the majority of (symptomatic) human infections. Why certain STs are more frequently associated with zoonosis is uncertain; clearly, the ability to infect humans holds no selective advantage for B. henselae as humans are accidental hosts. Thus, this ability must be an unfortunate side effect of some other adaptation to part of the complex life cycle of B. henselae that involves chronic intra-erythrocytic parasitism in feline (reservoir) hosts, between which infection is transmitted by cat fleas. In an attempt to identify the stage of this life cycle in which zoonosis-associated strains consistently behaved in a manner different to other strains, I tested the performance of representative isolates of zoonosis-associated, and other STs in a series of assays previously developed as in vitro models for the various life cycle stages. Although differences were found in the growth kinetics and persistence of different isolates, variation in phenotype did not correlate with ST. I then exploited comparative genomics as an alternative approach to identifying differences between zoonosis-associated and other STs. This approach also allowed sensitive exploration of genomic variation within the species. SOLiD sequencing technology was used to generate sequence data for 16 B. henselae strains, which were compared by mapping to the previously-determined genome sequence of the type strain, Houston-I. I catalogued the modest variation in gene content within and between STs and identified 9013 genic SNPs within the dataset. Analysis of these SNPs allowed (i) the inference of a robust phylogeny that generally concurred with that of MLST data, (ii) the exploration of ongoing functional gene loss within the species, and (iii) the mapping of hotspots of selective pressure within the genomes. Further findings of this thesis include the molecular detection of Bartonella quintana in 12 endocarditis patients from the UK. Six ofthese patients were recent immigrants into the UK suggesting B. quintana is an important cause of endocarditis in UK immigrants. The use of MLST to determine the population structure of Bartonella species was extended to Bartonella bacilliformis, the aetiological agent of human bartonellosis, a disease of public health importance in Peru. A novel MLST scheme delineated 44 isolates into eight STs, some of which correlated with geographical provenance. Phylogenetic analysis revealed one ST, ST8, exhibited an evolutionary divergence from the other seven STs that was akin to that observed between other Bartonella species, suggesting ST8 strains are a novel Bartonella genospecies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available