?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.title=Morphologic+and+genomic+characterisation+of+the+koala+Chlamydia+pneumoniae+strain&rft.creator=Mitchell%2C+Candice+Melissa&rft.subject=Chlamydia+pneumoniae%2C+Chlamydia%2C+pathogen%2C+respiratory%2C+characterisation%2C+developmental+cycle%2C+elementary+body%2C+reticulate+body%2C+inclusion+morphology%2C+genome%2C+genomic+comparison%2C+bioinformatics%2C+single+nucleotide+polymorphism%2C+SNP%2C+PCR%2C+gene+sequencing&rft.description=Chlamydia+pneumoniae+is+a+common+human+and+animal+pathogen+associated+with+a+wide+range+of+upper+and+lower+respiratory+tract+infections.+In+more+recent+years+there+has+been+increasing+evidence+to+suggest+a+link+between+C.+pneumoniae+and+chronic+diseases+in+humans%2C+including+atherosclerosis%2C+stroke+and+Alzheimer%E2%80%99s+disease.+C.+pneumoniae+human+strains+show+little+genetic+variation%2C+indicating+that+the+human-derived+strain+originated+from+a+common+ancestor+in+the+recent+past.+Despite+extensive+information+on+the+genetics+and+morphology+processes+of+the+human+strain%2C+knowledge+concerning+many+other+hosts+(including+marsupials%2C+amphibians%2C+reptiles+and+equines)+remains+virtually+unexplored.+The+koala+(Phascolarctos+cinereus)+is+a+native+Australian+marsupial+under+threat+due+to+habitat+loss%2C+predation+and+disease.+Koalas+are+very+susceptible+to+chlamydial+infections%2C+most+commonly+affecting+the+conjunctiva%2C+urogenital+tract+and%2For+respiratory+tract.+To+address+this+gap+in+the+literature%2C+the+present+study+(i)+provides+a+detailed+description+of+the+morphologic+and+genomic+architecture+of+the+C.+pneumoniae+koala+(and+human)+strain%2C+and+shows+that+the+koala+strain+is+microscopically%2C+developmentally+and+genetically+distinct+from+the+C.+pneumoniae+human+strain%2C+and+(ii)+examines+the+genetic+relationship+of+geographically+diverse+C.+pneumoniae+isolates+from+human%2C+marsupial%2C+amphibian%2C+reptilian+and+equine+hosts%2C+and+identifies+two+distinct+lineages+that+have+arisen+from+animal-to-human+cross+species+transmissions.+Chapter+One+of+this+thesis+explores+the+scientific+problem+and+aims+of+this+study%2C+while+Chapter+Two+provides+a+detailed+literature+review+of+the+background+in+this+field+of+work.+Chapter+Three%2C+the+first+results+chapter%2C+describes+the+morphology+and+developmental+stages+of+C.+pneumoniae+koala+isolate+LPCoLN%2C+as+revealed+by+fluorescence+and+transmission+electron+microscopy.+The+profile+of+this+isolate%2C+when+cultured+in+HEp-2+human+epithelial+cells%2C+was+quite+different+to+the+human+AR39+isolate.+Koala+LPCoLN+inclusions+were+larger%3B+the+elementary+bodies+did+not+have+the+characteristic+pear-shaped+appearance%2C+and+the+developmental+cycle+was+completed+within+a+shorter+period+of+time+(as+confirmed+by+quantitative+real-time+PCR).+These+in+vitro+findings+might+reflect+biological+differences+between+koala+LPCoLN+and+human+AR39+in+vivo.+Chapter+Four+describes+the+complete+genome+sequence+of+the+koala+respiratory+pathogen%2C+C.+pneumoniae+LPCoLN.+This+is+the+first+animal+isolate+of+C.+pneumoniae+to+be+fully-sequenced.+The+genome+sequence+provides+new+insights+into+genomic+%E2%80%98plasticity%E2%80%99+(organisation)%2C+evolution+and+biology+of+koala+LPCoLN%2C+relative+to+four+complete+C.+pneumoniae+human+genomes+(AR39%2C+CWL029%2C+J138+and+TW183).+Koala+LPCoLN+contains+a+plasmid+that+is+not+shared+with+any+of+the+human+isolates%2C+there+is+evidence+of+gene+loss+in+nucleotide+salvage+pathways%2C+and+there+are+10+hot+spot+genomic+regions+of+variation+that+were+previously+not+identified+in+the+C.+pneumoniae+human+genomes.+Sequence+(partial-length)+from+a+second%2C+independent%2C+wild+koala+isolate+(EBB)+at+several+gene+loci+confirmed+that+the+koala+LPCoLN+isolate+was+representative+of+a+koala+C.+pneumoniae+strain.+The+combined+sequence+data+provides+evidence+that+the+C.+pneumoniae+animal+(koala+LPCoLN)+genome+is+ancestral+to+the+C.+pneumoniae+human+genomes+and+that+human+infections+may+have+originated+from+zoonotic+infections.+Chapter+Five+examines+key+genome+components+of+the+five+C.+pneumoniae+genomes+in+more+detail.+This+analysis+reveals+genomic+features+that+are+shared+by+and%2For+contribute+to+the+broad+ecological+adaptability+and+evolution+of+C.+pneumoniae.+This+analysis+resulted+in+the+identification+of+65+gene+sequences+for+further+analysis+of+intraspecific+variation%2C+and+revealed+some+interesting+differences%2C+including+fragmentation%2C+truncation+and+gene+decay+(loss+of+redundant+ancestral+traits).+This+study+provides+valuable+insights+into+metabolic+diversity%2C+adaptation+and+evolution+of+C.+pneumoniae.+Chapter+Six+utilises+a+subset+of+23+target+genes+identified+from+the+previous+genomic+comparisons+and+makes+a+significant+contribution+to+our+understanding+of+genetic+variability+among+C.+pneumoniae+human+(11)+and+animal+(6+amphibian%2C+5+reptilian%2C+1+equine+and+7+marsupial+hosts)+isolates.+It+has+been+shown+that+the+animal+isolates+are+genetically+diverse%2C+unlike+the+human+isolates+that+are+virtually+clonal.+More+convincing+evidence+that+C.+pneumoniae+originated+in+animals+and+recently+(in+the+last+few+hundred+thousand+years)+crossed+host+species+to+infect+humans+is+provided+in+this+study.+It+is+proposed+that+two+animal-to-human+cross+species+events+have+occurred+in+the+context+of+the+results%2C+one+evident+by+the+nearly+clonal+human+genotype+circulating+in+the+world+today%2C+and+the+other+by+a+more+animal-like+genotype+apparent+in+Indigenous+Australians.+Taken+together%2C+these+data+indicate+that+the+C.+pneumoniae+koala+LPCoLN+isolate+has+morphologic+and+genomic+characteristics+that+are+distinct+from+the+human+isolates.+These+differences+may+affect+the+survival+and+activity+of+the+C.+pneumoniae+koala+pathogen+in+its+natural+host%2C+in+vivo.+This+study%2C+by+utilising+the+genetic+diversity+of+C.+pneumoniae%2C+identified+new+genetic+markers+for+distinguishing+human+and+animal+isolates.+However%2C+not+all+C.+pneumoniae+isolates+were+genetically+diverse%3B+in+fact%2C+several+isolates+were+highly+conserved%2C+if+not+identical+in+sequence+(i.e.+Australian+marsupials)+emphasising+that+at+some+stage+in+the+evolution+of+this+pathogen%2C+there+has+been+an+adaptation%2Fs+to+a+particular+host%2C+providing+some+stability+in+the+genome.+The+outcomes+of+this+study+by+experimental+and+bioinformatic+approaches+have+significantly+enhanced+our+knowledge+of+the+biology+of+this+pathogen+and+will+advance+opportunities+for+the+investigation+of+novel+vaccine+targets%2C+antimicrobial+therapy%2C+or+blocking+of+pathogenic+pathways.&rft.publisher=Queensland+University+of+Technology&rft.date=2010&rft.type=Thesis&rft.format=application%2Fpdf&rft.relation=https%3A%2F%2Feprints.qut.edu.au%2F33259%2F1%2FCandice_Mitchell_Thesis.pdf&rft.rights=free_to_read&rft.format=application%2Fpdf&rft.relation=https%3A%2F%2Feprints.qut.edu.au%2F33259%2F3%2FSupplementary_Material_Chapter_Five.pdf&rft.format=application%2Fpdf&rft.relation=https%3A%2F%2Feprints.qut.edu.au%2F33259%2F4%2FSupplementary_Material_Chapter_Six.pdf&rft.format=application%2Fpdf&rft.relation=https%3A%2F%2Feprints.qut.edu.au%2F33259%2F2%2FCandice_Mitchell_Citation.pdf&rft.relation=Mitchell%2C+Candice+Melissa+(2010)+Morphologic+and+genomic+characterisation+of+the+koala+Chlamydia+pneumoniae+strain.+PhD+by+Publication%2C+Queensland+University+of+Technology.&rft.id_number=https%3A%2F%2Feprints.qut.edu.au%2F33259%2F&rft.identifier=Faculty+of+Science+and+Technology%3B+Institute+of+Health+and+Biomedical+Innovation