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Hemophilus influenzae (Hi) has been an important strain in clinical examination, but it is not clear about its subtype, non-typable Hi, in causing invasive diseases after years of application of vaccines against typable Hi. Thus, the study is to determine the major infected bacterium causing invasive diseases and investigate the genotype relationship between antibiotic resistance and active IgA1 protease. Practical approaches of the study include clone each microorganism from infected blood, pus, sputum, bronchial washing and thorax samples of patients with invasive diseases. Each of the organisms was assayed for IgA1 protease activity, the type of the enzyme and antibiotic resistance. Forty-five patients aged 1 to over 71 with invasive diseases of diagnosed pneumonia, sinusitis, bacteremia, bronchitis, chronic obstructive of pulmonary diseases (COPD), conjunctivitis or otitis media, were analyzed, and all the 45 Hi isolates contain iga gene but only 80% contain active IgA1 protease. Mutations to silence iga gene are common in Hi isolates. The dominant population of infected bacterium is Hi, 84% of which are non-typable (NTHi). About 76% of NTHi and 85% of typable Hi (THi) contained active IgA1 protease. PFGE analysis showed that none of the 45 Hi isolates had identical genome. Phenotypes of active IgA1 protease and antibiotic resistance of the 45 Hi isolates showed no close relations each other. This study clearly demonstrated that NTHi has become a dominant strain in causing invasive diseases. Antibiotic resistance and active IgA1 protease are two essential but independent phenotypes for NTHi to infect and colonize. Antibiotic resistance of NTHi is dependent on the presence of beta-lactamase.

A general approach to the asymmetric syntheses of HETEs in both enantiomeric forms was developed. The syntheses of 8(S)-, 9(S)-, 11(S)- and 12(S)-HETE methyl esters, starting from D-arabinose, were accomplished. / A practical approach to the solution synthesis of fragments from Haemophilus influenzae type b capsular polymer was established, which opens a route to the development of a new vaccine against meningitis. The major aspects of this approach, stereocontrolled glycosidation, selective protection and deprotection, and efficient phosphorylation were detailed. The normal solution syntheses of the mono-, di- and tetrasaccharides were accomplished. / A new class of spacer for the linkage of the oligosaccharide with a protein was introduced. The spacer and the spacer-linked tetrasaccharide were prepared.

"March 2004" / Includes bibliographical references (leaves 213-272) / xxiii, 272 leaves ; ill. (some col.), plates ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Paediatrics, 2004