Investigation of Gram-negative bacterial surface glycans: characterisation of Moraxella bovis lipooligosaccharide and progress towards developing a Nontypeable Haemophilus influenzae/Moraxella catarrhalis vaccine candidate

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Wilson, Jennifer

Grice, Irwin

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2019
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Abstract

Moraxella bovis, Moraxella catarrhalis and Nontypeable Haemophilus influenzae (NTHi) are Gram-negative, oxidase positive, pathogenic microorganisms. M. bovis causes Infectious Bovine Keratoconjunctivitis, known (IBK) as 'pink-eye' in cattle worldwide. The disease is of economic importance as it leads to substantial economic loss in the cattle and dairy industries. There are antibiotic treatments available to treat M. bovis associated infections, but they tend to be ineffective at controlling disease outbreaks. Importantly, the current series of antibiotics used to treat IBK have shown occurrence of resistance due to beta-lactamase enzyme produced by the bacteria. There does exist a pilin-based vaccine for IBK which has been approved for use in Australia, although it is problematic because it is not protective against all strains of M. bovis. M. catarrhalis and NTHi are human respiratory tract opportunistic pathogens responsible for otitis media in children and exacerbate chronic obstructive pulmonary disease in adults. Similar to M. bovis, both bacteria have been shown to produce [beta]-lactamase, which has led to the emergence of antibiotic resistance. There is no licenced vaccine for M. catarrhalis or NTHi infections. In the past two-decades studies on M. catarrhalis lipooligosaccharide (LOS) have suggested that this cell surface glycolipid could potentially be incorporated into vaccines. This is based on immunogenicity in a mouse model and role in adherence and invasion of host epithelia and serum resistance. It is also conserved among strains. M. bovis lipooligosaccharide (LOS) is not well studied. Structural analysis of wild-type M. bovis strain Epp63 oligosaccharide (OS from LOS) have identified the core OS as containing eleven sugar residues, including Kdo (the number of Kdo residues is still unknown) with a branched structure. Interestingly, this core OS has an unusual terminal open chain (1S)-GalaNAc residue and lacks heptose residues in its inner core. Recent studies have also elucidated the structure of the cell surface glycans in other strains (M. bovis Mb25 capsule and M. bovis Epp63 LOS), but whether the unusual structural features are present in other strains of M. bovis, was not known. This study elucidated the OS structure and identified the presence of capsular polysaccharide in M. bovis strains Mb25 and L183/2. [...]

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Thesis (PhD Doctorate)

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Doctor of Philosophy (PhD)

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School of Medical Science

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Subject

Pathogenic microorganisms

Moraxella bovis

Moraxella catarrhalis

Haemophilus influenzae

Vaccine

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