https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40844 Tue 19 Jul 2022 11:15:16 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43145 Tue 13 Sep 2022 15:21:31 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29749 Haemophilus influenzae is a host adapted human mucosal pathogen involved in a variety of acute and chronic respiratory tract infections, including chronic obstructive pulmonary disease and asthma, all of which rely on its ability to efficiently establish continuing interactions with the host. Here we report the characterization of a novel molybdenum enzyme, TorZ/MtsZ that supports interactions of H. influenzae with host cells during growth in oxygen-limited environments. Strains lacking TorZ/MtsZ showed a reduced ability to survive in contact with epithelial cells as shown by immunofluorescence microscopy and adherence/invasion assays. This included a reduction in the ability of the strain to invade human epithelial cells, a trait that could be linked to the persistence of H. influenzae. The observation that in a murine model of H. influenzae infection, strains lacking TorZ/MtsZ were almost undetectable after 72 h of infection, while ∼3.6 × 10³ CFU/mL of the wild type strain were measured under the same conditions is consistent with this view. To understand how TorZ/MtsZ mediates this effect we purified and characterized the enzyme, and were able to show that it is an S- and N-oxide reductase with a stereospecificity for S-sulfoxides. The enzyme converts two physiologically relevant sulfoxides, biotin sulfoxide and methionine sulfoxide (MetSO), with the kinetic parameters suggesting that MetSO is the natural substrate of this enzyme. TorZ/MtsZ was unable to repair sulfoxides in oxidized Calmodulin, suggesting that a role in cell metabolism/energy generation and not protein repair is the key function of this enzyme. Phylogenetic analyses showed that H. influenzae TorZ/MtsZ is only distantly related to the Escherichia coli TorZ TMAO reductase, but instead is a representative of a new, previously uncharacterized clade of molybdenum enzyme that is widely distributed within the Pasteurellaceae family of pathogenic bacteria. It is likely that MtsZ/TorZ has a similar role in supporting host/pathogen interactions in other members of the Pasteurellaceae, which includes both human and animal pathogens.]]> Thu 28 Oct 2021 12:36:21 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:3226 Sat 24 Mar 2018 07:22:15 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:3188 Sat 24 Mar 2018 07:21:57 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22284 Sat 24 Mar 2018 07:17:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39057 Fsp³ index natural-product analogues such as imino­sugars are of paramount importance in the investigation of their biological activities and reducing the use of protecting groups is an advantageous synthetic strategy. An iso­propyl­idene group was employed towards the synthesis of seven-membered ring imino­sugars and the title compound, C₉H₁₅N₃O₅, was crystallized as an inter­mediate, in which the THF ring is twisted and the dioxolane ring adopts an envelope conformation: the dihedral angle between the rings is 67.50 (13)°. In the crystal, the hydroxyl groups participate in O—H...(O,O) and O—H...N hydrogen-bonding inter­actions, which generate chains of mol­ecules propagating parallel to the a-axis direction. There is a notable non-classical C—H...O hydrogen bond, which cross-links the [100] chains into (001) sheets.]]> Mon 02 May 2022 15:27:38 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51500 Fri 08 Sep 2023 11:56:25 AEST ]]>