https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45284 Wed 26 Oct 2022 17:20:38 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50035 Wed 24 Jan 2024 15:36:26 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35705 Acinetobacter baumannii causes severe, fulminant, community-acquired pneumonia (CAP) in tropical and subtropical regions. We compared the population structure, virulence and antimicrobial resistance determinants of northern Australian community-onset A. baumannii strains with local and global strains. We performed whole-genome sequencing on 55 clinical and five throat colonization A. baumannii isolates collected in northern Australia between 1994 and 2016. Clinical isolates included CAP (n=41), healthcare-associated pneumonia (n=7) and nosocomial bloodstream (n=7) isolates. We also included 93 publicly available international A. baumannii genome sequences in the analyses. Patients with A. baumannii CAP were almost all critically unwell; 82 % required intensive care unit admission and 18 % died during their inpatient stay. Whole-genome phylogenetic analysis demonstrated that community-onset strains were not phylogenetically distinct from nosocomial strains. Some non-multidrug-resistant local strains were closely related to multidrug-resistant strains from geographically distant locations. Pasteur sequence type (ST)10 was the dominant ST and accounted for 31/60 (52 %) northern Australian strains; the remainder belonged to a diverse range of STs. The most recent common ancestor for ST10 was estimated to have occurred in 1738 (95 % highest posterior density, 1626–1826), with evidence of multiple introduction events between Australia and Southeast Asia between then and the present day. Virulence genes associated with biofilm formation and the type 6 secretion system (T6SS) were absent in many strains, and were not associated with in-hospital mortality. All strains were susceptible to gentamicin and meropenem; none carried an AbaR resistance island. Our results suggest that international dissemination of A. baumannii is occurring in the community on a contemporary timescale. Genes associated with biofilm formation and the T6SS may not be required for survival in community niches. The relative contributions of host and bacterial factors to the clinical severity of community-onset A. baumannii infection require further investigation.]]> Wed 15 Dec 2021 16:09:07 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:55368 Tue 21 May 2024 09:42:55 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:55147 256 mg/L) revealed modified expression of several genes related to membrane transport (porin ompK36 and efflux pump regulator oqxR) and nitroreductase activity (ribC and nfsB, involved in nitrofurantoin reduction). Untargeted metabolomics analysis of total metabolites extracted at 1 and 4 h post-nitrofurantoin treatment revealed that exposure to the drug caused a delayed effect on the metabolome which was most pronounced after 4 h. Pathway enrichment analysis illustrated that several complex interrelated metabolic pathways related to nitrofurantoin bacterial killing (aminoacyl-tRNA biosynthesis, purine metabolism, central carbohydrate metabolism, and pantothenate and CoA biosynthesis) and the development of nitrofurantoin resistance (riboflavin metabolism) were significantly perturbed. This study highlights for the first time the key role of efflux pump regulator oqxR in nitrofurantoin resistance and reveals global metabolome perturbations in response to nitrofurantoin, in K. pneumoniae.]]> Tue 16 Apr 2024 15:16:15 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50476 Tue 14 Nov 2023 15:04:31 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35003 Tue 03 Sep 2019 17:52:20 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40048 Thu 21 Jul 2022 10:30:22 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45522 Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The combination of polymyxin B and sertraline showed synergistic antibacterial activity in checkerboard and static time-kill assays at clinically relevant concentrations against both polymyxin-susceptible and polymyxin-resistant isolates. The potential antimicrobial mode of action of the combination was investigated against P.aeruginosa FADDI-PA024 using untargeted metabolomics alongside scanning and transmission electron microscopy (EM). Scanning and transmission EM revealed that the polymyxin B and sertraline combination resulted in greater damage to the bacterial cell compared to each drug alone. Metabolomics results showed that the combination significantly affected the bacterial ability to remodel its outer membrane. This was reflected by the major perturbation of glycerophospholipids and fatty acids and the pantothenate and coenzyme A (CoA) pathways, which feed fatty acid elongation (e.g., trans-hexadec-2-enoyl-CoA) as well as inhibit the biosynthesis of lipopolysaccharide and peptidoglycan. The combination also inhibited the polymyxin resistance phosphoethanolamine (pEtN) lipid A modification pathway, indicated by the declined levels of phosphoethanolamine. In summary, the present study highlights the potential possibilities of a polymyxin-sertraline combination for the treatment of infections caused by multidrug resistant Gram-negative bacteria such as central nervous system (CNS) infections via direct intraventricular/intrathecal delivery.]]> Mon 31 Oct 2022 14:09:59 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54174 Mon 12 Feb 2024 09:35:16 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39571 Mon 08 Aug 2022 11:34:21 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42580 Fri 26 Aug 2022 08:13:57 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51333 Fri 01 Sep 2023 10:11:17 AEST ]]>