https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37942 Acinetobacter baumannii. Our analyses reveal that AA and DHA incorporate into the A. baumannii bacterial membrane and impact bacterial fitness and membrane integrity, with DHA having a more pronounced effect. Through transcriptional profiling and mutant analyses, we show that the A. baumannii β-oxidation pathway plays a protective role against AA and DHA, by limiting their incorporation into the phospholipids of the bacterial membrane. Furthermore, our study identified a second bacterial membrane protection system mediated by the AdeIJK efflux system, which modulates the lipid content of the membrane via direct efflux of lipids other than AA and DHA, thereby providing a novel function for this major efflux system in A. baumannii This is the first study to examine the antimicrobial effects of host fatty acids on A. baumannii and highlights the potential of AA and DHA to protect against A. baumannii infections.Importance: A shift in the Western diet since the industrial revolution has resulted in a dramatic increase in the consumption of omega-6 fatty acids, with a concurrent decrease in the consumption of omega-3 fatty acids. This decrease in omega-3 fatty acid consumption has been associated with significant disease burden, including increased susceptibility to infectious diseases. Here we provide evidence that DHA, an omega-3 fatty acid, has superior antimicrobial effects upon the highly drug-resistant pathogen Acinetobacter baumannii, thereby providing insights into one of the potential health benefits of omega-3 fatty acids. The identification and characterization of two novel bacterial membrane protective mechanisms against host fatty acids provide important insights into A. baumannii adaptation during disease. Furthermore, we describe a novel role for the major multidrug efflux system AdeIJK in A. baumannii membrane maintenance and lipid transport. This core function, beyond drug efflux, increases the appeal of AdeIJK as a therapeutic target.]]> Mon 05 Jul 2021 16:17:04 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40169 in vitro model of the pulmonary epithelial-endothelial barrier and novel murine models to investigate the role of glycemic variability in influenza severity. In vitro, a history of glycemic variability significantly increased influenza-driven cell death and destruction of the epithelial-endothelial barrier. In vivo, influenza virus-infected mice with a history of glycemic variability lost significantly more body weight than mice with constant blood glucose levels. This increased disease severity was associated with markers of oxidative stress and hyperinflammation both in vitr and in vivo. Together, these results provide the first indication that glycemic variability may help drive the increased risk of severe influenza in people with diabetes mellitus.]]> Fri 15 Jul 2022 10:39:14 AEST ]]>