Biochemistry Seminar (Please Note Zoom Only)
"PmrAB, the Two-component System of Acinetobacter Baumannii, Controls the Phosphoethanolamine Modification of Lipooligosaccharide in Response to Metal Ions"
Zoom Link:
https://notredame.zoom.us/j/94259169597?pwd=3qxqcOBl6NA4D9gaNARusotzaFDbI1.1
Meeting ID: 942 5916 9597
Passcode: 238876
Abstract: Antibiotic resistance is on the rise and deteriorating the efficacy of our treatment options for severe bacterial infections. Extremely drug-resistant (XDR) Acinetobacter baumannii is particularly concerning because it is resistant to polymyxins, the last resort drug for XDR Gram-negative infections, and has become more widespread. Polymyxin resistance in A. baumannii is mainly caused by mutations in pmrAB that increase activation. This leads to lipooligosaccharide modifications that contribute to polymyxin resistance. However, its function as a TCS has not been fully elucidated and neither has its regulatory genes and response factors. To identify the regulatory genes of PmrAB a transcriptome analysis was done using A. baumannii strains that carried clinical pmrAB mutations. b-galactosidase activity was also measured to identify the response factors that trigger pmrAB activation. They found 18 genes that are regulated by PmrAB and are associated with LOS modification and polysaccharide synthesis. PmrAB was also found to contain a novel ExxxE motif , in addition to the known ExxE motif, that is involved in the response to low pH and metal ions, such as Al3+, Fe2+, and Zn2+. These results demonstrate that PmrAB not only regulates genes that play a role in LOS modification but also responds to factors such as pH and metal ions, together this leads to increased polymyxin resistance. This study highlights the importance of understanding how PmrAB plays a role in environmental adaptation and how that is tied to the emergence of XDR A. baumannii.
Citation: Yamada N, et al. PmrAB, the two-component system of Acinetobacter baumannii, controls the phosphoethanolamine modification of lipooligosaccharide in response to metal ions. J Bacteriol 2024, 206, 5. https://doi.org/10.1128/jb.00435-23