2-Aminoimidazole Analogs Target PhoP Altering DNA Binding Activity and Affect Outer Membrane Stability in Gram-Negative Bacteria.

Autor: Zeczycki TN; Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina27834, United States., Milton ME; Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina27834, United States., Jung D; Agile Sciences Inc., 617 Hutton Street, Raleigh, North Carolina27606, United States., Thompson RJ; Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina27834, United States., Jaimes FE; Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina27834, United States., Hondros AD; Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina27834, United States., Palethorpe S; Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, North Carolina27834, United States., Melander C; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana46556, United States., Cavanagh J; Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina27834, United States.
Jazyk: angličtina
Zdroj: Biochemistry [Biochemistry] 2022 Dec 20; Vol. 61 (24), pp. 2948-2960. Date of Electronic Publication: 2022 Dec 01.
DOI: 10.1021/acs.biochem.2c00560
Abstrakt: Multidrug-resistant bacteria cause immense public health concerns as once effective antibiotics no longer work against even common infections. Concomitantly, there has been a decline in the discovery of new antibiotics, and the current global clinical pipeline is woefully inadequate, especially against resistant Gram-negative bacteria. One major contribution to Gram-negative resistance is the presence of a protective outer membrane. Consequently, an appealing option for tackling resistance is to adversely affect that outer membrane. With that in mind, we define the response regulator PhoP as a target for new 2-aminoimidazole compounds and show that they affect the integrity of the outer membrane in resistant strains of Escherichia coli and Klebsiella pneumoniae . We also provide empirical evidence for the 2-aminoimidazole mechanism of action.
Databáze: MEDLINE
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