title: Pseudomonas aeruginosa AmpR: an acute-chronic switch regulator.
abstract: Pseudomonas aeruginosa is one of the most intractable human pathogens that pose serious clinical challenge due to extensive prevalence of multidrug-resistant clinical isolates. Armed with abundant virulence and antibiotic resistance mechanisms, it is a major etiologic agent in a number of acute and chronic infections. A complex and intricate network of regulators dictates the expression of pathogenicity factors in P. aeruginosa. Some proteins within the network play key roles and control multiple pathways. This review discusses the role of one such protein, AmpR, which was initially recognized for its role in antibiotic resistance by regulating AmpC β-lactamase. Recent genomic, proteomic and phenotypic analyses demonstrate that AmpR regulates expression of hundreds of genes that are involved in diverse pathways such as β-lactam and non-β-lactam resistance, quorum sensing and associated virulence phenotypes, protein phosphorylation, and physiological processes. Finally, ampR mutations in clinical isolates are reviewed to shed light on important residues required for its function in antibiotic resistance. The prevalence and evolutionary implications of AmpR in pathogenic and nonpathogenic proteobacteria are also discussed. A comprehensive understanding of proteins at nodal positions in the P. aeruginosa regulatory network is crucial in understanding, and ultimately targeting, the pathogenic stratagems of this organism.
authors: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
authors: Deepak
authors: D
authors: Balasubramanian
authors: Department of Human & Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.
authors: Hansi
authors: H
authors: Kumari
authors: Department of Human & Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA Kalai.Mathee@fiu.edu.
authors: Kalai
authors: K
authors: Mathee
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000502:physiology*; D018085:Regulon
chemical_list: D001426:Bacterial Proteins; C071526:AmpR protein, Bacteria
keywords: Pseudomonas aeruginosa virulence; antibiotic resistance; c-di-GMP; global regulator; quorum sensing; ser/thr protein phosphorylation