title: [Antibiotic-dependent selection of the E. coli clones with increased chaperone activity for highly-efficient production of the full-length soluble New Delhi metallo-beta-lactamase].
abstract: The spread of the New Delhi metallo-beta-lactamase (NDM-1), a plasmid-borne enzyme conferring bacterial resistance to any known beta-lactam antibiotics, represents the global health threat. There is an urgent need to develop the efficient NDM-1 inhibitors of various mode of action thereby necessitating structural studies of the enzyme as well as analysis of the secretion pathway and localization of the protein. The recombinant full-length NDM-1 is produced in E. coli in the inactive form and is mostly accumulated in the inclusion bodies. The secreted recombinant NDM-1 forms are several N-terminally truncated species. The robust expression system capable of high-level production of the full-length NDM-1 and derivatives thereof is required to obtain NDM-1 in the quantities necessary for drug discovery, diagnostics, and research purposes. Therefore, we developed a new system that utilizes antibiotic pressure to select E. coli producing increased quantity of soluble NDM-1 and showed that an increase in the NDM-1 solubility occurs in the bacterial clones producing increased amounts in the chaperones.
authors.forename: A V
authors.initials: AV
authors.lastname: Kozyr'
authors.forename: N M
authors.initials: NM
authors.lastname: Luneva
authors.forename: A E
authors.initials: AE
authors.lastname: Khlyntseva
authors.forename: I G
authors.initials: IG
authors.lastname: Shemiakin
authors.forename: O N
authors.initials: ON
authors.lastname: Krasavtseva
authors.forename: A V
authors.initials: AV
authors.lastname: Kolesnikov
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D018832:Molecular Chaperones / Q000096:biosynthesis* / Q000235:genetics; D010957:Plasmids; D018440:beta-Lactam Resistance / Q000235:genetics*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics; D047090:beta-Lactams / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D018832:Molecular Chaperones; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D001618:beta-Lactamases; C552864:beta-lactamase NDM-1