β-lactam resistance response triggered by inactivation of a nonessential penicillin-binding proteinβ-lactam电阻响应引发不必要的penicillin-binding蛋白质的失活.pdfVIP

b-Lactam Resistance Response Triggered by Inactivation of a Nonessential Penicillin-Binding Protein ´ 1 ¨ 2 1 ´ ´ 3 1 Bartolome Moya , Andreas Dotsch , Carlos Juan , Jesus Blazquez , Laura Zamorano , Susanne 2 1 Haussler , Antonio Oliver * ´ ´ ´ 1 Servicio de Microbiologıa and Unidad de Investigacion, Hospital Son Dureta, Instituto Universitario de Investigacion en Ciencias de la Salud (IUNICS) Palma de Mallorca, ´ ´ Spain, 2 Helmholtz Centre for Infection Research, Braunschweig, Germany, 3 Centro Nacional de Biotecnologıa, Consejo Superior de Investigaciones Cientıficas (CSIC), Campus UAM, Madrid, Spain Abstract It has long been recognized that the modification of penicillin-binding proteins (PBPs) to reduce their affinity for b-lactams is an important mechanism (target modification) by which Gram-positive cocci acquire antibiotic resistance. Among Gram- negative rods (GNR), however, this mechanism has been considered unusual, and restricted to clinically irrelevant laboratory mutants for most species. Using as a model Pseudomonas aeruginosa, high up on the list of pathogens causing life- threatening infections in hospitalized patients worldwide, we show that PBPs may also play a major role in b-lactam resistance in GNR, but through a totally distinct mechanism. Through a detailed genetic investigation, including whole- genome analysis approaches, we demonstrate that high-level (clinica