Crystal structure of MexZ, a key repressor responsible for antibiotic resistance in Pseudomonas aeruginosa.
Pseudomonas aeruginosa is responsible for around 10% of all hospital-acquired infections and the single most important pathogen of cystic fibrosis lungs. P. aeruginosa has high intrinsic and acquired antibiotic resistance, due to the extrusion of antibiotics by multidrug efflux pumps. The gene regulator MexZ controls the expression of mexXY, the efflux pump responsible for resistance to many drugs that are used for treating CF patients. MexZ is shown to be the most frequently mutated gene in P. aeruginosa isolated from CF patient lungs, confirming its importance in multidrug resistance. Here we present the crystal structure of MexZ at 2.9Å. Combining the structural information with biochemical data on key mutants identified, we provide an explanation for the structural and functional consequences of these mutants. This work provides a framework for further characterisation of MexZ in order to fully understand its regulation and induction.
Alguel
Yilmaz
Y
Division of Molecular Biosciences and Centre for Structural Biology, Imperial College London, London SW7 2AZ, United Kingdom.
Lu
Duo
D
Quade
Nick
N
Sauter
Sebastian
S
Zhang
Xiaodong
X
D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D003550:Cystic Fibrosis / Q000382:microbiology; D004247:DNA / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D006801:Humans; D008168:Lung / Q000382:microbiology; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; C402791:MexXY protein, Pseudomonas aeruginosa; C402792:MexZ protein, Pseudomonas aeruginosa; D004247:DNA