TY - JOUR
TI - Growth retardation, reduced invasiveness, and impaired colistin-mediated cell death associated with colistin resistance development in Acinetobacter baumannii
AU - Pournaras, S.
AU - Poulou, A.
AU - Dafopoulou, K.
AU - Chabane, Y.N.
AU - Kristo, I.
AU - Makris, D.
AU - Hardouin, J.
AU - Cosette, P.
AU - Tsakris, A.
AU - Dé, E.
JO - Antimicrobial Agents and Chemotherapy
PY - 2014
VL - 58
TODO - 2
SP - 828-832
PB - 
SN - 0066-4804, 1098-6596
TODO - 10.1128/AAC.01439-13
TODO - carbapenem;  ciprofloxacin;  colistin;  genomic DNA;  gentamicin;  imipenem;  meropenem;  metronidazole;  rifampicin;  RNA;  RNA 16S;  sultamicillin;  teicoplanin;  tigecycline, Acinetobacter baumannii;  adult;  aged;  antibiotic resistance;  antibiotic therapy;  article;  bacterial cell;  bacterial gene;  bacterial virulence;  bacterium culture;  bloodstream infection;  case report;  cell death;  colony forming unit;  coronary artery bypass surgery;  critically ill patient;  gene expression;  hospital infection;  human;  intensive care unit;  mediastinitis;  middle aged;  minimum inhibitory concentration;  nonhuman;  polymerase chain reaction;  priority journal;  protein expression;  proteomics;  sternotomy, Acinetobacter baumannii;  Acinetobacter Infections;  Aconitate Hydratase;  Aged;  Anti-Bacterial Agents;  Bacterial Proteins;  Catalase;  Clone Cells;  Colistin;  Drug Resistance, Bacterial;  Gene Expression Regulation, Bacterial;  Humans;  Microbial Sensitivity Tests;  Microbial Viability;  Middle Aged;  Operon;  Peroxiredoxins;  Superoxide Dismutase
TODO - Two colistin-susceptible/colistin-resistant (Cols/Colr) pairs of Acinetobacter baumannii strains assigned to international clone 2, which is prevalent worldwide, were sequentially recovered from two patients after prolonged colistin administration. Compared with the respective Cols isolates (Ab248 and Ab299, both having a colistin MIC of 0.5 g/ml), both Colr isolates (Ab249 and Ab347, with colistin MICs of 128 and 32 g/ml, respectively) significantly overexpressed pmrCAB genes, had single-aminoacid shifts in the PmrB protein, and exhibited significantly slower growth. The Colr isolate Ab347, tested by proteomic analysis in comparison with its Cols counterpart Ab299, underexpressed the proteins CsuA/B and C from the csu operon (which is necessary for biofilm formation). This isolate also underexpressed aconitase B and different enzymes involved in the oxidative stress response (KatE catalase, superoxide dismutase, and alkyl hydroperoxide reductase), suggesting a reduced response to reactive oxygen species (ROS) and, consequently, impaired colistin-mediated cell death through hydroxyl radical production. Cols isolates that were indistinguishable by macrorestriction analysis from Ab299 caused six sequential bloodstream infections, and isolates indistinguishable from Ab248 caused severe soft tissue infection, while Colr isolates indistinguishable from Ab347 and Ab249 were mainly colonizers. In particular, a Cols isolate identical to Ab299 was still invading the bloodstream 90 days after the colonization of this patient by Colr isolates. These observations indicate considerably lower invasiveness of A. baumannii clinical isolates following the development of colistin resistance. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
ER -