title: Growth retardation, reduced invasiveness, and impaired colistin-mediated cell death associated with colistin resistance development in Acinetobacter baumannii.
abstract: Two colistin-susceptible/colistin-resistant (Col(s)/Col(r)) 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 Col(s) isolates (Ab248 and Ab299, both having a colistin MIC of 0.5 μg/ml), both Col(r) isolates (Ab249 and Ab347, with colistin MICs of 128 and 32 μg/ml, respectively) significantly overexpressed pmrCAB genes, had single-amino-acid shifts in the PmrB protein, and exhibited significantly slower growth. The Col(r) isolate Ab347, tested by proteomic analysis in comparison with its Col(s) 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. Col(s) 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 Col(r) isolates indistinguishable from Ab347 and Ab249 were mainly colonizers. In particular, a Col(s) isolate identical to Ab299 was still invading the bloodstream 90 days after the colonization of this patient by Col(r) isolates. These observations indicate considerably lower invasiveness of A. baumannii clinical isolates following the development of colistin resistance.
authors.affiliation: Department of Microbiology, Medical School, University of Athens, Athens, Greece.
authors.forename: Spyros
authors.initials: S
authors.lastname: Pournaras
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Poulou
authors.forename: Konstantina
authors.initials: K
authors.lastname: Dafopoulou
authors.forename: Yassine Nait
authors.initials: YN
authors.lastname: Chabane
authors.forename: Ioulia
authors.initials: I
authors.lastname: Kristo
authors.forename: Demosthenes
authors.initials: D
authors.lastname: Makris
authors.forename: Julie
authors.initials: J
authors.lastname: Hardouin
authors.forename: Pascal
authors.initials: P
authors.lastname: Cosette
authors.forename: Athanassios
authors.initials: A
authors.lastname: Tsakris
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Dé
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity; D000154:Aconitate Hydratase / Q000235:genetics / Q000378:metabolism; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002999:Clone Cells; D003091:Colistin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D008875:Middle Aged; D009876:Operon; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D054464:Peroxiredoxins; D002374:Catalase; D013482:Superoxide Dismutase; D000154:Aconitate Hydratase; D003091:Colistin