title: Impaired growth under iron-limiting conditions associated with the acquisition of colistin resistance in Acinetobacter baumannii.
abstract: Acquisition of colistin resistance in Acinetobacter baumannii has been associated with reduced bacterial fitness and virulence, although the mechanisms underlying this fitness loss have not been well characterised. In this study, the role played by environmental iron levels on the growth and survival of colistin-resistant strains of A. baumannii was assessed. Growth assays with the colistin-susceptible ATCC 19606 strain and its colistin-resistant derivative RC64 [colistin minimum inhibitory concentration (MIC) of 64 mg/L] demonstrated that the strains grew similarly in rich laboratory medium (Mueller-Hinton broth), whereas RC64 demonstrated impaired growth compared with ATCC 19606 in human serum (>100-fold at 24 h). Compared with RC64, ATCC 19606 grew in the presence of higher concentrations of the iron-specific chelator 2,2'-bipyridine and grew more readily under iron-limiting conditions in solid and liquid media. In addition, iron supplementation of human serum increased the growth of RC64 compared with unsupplemented human serum to a greater extent than ATCC 19606. The ability of 11 colistin-resistant clinical isolates with mutations in the pmrB gene to grow in iron-replete and iron-limiting conditions was assessed, demonstrating that eight of the strains showed reduced growth under iron limitation. Individual mutations in the pmrB gene did not directly correlate with a decreased capacity for growth under iron limitation, suggesting that mutations in pmrB may not directly produce this phenotype. Together these results indicate that acquisition of colistin resistance in A. baumannii can be associated with a decreased ability to grow in low-iron environments.
authors.affiliation: Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville 41013, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: López-Rojas
authors.affiliation: Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville 41013, Spain.
authors.forename: Meritxell
authors.initials: M
authors.lastname: García-Quintanilla
authors.affiliation: Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville 41013, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Labrador-Herrera
authors.affiliation: Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville 41013, Spain.
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Pachón
authors.affiliation: Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville 41013, Spain. Electronic address: mcconnell.mike75@gmail.com.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McConnell
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000254:growth & development*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D003091:Colistin / Q000494:pharmacology*; D003470:Culture Media / Q000737:chemistry; D024881:Drug Resistance, Bacterial; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D009154:Mutation; D044967:Serum / Q000737:chemistry; D014157:Transcription Factors / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003470:Culture Media; C409039:PmrB protein, bacteria; D014157:Transcription Factors; D007501:Iron; D003091:Colistin
keywords: Antibiotic resistance; Fitness; Iron; Virulence