title: In Vivo Selection of Pan-Drug Resistant Acinetobacter baumannii during Antibiotic Treatment.
abstract: OBJECTIVE
  Colistin resistance in Acinetobacter baumannii (A. baumannii) is mediated by a complete loss of lipopolysaccharide production via mutations in lpxA, lpxC, and lpxD gene or lipid A modifications via mutations in the pmrA and pmrB genes. However, the exact mechanism of therapy-induced colistin resistance in A. baumannii is not well understood.
  
  
  METHODS
  We investigated the genotypic and phenotypic changes that underlie pan-drug resistance mechanisms by determining differences between the alterations in extensively drug-resistant (XDR) A. baumannii (AB001 and AB002) isolates and a pan-drug resistant (PDR) counterpart (AB003) recovered from one patient before and after antibiotic treatment, respectively.
  
  
  RESULTS
  All three clinical isolates shared an identical sequence type (ST138), belonging to the global epidemic clone, clonal complex 92, and all produced OXA-23 carbapenemase. The PDR AB003 showed two genetic differences, acquisition of armA gene and an amino acid substitution (Glu229Asp) in pmrB gene, relative to XDR isolates. No mutations were detected in the pmrA, pmrC, lpxA, lpxC, or lpxD genes in all three isolates. In matrix-assisted laser desorption ionization-time of flight analysis, the three isolates commonly showed two major peaks at 1728 m/z and 1912 m/z, but peaks at 2034 m/z, 2157 m/z, 2261 m/z, and 2384 m/z were detected only in the PDR A. baumannii AB003 isolate.
  
  
  CONCLUSIONS
  Our results show that changes in lipid A structure via a mutation in the pmrB gene and acquisition of armA gene might confer resistance to colistin and aminoglycosides to XDR A. baumannii strains, resulting in appearance of a PDR A. baumannii strain of ST138.
authors.affiliation: Department of Laboratory Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Yoonjung
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Dental Hygiene, Silla University, Busan, Korea.
authors.forename: Il Kwon
authors.initials: IK
authors.lastname: Bae
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Korea. kscpjsh@yuhs.ac.
authors.forename: Seok Hoon
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Dongeun
authors.initials: D
authors.lastname: Yong
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kyungwon
authors.initials: K
authors.lastname: Lee
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics*; D003091:Colistin / Q000494:pharmacology* / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial; D016521:Electrophoresis, Gel, Pulsed-Field; D005838:Genotype; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D058889:Molecular Typing; D009154:Mutation; D016133:Polymerase Chain Reaction; D014157:Transcription Factors; D001618:beta-Lactamases
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C409039:PmrB protein, bacteria; D014157:Transcription Factors; C081902:pmrA protein, Bacteria; D001618:beta-Lactamases; C063912:carbapenemase; D003091:Colistin
keywords: Acinetobacter baumannii; armA gene; colistin; lipid A; pmrB gene