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In Vivo Selection of Pan-Drug Resistant Acinetobacter baumannii during Antibiotic Treatment

 Yoonjung Kim  ;  Il Kwon Bae  ;  Seok Hoon Jeong  ;  Dongeun Yong  ;  Kyungwon Lee 
 YONSEI MEDICAL JOURNAL, Vol.56(4) : 928-934, 2015 
Journal Title
Issue Date
Acinetobacter Infections/drug therapy* ; Acinetobacter Infections/microbiology ; Acinetobacter baumannii/drug effects* ; Acinetobacter baumannii/genetics* ; Acinetobacter baumannii/isolation & purification ; Aged ; Anti-Bacterial Agents/pharmacology* ; Anti-Bacterial Agents/therapeutic use ; Bacterial Proteins/genetics* ; Colistin/pharmacology* ; Colistin/therapeutic use ; Drug Resistance, Bacterial* ; Electrophoresis, Gel, Pulsed-Field ; Genotype ; Humans ; Male ; Microbial Sensitivity Tests ; Molecular Typing ; Mutation ; Polymerase Chain Reaction ; Transcription Factors ; beta-Lactamases
Acinetobacter baumannii ; armA gene ; colistin ; lipid A ; pmrB gene
PURPOSE: 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. MATERIALS AND 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. CONCLUSION: 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.
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1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Yoon Jung(김윤정) ORCID logo https://orcid.org/0000-0002-4370-4265
Yong, Dong Eun(용동은) ORCID logo https://orcid.org/0000-0002-1225-8477
Lee, Kyungwon(이경원) ORCID logo https://orcid.org/0000-0003-3788-2134
Jeong, Seok Hoon(정석훈) ORCID logo https://orcid.org/0000-0001-9290-897X
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