Format

Send to

Choose Destination
Yonsei Med J. 2015 Jul;56(4):928-34. doi: 10.3349/ymj.2015.56.4.928.

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

Author information

1
Department of Laboratory Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
2
Department of Dental Hygiene, Silla University, Busan, Korea.
3
Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Korea. kscpjsh@yuhs.ac.
4
Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Korea.

Abstract

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.

KEYWORDS:

Acinetobacter baumannii; armA gene; colistin; lipid A; pmrB gene

PMID:
26069113
PMCID:
PMC4479859
DOI:
10.3349/ymj.2015.56.4.928
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Yonsei University College of Medicine Icon for PubMed Central
Loading ...
Support Center