Single-Step Selection of Drug Resistant Acinetobacter baylyi ADP1 Mutants Reveals a Functional Redundancy in the Recruitment of Multidrug Efflux Systems

被引:16
作者
Brzoska, Anthony J. [1 ,2 ,3 ]
Hassan, Karl A. [2 ]
de Leon, Ellen J. [4 ]
Paulsen, Ian T. [2 ]
Lewis, Peter J. [3 ]
机构
[1] Univ Sydney, Sch Biol Sci, Sydney, NSW 2006, Australia
[2] Macquarie Univ, Dept Chem & Biomol Sci, Sydney, NSW 2109, Australia
[3] Univ Newcastle, Sch Environm & Life Sci, Callaghan, NSW 2308, Australia
[4] Univ Queensland, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld, Australia
基金
英国医学研究理事会;
关键词
MESSENGER-RNA; BAUMANNII; PUMP; SUSCEPTIBILITY; TRANSPORTERS; ANTIBIOTICS; EXPRESSION; STABILITY; ADEIJK;
D O I
10.1371/journal.pone.0056090
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Members of the genus Acinetobacter have been the focus recent attention due to both their clinical significance and application to molecular biology. The soil commensal bacterium Acinetobacter baylyi ADP1 has been proposed as a model system for molecular and genetic studies, whereas in a clinical environment, Acinetobacter spp. are of increasing importance due to their propensity to cause serious and intractable systemic infections. Clinically, a major factor in the success of Acinetobacter spp. as opportunistic pathogens can be attributed to their ability to rapidly evolve resistance to common antimicrobial compounds. Whole genome sequencing of clinical and environmental Acinetobacter spp. isolates has revealed the presence of numerous multidrug transporters within the core and accessory genomes, suggesting that efflux is an important host defense response in this genus. In this work, we used the drug-susceptible organism A. baylyi ADP1 as a model for studies into the evolution of efflux mediated resistance in genus Acinetobacter, due to the high level of conservation of efflux determinants across four diverse Acinetobacter strains, including clinical isolates. A single exposure of therapeutic concentrations of chloramphenicol to populations of A. baylyi ADP1 cells produced five individual colonies displaying multidrug resistance. The major facilitator superfamily pump craA was upregulated in one mutant strain, whereas the resistance nodulation division pump adeJ was upregulated in the remaining four. Within the adeJ upregulated population, two different levels of adeJ mRNA transcription were observed, suggesting at least three separate mutations were selected after single-step exposure to chloramphenicol. In the craA upregulated strain, a T to G substitution 12 nt upstream of the craA translation initiation codon was observed. Subsequent mRNA stability analyses using this strain revealed that the half-life of mutant craA mRNA was significantly greater than that of wild-type craA mRNA.
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页数:11
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