Tags

Type your tag names separated by a space and hit enter

Modifications in the pmrB gene are the primary mechanism for the development of chromosomally encoded resistance to polymyxins in uropathogenic Escherichia coli.
J Antimicrob Chemother. 2017 10 01; 72(10):2729-2736.JA

Abstract

Objectives

Polymyxins remain one of the last-resort drugs to treat infections caused by MDR Gram-negative pathogens. Here, we determined the mechanisms by which chromosomally encoded resistance to colistin and polymyxin B can arise in the MDR uropathogenic Escherichia coli ST131 reference strain EC958.

Methods

Two complementary approaches, saturated transposon mutagenesis and spontaneous mutation induction with high concentrations of colistin and polymyxin B, were employed to select for mutations associated with resistance to polymyxins. Mutants were identified using transposon-directed insertion-site sequencing or Illumina WGS. A resistance phenotype was confirmed by MIC and further investigated using RT-PCR. Competitive growth assays were used to measure fitness cost.

Results

A transposon insertion at nucleotide 41 of the pmrB gene (EC958pmrB41-Tn5) enhanced its transcript level, resulting in a 64- and 32-fold increased MIC of colistin and polymyxin B, respectively. Three spontaneous mutations, also located within the pmrB gene, conferred resistance to both colistin and polymyxin B with a corresponding increase in transcription of the pmrCAB genes. All three mutations incurred a fitness cost in the absence of colistin and polymyxin B.

Conclusions

This study identified the pmrB gene as the main chromosomal target for induction of colistin and polymyxin B resistance in E. coli.

Authors+Show Affiliations

School of Chemistry & Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia. Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia.School of Chemistry & Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia. Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia.School of Chemistry & Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia. Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia.School of Chemistry & Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia. Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia. Australian Centre for Ecogenomics, The University of Queensland, Brisbane, Queensland, Australia.Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala, Lumpur, Malaysia.Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala, Lumpur, Malaysia.Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala, Lumpur, Malaysia.Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala, Lumpur, Malaysia.School of Chemistry & Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia. Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia.School of Chemistry & Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia. Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia.Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia. The University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Queensland, Australia.School of Chemistry & Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia. Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia. Australian Centre for Ecogenomics, The University of Queensland, Brisbane, Queensland, Australia.School of Chemistry & Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia. Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29091192

Citation

Phan, Minh-Duy, et al. "Modifications in the pmrB Gene Are the Primary Mechanism for the Development of Chromosomally Encoded Resistance to Polymyxins in Uropathogenic Escherichia Coli." The Journal of Antimicrobial Chemotherapy, vol. 72, no. 10, 2017, pp. 2729-2736.
Phan MD, Nhu NTK, Achard MES, et al. Modifications in the pmrB gene are the primary mechanism for the development of chromosomally encoded resistance to polymyxins in uropathogenic Escherichia coli. J Antimicrob Chemother. 2017;72(10):2729-2736.
Phan, M. D., Nhu, N. T. K., Achard, M. E. S., Forde, B. M., Hong, K. W., Chong, T. M., Yin, W. F., Chan, K. G., West, N. P., Walker, M. J., Paterson, D. L., Beatson, S. A., & Schembri, M. A. (2017). Modifications in the pmrB gene are the primary mechanism for the development of chromosomally encoded resistance to polymyxins in uropathogenic Escherichia coli. The Journal of Antimicrobial Chemotherapy, 72(10), 2729-2736. https://doi.org/10.1093/jac/dkx204
Phan MD, et al. Modifications in the pmrB Gene Are the Primary Mechanism for the Development of Chromosomally Encoded Resistance to Polymyxins in Uropathogenic Escherichia Coli. J Antimicrob Chemother. 2017 10 1;72(10):2729-2736. PubMed PMID: 29091192.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modifications in the pmrB gene are the primary mechanism for the development of chromosomally encoded resistance to polymyxins in uropathogenic Escherichia coli. AU - Phan,Minh-Duy, AU - Nhu,Nguyen Thi Khanh, AU - Achard,Maud E S, AU - Forde,Brian M, AU - Hong,Kar Wai, AU - Chong,Teik Min, AU - Yin,Wai-Fong, AU - Chan,Kok-Gan, AU - West,Nicholas P, AU - Walker,Mark J, AU - Paterson,David L, AU - Beatson,Scott A, AU - Schembri,Mark A, PY - 2017/03/20/received PY - 2017/05/26/accepted PY - 2017/11/2/entrez PY - 2017/11/2/pubmed PY - 2018/6/14/medline SP - 2729 EP - 2736 JF - The Journal of antimicrobial chemotherapy JO - J. Antimicrob. Chemother. VL - 72 IS - 10 N2 - Objectives: Polymyxins remain one of the last-resort drugs to treat infections caused by MDR Gram-negative pathogens. Here, we determined the mechanisms by which chromosomally encoded resistance to colistin and polymyxin B can arise in the MDR uropathogenic Escherichia coli ST131 reference strain EC958. Methods: Two complementary approaches, saturated transposon mutagenesis and spontaneous mutation induction with high concentrations of colistin and polymyxin B, were employed to select for mutations associated with resistance to polymyxins. Mutants were identified using transposon-directed insertion-site sequencing or Illumina WGS. A resistance phenotype was confirmed by MIC and further investigated using RT-PCR. Competitive growth assays were used to measure fitness cost. Results: A transposon insertion at nucleotide 41 of the pmrB gene (EC958pmrB41-Tn5) enhanced its transcript level, resulting in a 64- and 32-fold increased MIC of colistin and polymyxin B, respectively. Three spontaneous mutations, also located within the pmrB gene, conferred resistance to both colistin and polymyxin B with a corresponding increase in transcription of the pmrCAB genes. All three mutations incurred a fitness cost in the absence of colistin and polymyxin B. Conclusions: This study identified the pmrB gene as the main chromosomal target for induction of colistin and polymyxin B resistance in E. coli. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/29091192/Modifications_in_the_pmrB_gene_are_the_primary_mechanism_for_the_development_of_chromosomally_encoded_resistance_to_polymyxins_in_uropathogenic_Escherichia_coli_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkx204 DB - PRIME DP - Unbound Medicine ER -