Adaptive modulation of antibiotic resistance through intragenomic coevolution

TY - JOUR

T1 - Adaptive modulation of antibiotic resistance through intragenomic coevolution

AU - Bottery, Michael John

AU - Wood, Andrew James

AU - Brockhurst, Michael Alan

N1 - © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Bacteria gain antibiotic resistance genes by horizontal acquisition of mobile genetic elements (MGEs) from other lineages. Newly acquired MGEs are often poorly adapted causing intragenomic conflicts; these are resolved by either compensatory adaptation - of the chromosome or the MGE - or reciprocal coadaptation. The footprints of such intragenomic coevolution are present in bacterial genomes, suggesting an important role promoting genomic integration of horizontally acquired genes, but direct experimental evidence of the process is limited. Here we show adaptive modulation of tetracycline resistance via intragenomic coevolution between Escherichia coli and the multidrug resistant plasmid RK2. Tetracycline treatments, including monotherapy or combination therapies with ampicillin, favoured de novo chromosomal resistance mutations coupled with mutations on RK2 impairing the plasmid-encoded tetracycline efflux pump. These mutations together provided increased tetracycline resistance at reduced cost. Additionally, the chromosomal resistance mutations conferred cross-resistance to chloramphenicol. Reciprocal coadaptation was not observed under ampicillin-only or no antibiotic selection. Intragenomic coevolution can create genomes comprising multiple replicons that together provide high-level, low-cost resistance, but the resulting co-dependence may limit the spread of coadapted MGEs to other lineages.

AB - Bacteria gain antibiotic resistance genes by horizontal acquisition of mobile genetic elements (MGEs) from other lineages. Newly acquired MGEs are often poorly adapted causing intragenomic conflicts; these are resolved by either compensatory adaptation - of the chromosome or the MGE - or reciprocal coadaptation. The footprints of such intragenomic coevolution are present in bacterial genomes, suggesting an important role promoting genomic integration of horizontally acquired genes, but direct experimental evidence of the process is limited. Here we show adaptive modulation of tetracycline resistance via intragenomic coevolution between Escherichia coli and the multidrug resistant plasmid RK2. Tetracycline treatments, including monotherapy or combination therapies with ampicillin, favoured de novo chromosomal resistance mutations coupled with mutations on RK2 impairing the plasmid-encoded tetracycline efflux pump. These mutations together provided increased tetracycline resistance at reduced cost. Additionally, the chromosomal resistance mutations conferred cross-resistance to chloramphenicol. Reciprocal coadaptation was not observed under ampicillin-only or no antibiotic selection. Intragenomic coevolution can create genomes comprising multiple replicons that together provide high-level, low-cost resistance, but the resulting co-dependence may limit the spread of coadapted MGEs to other lineages.

UR - http://www.scopus.com/inward/record.url?scp=85031903469&partnerID=8YFLogxK

U2 - 10.1038/s41559-017-0242-3

DO - 10.1038/s41559-017-0242-3

M3 - Article

C2 - 28890939

SN - 2397-334X

VL - 1

SP - 1364

EP - 1369

JO - Nature Ecology and Evolution

JF - Nature Ecology and Evolution

IS - 9

ER -