Acceleration and suppression of resistance development by antibiotic combinations

BMC Genomics

Research Article

Takaaki Horinouchi¹  Shingo Suzuki¹  Chikara Furusawa² 

[1] Laboratory for Multiscale Biosystem Dynamics, Quantitative Biology Center (QBiC), RIKEN, 6-2-3 Furuedai, 565-0874, Suita, Osaka, Japan;Laboratory for Multiscale Biosystem Dynamics, Quantitative Biology Center (QBiC), RIKEN, 6-2-3 Furuedai, 565-0874, Suita, Osaka, Japan;Universal Biology Institute, The University of Tokyo, 7-3-1 Hongo, 113-0033, Bunkyo-ku, Tokyo, Japan;

关键词: Laboratory evolution;    Escherichia coli;    Antibiotic resistance;   

DOI  :  10.1186/s12864-017-3718-2

 received in 2016-11-11, accepted in 2017-04-21,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe emergence and spread of antibiotic resistance in bacteria is becoming a global public health problem. Combination therapy, i.e., the simultaneous use of multiple antibiotics, is used for long-term treatment to suppress the emergence of resistant strains. However, the effect of the combinatorial use of multiple drugs on the development of resistance remains elusive, especially in a quantitative assessment.ResultsTo understand the evolutionary dynamics under combination therapy, we performed laboratory evolution of Escherichia coli under simultaneous addition of two-drug combinations. We demonstrated that simultaneous addition of a certain combinations of two drugs with collateral sensitivity to each other could suppress the acquisition of resistance to both drugs. Furthermore, we found that the combinatorial use of enoxacin, a DNA replication inhibitor, with Chloramphenicol can accelerate acquisition of resistance to Chloramphenicol. Genome resequencing analyses of the evolved strains suggested that the acceleration of resistance acquisition was caused by an increase of mutation frequency when enoxacin was added.ConclusionsIntegration of laboratory evolution and whole-genome sequencing enabled us to characterize the development of resistance in bacteria under combination therapy. These results provide a basis for rational selection of antibiotic combinations that suppress resistance development effectively.

【 授权许可】

CC BY   
© The Author(s). 2017