Insights into the evolutionary trajectories of fluoroquinolone resistance in Streptococcus pneumoniae----中国科学院微生物研究所

科研成果

论文题目:	Insights into the evolutionary trajectories of fluoroquinolone resistance in Streptococcus pneumoniae
作者:	Zhang Gang, Wang Chao, Sui Zhihai, and Feng Jie*.
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刊物名称:	J Antimicrob Chemother
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年份:	2015
影响因子:	4.984
论文下载:	http://jac.oxfordjournals.org/content/early/2015/05/31/jac.dkv134
摘要:	OBJECTIVES: Fluoroquinolone resistance in Streptococcus pneumoniae typically arises through specific site mutations, but dynamic variation of mutations in the resistance evolution and interaction among these mutations have not been clearly demonstrated. The objectives of this study were to investigate the dynamics of allele frequency in populations evolved under fluoroquinolone pressure and pervasive interactions among mutations present in the evolutionary trajectories. METHODS: Thirty-three evolved populations were obtained by serial passages in the presence of antibiotic pressure and these populations were sequenced by using the Paired-End Illumina method. Mutants that occurred in the evolutionary trajectories were constructed by transforming the parental strain with PCR fragments containing corresponding mutations. RESULTS: The number of target mutations increased progressively, consistent with phenotypic adaptation to moxifloxacin and levofloxacin. However, more mutations are required for high-level resistance to moxifloxacin than levofloxacin. Pervasive interactions, including positive epistasis between mutations, play a role in the evolutionary trajectories of resistance to the two drugs. Two mutations (R447C and P454S) in gyrB were identified to confer 2-fold increases in resistance to moxifloxacin and levofloxacin based on the background of the double mutant S81F/S79F in parC. Moreover, the dynamics of allele frequency in evolved populations was revealed and found to be directly correlated with the resistance levels of evolved populations. Clonal interference among alleles of mutations contributed to the molecular dynamics of resistance evolution. CONCLUSIONS: Our results provide novel insights into the evolutionary trajectories of resistance to fluoroquinolones and may serve as a theoretical basis for predicting resistance development and provide references for the clinical use of these drugs.