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BioMed Research International
Volume 2017, Article ID 5470241, 8 pages
Research Article

Mechanism of Reduced Susceptibility to Fosfomycin in Escherichia coli Clinical Isolates

1Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan
2Department of Clinical Laboratory, NTT East Sapporo Hospital, Chuo-ku, Sapporo 060-0061, Japan

Correspondence should be addressed to Shin-ichi Yokota;

Received 15 July 2016; Revised 22 December 2016; Accepted 27 December 2016; Published 19 January 2017

Academic Editor: Yun-Peng Chao

Copyright © 2017 Yasuo Ohkoshi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


In recent years, multidrug resistance of Escherichia coli has become a serious problem. However, resistance to fosfomycin (FOM) has been low. We screened E. coli clinical isolates with reduced susceptibility to FOM and characterized molecular mechanisms of resistance and reduced susceptibility of these strains. Ten strains showing reduced FOM susceptibility (MIC ≥ 8 μg/mL) in 211 clinical isolates were found and examined. Acquisition of genes encoding FOM-modifying enzyme genes (fos genes) and mutations in murA that underlie high resistance to FOM were not observed. We examined ability of FOM incorporation via glucose-6-phosphate (G6P) transporter and sn-glycerol-3-phosphate transporter. In ten strains, nine showed lack of growth on M9 minimum salt agar supplemented with G6P. Eight of the ten strains showed fluctuated induction by G6P of uhpT that encodes G6P transporter expression. Nucleotide sequences of the uhpT, uhpA, glpT, ptsI, and cyaA shared several deletions and amino acid mutations in the nine strains with lack of growth on G6P-supplemented M9 agar. In conclusion, reduction of uhpT function is largely responsible for the reduced sensitivity to FOM in clinical isolates that have not acquired FOM-modifying genes or mutations in murA. However, there are a few strains whose mechanisms of reduced susceptibility to FOM are still unclear.