AUTHOR=Wang Mingyu , Wang Wenjia , Niu Yu , Liu Ting , Li Ling , Zhang Mengge , Li Ziyun , Su Wenya , Liu Fangyue , Zhang Xuhua , Xu Hai 

TITLE=A Clinical Extensively-Drug Resistant (XDR) Escherichia coli and Role of Its β-Lactamase Genes

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.590357

DOI=10.3389/fmicb.2020.590357

ISSN=1664-302X

ABSTRACT=<p>An extensively-drug resistant (XDR) <italic>Escherichia coli</italic> W60 was isolated from the urine sample of a patient. The genetic basis for its XDR phenotype was investigated, particularly the basis for its resistance toward β-lactam/BLI (β-Lactamase Inhibitor) combinations. Following determination of the XDR phenotype, third generation genomic sequencing was performed to identify genetic structures in <italic>E. coli</italic> W60. Further cloning analysis was performed to identify determinants of β-lactam/BLI combination resistance. It was found that <italic>E. coli</italic> W60 is resistant to nearly all of the tested antibiotics including all commonly used β-lactam/BLI combinations. Analysis of the genomic structures in <italic>E. coli</italic> W60 showed two novel transferable plasmids are responsible for the resistance phenotypes. Further genetic analysis showed <italic>bla</italic><sub>NDM–5</sub> leads to high resistance to β-lactam/BLI combinations, which was enhanced by co-expressing <italic>ble</italic><sub>MBL</sub>. pECW602 harbors a truncated <italic>bla</italic><sub>TEM</sub> that is not functional due to the loss of the N-terminal signal peptide coding region. Research performed in this work leads to several significant conclusions: the XDR phenotype of <italic>E. coli</italic> W60 can be attributed to the presence of transferable multidrug resistance plasmids; NDM-5 confers high resistance to β-lactam/BLI combinations; co-expression of <italic>ble</italic><sub>MBL</sub> enhances resistance caused by NDM-5; the signal peptides of TEM type β-lactamases are essential for their secretion and function. Findings of this work show the danger of transferable multidrug resistance plasmids and metallo-β-lactamases, both of which should be given more attention in the analysis and treatment of multidrug resistant pathogens.</p>