Coexistence of SFO-1 and NDM-1 β-lactamase genes and fosfomycin resistance gene fosA3 in an Escherichia coli clinical isolate

Abstract

This study aims to characterize antimicrobial resistance and antimicrobial resistance genetic determinants of an Escherichia coli clinical isolate HD0149 from China in 2012. This strain displayed high-level resistance to cephalosporins, carbapenems, fluoroquinolones, aminoglycosides and fosfomycin. A range of antimicrobial resistance genes was detected responsible for its multiple antimicrobial resistances, involving the blaCMY-2, blaCTX-M-65, blaNDM-1, blaSFO-1, blaTEM-1, fosA3, rmtB, sul1 and sul2 genes. Four amino acid substitutions were detected in the quinolone resistance-determining regions (QRDRs) of GyrA (S83L and D87N), ParC (S80I) and ParE (S458A). Conjugation experiments revealed two multiresistance plasmids present in E. coli HD0149. The blaSFO-1 gene associated with blaNDM-1 gene was located in a 190 kb IncA/C plasmid and the blaCTX-M-65, fosA3 and rmtB genes were located in a 110 kb IncF plasmid. This is the first identification of the blaSFO-1 gene in an E. coli isolate and on a conjugative IncA/C plasmid. This may dramatically enhance the international prevalence and dissemination of blaSFO-1 among Enterobacteriaceae.

Pharmacodynamic Evaluation of the Potential Clinical Utility of Fosfomycin and Meropenem in Combination Therapy against KPC-2-Producing Klebsiella pneumoniae

“…Fosfomycin is being utilized more frequently, particularly against multidrug-resistant bacterial infections (42), although there are reported new cases of fosfomycin resistance development (43)(44)(45). Our study shows that fosfomycin dosing regimens are more likely to achieve the PTA against the MIC 90 of the combination, providing sufficient antimicrobial coverage even when the meropenem regimens at the maximum daily dosage fall short.…”

Fosfomycin

“…New subtypes, with similar structure, of the gene have been described (fosA2, fosA3, fosA4, and fosA5) (108)(109)(110). Cooccurrence in plasmids with bla CTX-M , bla NDM , bla KPC , bla OXA , bla CMY , bla AmpC , bla TEM , bla SHV , bla SFO-1 , gyrA, parC, parE, sul1, sul2, strA, strB, aac(6=)-Ib, aadA5, aphA6, tetA(A), mphA, floR, dfrA7, rmtB, and merA genes has been reported, conferring resistance to ␤-lactams, quinolones, aminoglycosides, macrolides, sulfonamides, and tetracyclines (75,80,(111)(112)(113)(114). The genes conferring resistance to fosfomycin could be transferred together with genes conferring resistance to other antibiotics in either the same or a conjugate plasmid (114).…”

IncA/C Plasmid Carrying bla NDM-1 , bla CMY-16 , and fosA3 in a Salmonella enterica Serovar Corvallis Strain Isolated from a Migratory Wild Bird in Germany

“…It has been suggested that the increasing prevalence of fosA3 is due to dissemination of the IncI1 and IncN plasmids rather than clonal expansion of specific strains (13,14). Recent reports from China described fosA3 on IncFII plasmids in S. enterica serovars Derby and Enteritidis from chickens purchased at the market in Hong Kong (15) and the copresence of both bla NDM-1 and fosA3 genes in a clinical E. coli isolate (16). Furthermore, the colocalization of the bla NDM-1 and fosA3 genes on IncA/C plasmids was demonstrated in E. coli and Citrobacter freundii clinical isolates in a report denouncing the high incidence and endemic spread of NDM-1-positive Enterobacteriaceae in the Henan Province of China (17).…”