Characterization of Fosfomycin and Nitrofurantoin Resistance Mechanisms in <i>Escherichia coli</i> Isolated in Clinical Urine Samples
Fosfomycin and nitrofurantoin are antibiotics of choice to orally treat non-complicated urinary tract infections (UTIs) of community origin because they remain active against bacteria resistant to other antibiotics. However, epidemiologic surveillance studies have detected a reduced susceptibility t...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Book |
| Published: |
MDPI AG,
2020-08-01T00:00:00Z.
|
| Subjects: | |
| Online Access: | Connect to this object online. |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Fosfomycin and nitrofurantoin are antibiotics of choice to orally treat non-complicated urinary tract infections (UTIs) of community origin because they remain active against bacteria resistant to other antibiotics. However, epidemiologic surveillance studies have detected a reduced susceptibility to these drugs. The objective of this study was to determine possible mechanisms of resistance to these antibiotics in clinical isolates of fosfomycin- and/or nitrofurantoin-resistant UTI-producing <i>Escherichia coli</i>. We amplified and sequenced <i>murA</i>, <i>glpT</i>, <i>uhpT</i>, <i>uhpA</i>, <i>ptsI</i>, <i>cyaA</i>, <i>nfsA</i>, <i>nfsB</i>, and <i>ribE</i> genes, and screened plasmid-borne fosfomycin-resistance genes <i>fosA3</i>, <i>fosA4</i>, <i>fosA5</i>, <i>fosA6</i>, and <i>fosC2</i> and nitrofurantoin-resistance genes <i>oqxA</i> and <i>oqxB</i> by polymerase chain reaction. Among 29 isolates studied, 22 were resistant to fosfomycin due to deletion of <i>uhpT</i> and/or <i>uhpA</i> genes, and 2 also possessed the <i>fosA3</i> gene. Some modifications detected in sequences of NfsA (His11Tyr, Ser33Arg, Gln67Leu, Cys80Arg, Gly126Arg, Gly154Glu, Arg203Cys), NfsB (Gln44His, Phe84Ser, Arg107Cys, Gly192Ser, Arg207His), and RibE (Pro55His), and the production of truncated NfsA (Gln67 and Gln147) and NfsB (Glu54), were associated with nitrofurantoin resistance in 15/29 isolates; however, the presence of <i>oqxAB</i> plasmid genes was not detected in any isolate. Resistance to fosfomycin was associated with the absence of transporter UhpT expression and/or the presence of antibiotic-modifying enzymes encoded by <i>fosA3</i> plasmid-mediated gene. Resistance to nitrofurantoin was associated with modifications of NfsA, NfsB, and RibE proteins. The emergence and spread of these resistance mechanisms, including transferable resistance, could compromise the future usefulness of fosfomycin and nitrofurantoin against UTIs. Furthermore, knowledge of the genetic mechanisms underlying resistance may lead to rapid DNA-based testing for resistance. |
|---|---|
| Item Description: | 10.3390/antibiotics9090534 2079-6382 |