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...
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MDPI AG
2020-08-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/9/9/534 |
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| author | Antonio Sorlozano-Puerto Isaac Lopez-Machado Maria Albertuz-Crespo Luis Javier Martinez-Gonzalez Jose Gutierrez-Fernandez |
| author_facet | Antonio Sorlozano-Puerto Isaac Lopez-Machado Maria Albertuz-Crespo Luis Javier Martinez-Gonzalez Jose Gutierrez-Fernandez |
| author_sort | Antonio Sorlozano-Puerto |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T16:54:17Z |
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| language | English |
| last_indexed | 2024-03-10T16:54:17Z |
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| spelling | doaj.art-c575f59cff094175aa2ae49476acfaf42023-11-20T11:13:34ZengMDPI AGAntibiotics2079-63822020-08-019953410.3390/antibiotics9090534Characterization of Fosfomycin and Nitrofurantoin Resistance Mechanisms in <i>Escherichia coli</i> Isolated in Clinical Urine SamplesAntonio Sorlozano-Puerto0Isaac Lopez-Machado1Maria Albertuz-Crespo2Luis Javier Martinez-Gonzalez3Jose Gutierrez-Fernandez4Department of Microbiology, School of Medicine and PhD Program in Clinical Medicine and Public Health, University of Granada-ibs, 18016 Granada, SpainDepartment of Microbiology, School of Medicine and PhD Program in Clinical Medicine and Public Health, University of Granada-ibs, 18016 Granada, SpainDepartment of Microbiology, School of Medicine and PhD Program in Clinical Medicine and Public Health, University of Granada-ibs, 18016 Granada, SpainPfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), 18016 Granada, SpainDepartment of Microbiology, School of Medicine and PhD Program in Clinical Medicine and Public Health, University of Granada-ibs, 18016 Granada, SpainFosfomycin 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.https://www.mdpi.com/2079-6382/9/9/534<i>Escherichia coli</i>fosfomycinnitrofurantoinantimicrobial resistance |
| spellingShingle | Antonio Sorlozano-Puerto Isaac Lopez-Machado Maria Albertuz-Crespo Luis Javier Martinez-Gonzalez Jose Gutierrez-Fernandez Characterization of Fosfomycin and Nitrofurantoin Resistance Mechanisms in <i>Escherichia coli</i> Isolated in Clinical Urine Samples Antibiotics <i>Escherichia coli</i> fosfomycin nitrofurantoin antimicrobial resistance |
| title | Characterization of Fosfomycin and Nitrofurantoin Resistance Mechanisms in <i>Escherichia coli</i> Isolated in Clinical Urine Samples |
| title_full | Characterization of Fosfomycin and Nitrofurantoin Resistance Mechanisms in <i>Escherichia coli</i> Isolated in Clinical Urine Samples |
| title_fullStr | Characterization of Fosfomycin and Nitrofurantoin Resistance Mechanisms in <i>Escherichia coli</i> Isolated in Clinical Urine Samples |
| title_full_unstemmed | Characterization of Fosfomycin and Nitrofurantoin Resistance Mechanisms in <i>Escherichia coli</i> Isolated in Clinical Urine Samples |
| title_short | Characterization of Fosfomycin and Nitrofurantoin Resistance Mechanisms in <i>Escherichia coli</i> Isolated in Clinical Urine Samples |
| title_sort | characterization of fosfomycin and nitrofurantoin resistance mechanisms in i escherichia coli i isolated in clinical urine samples |
| topic | <i>Escherichia coli</i> fosfomycin nitrofurantoin antimicrobial resistance |
| url | https://www.mdpi.com/2079-6382/9/9/534 |
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