AmpI Functions as an Iron Exporter To Alleviate β-Lactam-Mediated Reactive Oxygen Species Stress in Stenotrophomonas maltophilia
Copyright © 2019 American Society for Microbiology..
Stenotrophomonas maltophilia is an organism with a remarkable capacity for drug resistance with several antibiotic resistance determinants in its genome. S. maltophilia genome codes for L1 and L2, responsible for intrinsic β-lactam resistance. The Smlt3721 gene (denoted ampI), located downstream of the L2 gene, encodes an inner membrane protein. The existence of an L2 gene-ampI operon was verified by reverse transcription-PCR (RT-PCR). For aerobically grown S. maltophilia KJ, inactivation of ampI downregulated siderophore synthesis and iron acquisition systems and upregulated the iron storage system, as demonstrated by a transcriptome assay, suggesting that AmpI is involved in iron homeostasis. Compared with the wild-type KJ, an ampI mutant had an elevated intracellular iron level, as revealed by inductively coupled plasma mass spectrometry (ICP-MS) analysis, and increased sensitivity to H2O2, verifying the role of AmpI as an iron exporter. The β-lactam stress increased the intracellular reactive oxygen species (ROS) level and induced the expression of the L1 gene and L2 gene-ampI operon. Compared to its own parental strain, the ampI mutant had reduced growth in β-lactam-containing medium, and the ampI mutant viability was improved after complementation with plasmid pAmpI in either a β-lactamase-positive or β-lactamase-negative genetic background. Collectively, upon challenge with β-lactam, the inducibly expressed L1 and L2 β-lactamases contribute to β-lactam resistance by hydrolyzing β-lactam. AmpI functions as an iron exporter participating in rapidly weakening β-lactam-mediated ROS toxicity. The L1 gene and L2 gene-ampI operon enable S. maltophilia to effectively cope with β-lactam-induced stress.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:63 |
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| Enthalten in: |
Antimicrobial agents and chemotherapy - 63(2019), 4 vom: 15. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Yi-Wei [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.02.2020 Date Revised 09.03.2020 published: Electronic-Print Citation Status MEDLINE |
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| doi: |
10.1128/AAC.02467-18 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM293711887 |
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| 245 | 1 | 0 | |a AmpI Functions as an Iron Exporter To Alleviate β-Lactam-Mediated Reactive Oxygen Species Stress in Stenotrophomonas maltophilia |
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| 520 | |a Copyright © 2019 American Society for Microbiology. | ||
| 520 | |a Stenotrophomonas maltophilia is an organism with a remarkable capacity for drug resistance with several antibiotic resistance determinants in its genome. S. maltophilia genome codes for L1 and L2, responsible for intrinsic β-lactam resistance. The Smlt3721 gene (denoted ampI), located downstream of the L2 gene, encodes an inner membrane protein. The existence of an L2 gene-ampI operon was verified by reverse transcription-PCR (RT-PCR). For aerobically grown S. maltophilia KJ, inactivation of ampI downregulated siderophore synthesis and iron acquisition systems and upregulated the iron storage system, as demonstrated by a transcriptome assay, suggesting that AmpI is involved in iron homeostasis. Compared with the wild-type KJ, an ampI mutant had an elevated intracellular iron level, as revealed by inductively coupled plasma mass spectrometry (ICP-MS) analysis, and increased sensitivity to H2O2, verifying the role of AmpI as an iron exporter. The β-lactam stress increased the intracellular reactive oxygen species (ROS) level and induced the expression of the L1 gene and L2 gene-ampI operon. Compared to its own parental strain, the ampI mutant had reduced growth in β-lactam-containing medium, and the ampI mutant viability was improved after complementation with plasmid pAmpI in either a β-lactamase-positive or β-lactamase-negative genetic background. Collectively, upon challenge with β-lactam, the inducibly expressed L1 and L2 β-lactamases contribute to β-lactam resistance by hydrolyzing β-lactam. AmpI functions as an iron exporter participating in rapidly weakening β-lactam-mediated ROS toxicity. The L1 gene and L2 gene-ampI operon enable S. maltophilia to effectively cope with β-lactam-induced stress | ||
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| 700 | 1 | |a Yang, Tsuey-Ching |e verfasserin |4 aut | |
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