Proteomics-Based RT-qPCR and Functional Analysis of 18 Genes in Metronidazole Resistance of <i>Bacteroides fragilis</i>
Previously, we reported that metronidazole MICs are not dependent on the expression levels of <i>nim</i> genes in <i>B. fragilis</i> strains and we compared the proteomes of metronidazole-resistant laboratory <i>B. fragilis</i> strains to those of their susceptibl...
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| Main Authors: | , , , , , , |
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| Format: | Book |
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MDPI AG,
2024-02-01T00:00:00Z.
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| Summary: | Previously, we reported that metronidazole MICs are not dependent on the expression levels of <i>nim</i> genes in <i>B. fragilis</i> strains and we compared the proteomes of metronidazole-resistant laboratory <i>B. fragilis</i> strains to those of their susceptible parent strains. Here, we used RT-qPCR to correlate the expression levels of 18 candidate genes in a panel of selected, clinical <i>nim</i> gene-positive and -negative <i>B. fragilis</i> strains to their metronidazole MICs. Metronidazole MICs were correlated with the expression of certain tested genes. Specifically, lactate dehydrogenase expression correlated positively, whereas cytochrome fumarate reductase/succinate dehydrogenase, malate dehydrogenase, phosphoglycerate kinase redox and <i>gat</i> (GCN5-like acetyltransferase), and <i>relA</i> (stringent response) regulatory gene expressions correlated negatively with metronidazole MICs. This result provides evidence for the involvement of carbohydrate catabolic enzymes in metronidazole resistance in <i>B. fragilis</i>. This result was supported by direct substrate utilization tests. However, the exact roles of these genes/proteins should be determined in deletion-complementation tests. Moreover, the exact redox cofactor(s) participating in metronidazole activation need to be identified. |
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| Item Description: | 10.3390/antibiotics13030207 2079-6382 |