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: Bakhtiyar Mahmood (Author), Ana Paunkov (Author), Malgorzata Kupc (Author), Katalin Burián (Author), Elisabeth Nagy (Author), David Leitsch (Author), József Sóki (Author)
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Published: MDPI AG, 2024-02-01T00:00:00Z.
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001 doaj_8a72e60a3cd042b09b69d13b8e800ca5
042 |a dc 
100 1 0 |a Bakhtiyar Mahmood  |e author 
700 1 0 |a Ana Paunkov  |e author 
700 1 0 |a Malgorzata Kupc  |e author 
700 1 0 |a Katalin Burián  |e author 
700 1 0 |a Elisabeth Nagy  |e author 
700 1 0 |a David Leitsch  |e author 
700 1 0 |a József Sóki  |e author 
245 0 0 |a Proteomics-Based RT-qPCR and Functional Analysis of 18 Genes in Metronidazole Resistance of <i>Bacteroides fragilis</i> 
260 |b MDPI AG,   |c 2024-02-01T00:00:00Z. 
500 |a 10.3390/antibiotics13030207 
500 |a 2079-6382 
520 |a 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. 
546 |a EN 
690 |a <i>Bacteroides</i> 
690 |a metronidazole 
690 |a <i>nim</i> 
690 |a resistance mechanism 
690 |a RT-qPCR 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Antibiotics, Vol 13, Iss 3, p 207 (2024) 
787 0 |n https://www.mdpi.com/2079-6382/13/3/207 
787 0 |n https://doaj.org/toc/2079-6382 
856 4 1 |u https://doaj.org/article/8a72e60a3cd042b09b69d13b8e800ca5  |z Connect to this object online.