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一种测定食菌蛭弧菌抗生素敏感性的新方法揭示了一种依赖二氢叶酸还原酶的天然甲氧苄啶抗性。

A novel method to determine antibiotic sensitivity in Bdellovibrio bacteriovorus reveals a DHFR-dependent natural trimethoprim resistance.

作者信息

Marine Emanuele, Milner David Stephen, Lambert Carey, Sockett Renee Elizabeth, Pos Klaas Martinus

机构信息

Institute of Biochemistry, Goethe-University Frankfurt, D-60438, Frankfurt am Main, Germany.

Institute of Immunology and Microbiology, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK.

出版信息

Sci Rep. 2020 Mar 24;10(1):5315. doi: 10.1038/s41598-020-62014-x.

DOI:10.1038/s41598-020-62014-x
PMID:32210253
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7093396/
Abstract

Bdellovibrio bacteriovorus is a small Gram-negative bacterium and an obligate predator of other Gram-negative bacteria. Prey resistance to B. bacteriovorus attack is rare and transient. This consideration together with its safety and low immunogenicity makes B. bacteriovorus a valid alternative to antibiotics, especially in the treatment of multidrug resistant pathogens. In this study we developed a novel technique to estimate B. bacteriovorus sensitivity against antibiotics in order to make feasible the development and testing of co-therapies with antibiotics that would increase its antimicrobial efficacy and at the same time reduce the development of drug resistance. Results from tests performed with this technique show that among all tested antibiotics, trimethoprim has the lowest antimicrobial effect on B. bacteriovorus. Additional experiments revealed that the mechanism of trimethoprim resistance in B. bacteriovorus depends on the low affinity of this compound for the B. bacteriovorus dihydrofolate reductase (Bd DHFR).

摘要

食菌蛭弧菌是一种革兰氏阴性小细菌,是其他革兰氏阴性细菌的专性捕食者。猎物对食菌蛭弧菌攻击的抗性罕见且短暂。鉴于此,以及其安全性和低免疫原性,食菌蛭弧菌成为抗生素的有效替代品,尤其是在治疗多重耐药病原体方面。在本研究中,我们开发了一种新技术来评估食菌蛭弧菌对抗生素的敏感性,以便使与抗生素联合治疗的开发和测试变得可行,这将提高其抗菌效果,同时减少耐药性的产生。用该技术进行测试的结果表明,在所有测试的抗生素中,甲氧苄啶对食菌蛭弧菌的抗菌作用最低。进一步的实验表明,食菌蛭弧菌对甲氧苄啶的耐药机制取决于该化合物对食菌蛭弧菌二氢叶酸还原酶(Bd DHFR)的低亲和力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9dc/7093396/2467055a89d5/41598_2020_62014_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9dc/7093396/0856c3d97605/41598_2020_62014_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9dc/7093396/912029ca67b4/41598_2020_62014_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9dc/7093396/122b2bb3c987/41598_2020_62014_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9dc/7093396/8f58bc1515fd/41598_2020_62014_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9dc/7093396/fdb90d9a9f2f/41598_2020_62014_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9dc/7093396/2467055a89d5/41598_2020_62014_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9dc/7093396/0856c3d97605/41598_2020_62014_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9dc/7093396/912029ca67b4/41598_2020_62014_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9dc/7093396/122b2bb3c987/41598_2020_62014_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9dc/7093396/8f58bc1515fd/41598_2020_62014_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9dc/7093396/fdb90d9a9f2f/41598_2020_62014_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9dc/7093396/2467055a89d5/41598_2020_62014_Fig6_HTML.jpg

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