Reassessment of the genetic basis of natural rifampin resistance in the genus Rickettsia

IF 3.9 3区 生物学 Q2 MICROBIOLOGY MicrobiologyOpen Pub Date : 2024-07-31 DOI:10.1002/mbo3.1431
Julien Amoros, Noor Fattar, Marie Buysse, Meriem Louni, Joanne Bertaux, Didier Bouchon, Olivier Duron
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Abstract

Rickettsia, a genus of obligate intracellular bacteria, includes species that cause significant human diseases. This study challenges previous claims that the Leucine-973 residue in the RNA polymerase beta subunit is the primary determinant of rifampin resistance in Rickettsia. We investigated a previously untested Rickettsia species, R. lusitaniae, from the Transitional group and found it susceptible to rifampin, despite possessing the Leu-973 residue. Interestingly, we observed the conservation of this residue in several rifampin-susceptible species across most Rickettsia phylogenetic groups. Comparative genomics revealed potential alternative resistance mechanisms, including additional amino acid variants that could hinder rifampin binding and genes that could facilitate rifampin detoxification through efflux pumps. Importantly, the evolutionary history of Rickettsia genomes indicates that the emergence of natural rifampin resistance is phylogenetically constrained within the genus, originating from ancient genetic features shared among a unique set of closely related Rickettsia species. Phylogenetic patterns appear to be the most reliable predictors of natural rifampin resistance, which is confined to a distinct monophyletic subclade known as Massiliae. The distinctive features of the RNA polymerase beta subunit in certain untested Rickettsia species suggest that R. raoultii, R. amblyommatis, R. gravesii, and R. kotlanii may also be naturally rifampin-resistant species.

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重新评估立克次体属天然利福平抗药性的遗传基础。
立克次体(Rickettsia)是一种必须在细胞内生存的细菌,其中一些种类可导致严重的人类疾病。本研究质疑了以前的说法,即 RNA 聚合酶 beta 亚基中的亮氨酸-973 残基是立克次体对利福平产生耐药性的主要决定因素。我们研究了一种以前未检测过的立克次体,即过渡群中的R. lusitaniae,发现它对利福平敏感,尽管存在亮氨酸-973残基。有趣的是,在大多数立克次体系统发育群中,我们观察到几个对利福平敏感的物种都保留了这个残基。比较基因组学揭示了潜在的替代抗性机制,包括可能阻碍利福平结合的其他氨基酸变体和通过外排泵促进利福平解毒的基因。重要的是,立克次体基因组的进化史表明,天然利福平抗药性的出现在立克次体属内部受到系统发育的限制,它源于一系列独特的近缘立克次体物种之间共享的古老遗传特征。系统发育模式似乎是天然利福平抗药性最可靠的预测因素,天然利福平抗药性仅限于一个独特的单系亚支系,即Massiliae。某些未经检测的立克次体RNA聚合酶β亚基的独特特征表明,R. raoultii、R. amblyommatis、R. gravesii和R. kotlanii也可能是具有天然利福平抗药性的物种。
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来源期刊
MicrobiologyOpen
MicrobiologyOpen MICROBIOLOGY-
CiteScore
8.00
自引率
0.00%
发文量
78
审稿时长
20 weeks
期刊介绍: MicrobiologyOpen is a peer reviewed, fully open access, broad-scope, and interdisciplinary journal delivering rapid decisions and fast publication of microbial science, a field which is undergoing a profound and exciting evolution in this post-genomic era. The journal aims to serve the research community by providing a vehicle for authors wishing to publish quality research in both fundamental and applied microbiology. Our goal is to publish articles that stimulate discussion and debate, as well as add to our knowledge base and further the understanding of microbial interactions and microbial processes. MicrobiologyOpen gives prompt and equal consideration to articles reporting theoretical, experimental, applied, and descriptive work in all aspects of bacteriology, virology, mycology and protistology, including, but not limited to: - agriculture - antimicrobial resistance - astrobiology - biochemistry - biotechnology - cell and molecular biology - clinical microbiology - computational, systems, and synthetic microbiology - environmental science - evolutionary biology, ecology, and systematics - food science and technology - genetics and genomics - geobiology and earth science - host-microbe interactions - infectious diseases - natural products discovery - pharmaceutical and medicinal chemistry - physiology - plant pathology - veterinary microbiology We will consider submissions across unicellular and cell-cluster organisms: prokaryotes (bacteria, archaea) and eukaryotes (fungi, protists, microalgae, lichens), as well as viruses and prions infecting or interacting with microorganisms, plants and animals, including genetic, biochemical, biophysical, bioinformatic and structural analyses. The journal features Original Articles (including full Research articles, Method articles, and Short Communications), Commentaries, Reviews, and Editorials. Original papers must report well-conducted research with conclusions supported by the data presented in the article. We also support confirmatory research and aim to work with authors to meet reviewer expectations. MicrobiologyOpen publishes articles submitted directly to the journal and those referred from other Wiley journals.
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