Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
PeerJ. 2023 Mar 22;11:e14969. doi: 10.7717/peerj.14969. eCollection 2023.
Ribosome-targeting antibiotics comprise over half of antibiotics used in medicine, but our fundamental knowledge of their binding sites is derived primarily from ribosome structures of non-pathogenic species. These include , and the archaean , as well as the commensal and sometimes pathogenic organism, . Advancements in electron cryomicroscopy have allowed for the determination of more ribosome structures from pathogenic bacteria, with each study highlighting species-specific differences that had not been observed in the non-pathogenic structures. These observed differences suggest that more novel ribosome structures, particularly from pathogens, are required for a more accurate understanding of the level of diversity of the entire bacterial ribosome, with the potential of leading to innovative advancements in antibiotic research. In this study, high accuracy covariance and hidden Markov models were used to annotate ribosomal RNA and protein sequences respectively from genomic sequence, allowing us to determine the underlying ribosomal sequence diversity using phylogenetic methods. This analysis provided evidence that the current non-pathogenic ribosome structures are not sufficient representatives of some pathogenic bacteria, such as , or of whole phyla such as Bacteroidota (Bacteroidetes).
核糖体靶向抗生素占医学中使用的抗生素的一半以上，但我们对其结合位点的基本认识主要来自于非病原物种的核糖体结构。这些包括、和古菌，以及共生且有时是病原的生物。电子冷冻显微镜技术的进步使得能够从病原细菌中确定更多的核糖体结构，每项研究都强调了在非病原结构中未观察到的物种特异性差异。这些观察到的差异表明，需要更多新型的核糖体结构，特别是来自病原体的核糖体结构，才能更准确地了解整个细菌核糖体的多样性程度，并有可能推动抗生素研究的创新进展。在这项研究中，高准确度协方差和隐马尔可夫模型分别用于注释来自基因组序列的核糖体 RNA 和蛋白质序列，使我们能够使用系统发育方法确定潜在的核糖体序列多样性。该分析提供的证据表明，目前的非病原核糖体结构不能充分代表某些病原细菌，如或整个门，如拟杆菌门（厚壁菌门）。
