Tetz George, Kardava Kristina, Vecherkovskaya Maria, Khodadadi-Jamayran Alireza, Tsirigos Aristotelis, Tetz Victor
Human Microbiology Institute, New York, NY, 10014, USA.
Tetz Labs, New York, NY, 10014, USA.
Microb Cell Fact. 2025 Jan 3;24(1):1. doi: 10.1186/s12934-024-02637-1.
Our previous studies revealed the existence of a Universal Receptive System that regulates interactions between cells and their environment. This system is composed of DNA- and RNA-based Teazeled receptors (TezRs) found on the surface of prokaryotic and eukaryotic cells, as well as integrases and recombinases. In the current study, we aimed to provide further insight into the regulatory role of TezR and its loss in Staphylococcus aureus gene transcription. To this end, transcriptomic analysis of S. aureus MSSA VT209 was performed following the destruction of TezRs. Bacterial RNA samples were extracted from nuclease-treated and untreated S. aureus MSSA VT209. After destruction of the DNA-based-, RNA-, or combined DNA- and RNA-based TezRs of S. aureus, 103, 150, and 93 genes were significantly differently expressed, respectively. The analysis revealed differential clustering of gene expression following the loss of different TezRs, highlighting individual cellular responses following the loss of DNA- and RNA-based TezRs. KEGG pathway gene enrichment analysis revealed that the most upregulated pathways following TezR inactivation included those related to energy metabolism, cell wall metabolism, and secretion systems. Some of the genetic pathways were related to the inhibition of biofilm formation and increased antibiotic resistance, and we confirmed this at the phenotypic level using in vitro studies. The results of this study add another line of evidence that the Universal Receptive System plays an important role in cell regulation, including cell responses to the environmental factors of clinically important pathogens, and that nucleic acid-based TezRs are functionally active parts of the extrabiome.
我们之前的研究揭示了一种通用感受系统的存在，该系统调节细胞与其环境之间的相互作用。这个系统由原核细胞和真核细胞表面发现的基于DNA和RNA的刺果苔受体（TezRs）以及整合酶和重组酶组成。在当前的研究中，我们旨在进一步深入了解TezR在金黄色葡萄球菌基因转录中的调节作用及其缺失情况。为此，在破坏TezRs后对金黄色葡萄球菌MSSA VT209进行了转录组分析。从经核酸酶处理和未经处理的金黄色葡萄球菌MSSA VT209中提取细菌RNA样本。在破坏金黄色葡萄球菌基于DNA、RNA或DNA和RNA组合的TezRs后，分别有103、150和93个基因表达存在显著差异。分析揭示了不同TezRs缺失后基因表达的差异聚类，突出了基于DNA和RNA的TezRs缺失后的个体细胞反应。KEGG通路基因富集分析表明，TezR失活后上调最明显的通路包括与能量代谢、细胞壁代谢和分泌系统相关的通路。一些遗传通路与生物膜形成的抑制和抗生素耐药性增加有关，我们通过体外研究在表型水平上证实了这一点。这项研究的结果进一步证明了通用感受系统在细胞调节中发挥着重要作用，包括细胞对临床重要病原体环境因素的反应，并且基于核酸的TezRs是细胞外生物群落中具有功能活性的部分。
