Díaz Caridad, Pérez Del Palacio José, Valero-Guillén Pedro Luis, Mena García Patricia, Pérez Irene, Vicente Francisca, Martín Carlos, Genilloud Olga, Sánchez Pozo Antonio, Gonzalo-Asensio Jesús
Fundación MEDINA, Parque Tecnológico de Ciencias de la Salud , Avenida del Conocimiento 34 , 18016 Granada , Spain.
Departamento de Genética y Microbiología, Facultad de Medicina, Universidad de Murcia , Instituto Murciano de Investigación Biosanitaria (IMIB), Campus de Espinardo , 30100 Murcia , Spain.
ACS Infect Dis. 2019 Aug 9;5(8):1317-1326. doi: 10.1021/acsinfecdis.9b00008. Epub 2019 May 30.
MTBVAC is a live attenuated vaccine constructed by genetic deletions in the and virulence genes. The MTBVAC vaccine is currently in phase 2 clinical trials with newborns and adults in South Africa, one of the countries with the highest incidence. Although MTBVAC has been extensively characterized by genomics, transcriptomics, lipidomics, and proteomics, its metabolomic profile is yet unknown. Accordingly, in this study we aim to identify differential metabolites between and MTBVAC. To this end, an untargeted metabolomics approach based on liquid chromatography coupled to high-resolution mass spectrometry was implemented in order to explore the main metabolic differences between and MTBVAC. As an outcome, we identified a set of 34 metabolites involved in diverse bacterial biosynthetic pathways. A consistent increase in the phosphatidylinositol species was observed in the vaccine candidate relative to its parental strain. This phenotype resulted in an increased production of phosphatidylinositol mannosides, a novel PhoP-regulated phenotype in the most widespread lineages of . This study represents a step ahead in our understanding of the MTBVAC vaccine, and some of the differential metabolites identified in this work might be used as potential vaccination biomarkers.
MTBVAC是一种通过缺失和毒力基因构建的减毒活疫苗。MTBVAC疫苗目前正在南非对新生儿和成年人进行2期临床试验，南非是发病率最高的国家之一。尽管MTBVAC已通过基因组学、转录组学、脂质组学和蛋白质组学进行了广泛表征，但其代谢组学特征尚不清楚。因此，在本研究中，我们旨在鉴定和MTBVAC之间的差异代谢物。为此，实施了一种基于液相色谱与高分辨率质谱联用的非靶向代谢组学方法，以探索和MTBVAC之间的主要代谢差异。结果，我们鉴定出一组参与多种细菌生物合成途径的34种代谢物。相对于其亲本菌株，在候选疫苗中观察到磷脂酰肌醇种类持续增加。这种表型导致磷脂酰肌醇甘露糖苷产量增加，这是在最广泛的谱系中一种新的PhoP调节表型。这项研究代表了我们对MTBVAC疫苗理解的进一步深入，并且在这项工作中鉴定出的一些差异代谢物可能用作潜在的疫苗接种生物标志物。
