PDF(Pubmed)
Abstract：
Tuberculosis (TB) continues to be a major global health burden and kills over a million people annually. New immunization strategies are required for the development of an efficacious TB vaccine that can potentially induce sterilizing immunity. In this study, we first confirmed that a live vaccine strain of Mycobacterium smegmatis, previously designated as IKEPLUS, conferred a higher survival benefit than the Bacillus Calmette-Guerin (BCG) in a murine model of intravenous Mycobacterium tuberculosis (Mtb) infection. We have shown that there was a significant increase in the expression of the Rv0282 gene, which is encoded in the esx-3 locus, which played an important role in iron uptake when IKEPLUS was grown in both low zinc and iron-containing Sauton medium. We then confirmed using in vitro assays of biofilm formation that zinc plays a vital role in the growth and formation of M. smegmatis biofilms. IKEPLUS grown in low zinc media led to the better protection of mice after intravenous challenge with a very high dosage of Mtb. We also showed that various variants of IKEPLUS induced apoptotic cell-death of infected macrophages at a higher rate than wild-type M. smegmatis. We next attempted to determine if zinc containing ribosomal proteins such as rpmb2 could contribute to protective efficacy against Mtb infection. Since BCG has an established role in anti-mycobacterial efficacy, we boosted BCG vaccinated mice with rmpb2, but this did not lead to an increment in the protection mediated by BCG.
摘要：
结核病（TB）仍然是全球主要的健康负担，每年造成100多万人死亡。开发有效的TB疫苗需要新的免疫策略，该疫苗可以潜在地诱导灭菌免疫。在这项研究中,我们首先证实了耻垢分枝杆菌的活疫苗株，以前指定为IKEPLUS，在静脉结核分枝杆菌（Mtb）感染的小鼠模型中，与卡介苗（BCG）相比，具有更高的生存益处。我们已经证明Rv0282基因的表达显著增加，它被编码在esx-3基因座中，当IKEPLUS在低锌和含铁的Sauton培养基中生长时，这在铁的吸收中起着重要作用。然后，我们使用生物膜形成的体外测定证实，锌在耻垢分枝杆菌生物膜的生长和形成中起着至关重要的作用。在低锌培养基中生长的IKEPLUS导致在用非常高剂量的Mtb静脉内攻击后对小鼠的更好保护。我们还表明，IKEPLUS的各种变体以比野生型耻垢分枝杆菌更高的速率诱导受感染巨噬细胞的凋亡细胞死亡。我们接下来试图确定含锌的核糖体蛋白如rpmb2是否可以有助于对抗Mtb感染的保护功效。由于BCG在抗分枝杆菌功效中具有既定作用，我们用rmpb2增强了接种BCG的小鼠,但这并未导致BCG介导的保护作用增加.
