State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing, China.
Lab for Bacteriology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing, China.
Front Cell Infect Microbiol. 2022 May 4;12:874773. doi: 10.3389/fcimb.2022.874773. eCollection 2022.
is the etiological agent of plague, a deadly infectious disease that has caused millions of deaths throughout history. Obtaining iron from the host is very important for bacterial pathogenicity possesses many iron uptake systems. Yersiniabactin (Ybt) plays a major role in iron uptake and , and in virulence toward mice as well. FyuA, a β-barrel TonB-dependent outer membrane protein, serves as the receptor for Ybt. In this study, we examined the role of the gene in virulence using different challenging ways and explored the underlying mechanisms. The BALB/c mouse infection assay showed that the virulence of the mutant strains (Δ and Δ) was lower when compared with that of the wild-type (WT) strain 201. Furthermore, the attenuation of virulence of the mutant strains subcutaneous and intraperitoneal challenges was far greater than that intravenous injection. Iron supplementation restored lethality during subcutaneous challenge with the two mutants. Thus, we speculated that the attenuated virulence of the mutant strains toward the mice may be caused by dysfunctional iron uptake. Moreover, Δ and Δ strains exhibited lower survival rates in murine RAW264.7 macrophages, which might be another reason for the attenuation. We further explored the transcriptomic differences between the WT and mutant strains at different temperatures and found that the expressions of genes related to Ybt synthesis and its regulation were significantly downregulated in the mutant strains. This finding indicates that might exert a regulatory effect on Ybt. Additionally, the expressions of the components of the type III secretion system were unexpectedly upregulated in the mutants, which is inconsistent with the conventional view that the upregulation of the virulence genes enhances the virulence of the pathogens.
是鼠疫的病原体，这种致命的传染病在历史上已经导致了数百万人死亡。从宿主中获取铁对于细菌的致病性非常重要，因为它拥有许多铁摄取系统。耶尔森菌素（Ybt）在铁摄取中起着重要作用 和 ，并且对小鼠的毒力也有影响。FyuA 是一种β桶 TonB 依赖性外膜蛋白，作为 Ybt 的受体。在这项研究中，我们使用不同的挑战方法研究了 基因在毒力中的作用，并探讨了潜在的机制。BALB/c 小鼠感染实验表明，与野生型（WT）菌株 201 相比，突变菌株（Δ 和 Δ）的毒力较低。此外，突变菌株在皮下和腹腔挑战中的毒力衰减要远远大于静脉注射。铁补充恢复了这两种突变体在皮下挑战中的致死性。因此，我们推测突变菌株对小鼠的毒力减弱可能是由于铁摄取功能失调所致。此外，Δ 和 Δ 菌株在小鼠 RAW264.7 巨噬细胞中的存活率较低，这可能也是毒力减弱的另一个原因。我们进一步探索了 WT 和突变菌株在不同温度下的转录组差异，发现突变菌株中与 Ybt 合成及其调控相关的基因表达明显下调。这一发现表明 可能对 Ybt 发挥调节作用。此外，突变体中 III 型分泌系统组件的表达出乎意料地上调，这与传统观点相悖，即毒力基因的上调增强了病原体的毒力。
