研究 HpuB 中某些表面暴露环对淋病奈瑟菌结合和利用血红蛋白的重要性。

IF 2.9 3区 医学 Q3 IMMUNOLOGY Infection and Immunity Pub Date : 2024-07-11 Epub Date: 2024-06-12 DOI:10.1128/iai.00211-24
Olivia A Awate, Dixon Ng, Julie L Stoudenmire, Trevor F Moraes, Cynthia N Cornelissen
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引用次数: 0

摘要

淋病奈瑟菌是性传播感染淋病的病原体。由于感染后不会产生保护性免疫,而且随着抗菌素耐药性的增加,可供选择的治疗方法也越来越少,因此该病原体是一项全球性的健康挑战。由于没有有效的疫苗,研究人员正在探索疫苗开发和创新疗法的新目标。淋球菌产生的外膜TonB依赖性转运体(TdTs)被认为是有希望的疫苗抗原,因为它们具有高度保守性,在克服营养免疫方面发挥着关键作用。其中一种 TdTs 是由 HpuA 和 HpuB 组成的血红蛋白转运系统的一部分。该系统允许淋球菌从血红蛋白(hHb)中获取铁。在目前的研究中,为了更好地了解 HpuB 的结构-功能关系,对 hpuB 基因进行了突变。这项研究首次证明淋球菌可以结合并利用人类以外的动物产生的血红蛋白。这项研究还确定,当 HpuA 缺失时,针对 HpuB 细胞外环 7 的突变会导致 hHb 结合和利用缺陷。然而,当脂蛋白 HpuA 存在时,这些环路 7 突变体恢复了与 hHb 结合的能力,尽管生长表型仍然明显受损。有趣的是,环 7 包含假定的血红素结合基团和一个假定的 α 螺旋区域,这两个基团可能对 hHb 的利用都很重要。综上所述,这些结果凸显了环路 7 在 HpuB 结合 hHb 以及提取和内化铁的功能中的重要性。
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Investigating the importance of selected surface-exposed loops in HpuB for hemoglobin binding and utilization by Neisseria gonorrhoeae.

Neisseria gonorrhoeae is the etiological agent of the sexually transmitted infection gonorrhea. The pathogen is a global health challenge since no protective immunity results from infection, and far fewer treatment options are available with increasing antimicrobial resistance. With no efficacious vaccines, researchers are exploring new targets for vaccine development and innovative therapeutics. The outer membrane TonB-dependent transporters (TdTs) produced by N. gonorrhoeae are considered promising vaccine antigens as they are highly conserved and play crucial roles in overcoming nutritional immunity. One of these TdTs is part of the hemoglobin transport system comprised of HpuA and HpuB. This system allows N. gonorrhoeae to acquire iron from hemoglobin (hHb). In the current study, mutations in the hpuB gene were generated to better understand the structure-function relationships in HpuB. This study is one of the first to demonstrate that N. gonorrhoeae can bind to and utilize hemoglobin produced by animals other than humans. This study also determined that when HpuA is absent, mutations targeting extracellular loop 7 of HpuB led to defective hHb binding and utilization. However, when the lipoprotein HpuA is present, these loop 7 mutants recovered their ability to bind hHb, although the growth phenotype remained significantly impaired. Interestingly, loop 7 contains putative heme-binding motifs and a hypothetical α-helical region, both of which may be important for the use of hHb. Taken together, these results highlight the importance of loop 7 in the functionality of HpuB in binding hHb and extracting and internalizing iron.

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来源期刊
Infection and Immunity
Infection and Immunity 医学-传染病学
CiteScore
6.00
自引率
6.50%
发文量
268
审稿时长
3 months
期刊介绍: Infection and Immunity (IAI) provides new insights into the interactions between bacterial, fungal and parasitic pathogens and their hosts. Specific areas of interest include mechanisms of molecular pathogenesis, virulence factors, cellular microbiology, experimental models of infection, host resistance or susceptibility, and the generation of innate and adaptive immune responses. IAI also welcomes studies of the microbiome relating to host-pathogen interactions.
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