The arginine/ornithine binding protein ArgT plays an essential role in Brucella neotomae/Brucella melitensis to prevent intracellular killing and contribute to chronic persistence in the host.

IF 5.5 1区 农林科学 Q1 IMMUNOLOGY Virulence Pub Date : 2024-12-01 Epub Date: 2024-11-04 DOI:10.1080/21505594.2024.2421983
Sushree Rekha Mallik, Kiranmai Joshi, Girish K Radhakrishnan
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Abstract

Brucella species are facultative intracellular bacterial pathogens that cause the contagious zoonotic disease, brucellosis. Brucella spp. infect a wide range of animals, including livestock, wild animals, and marine mammals. Compared with other invasive bacterial pathogens, partial information is available on the virulence factors of Brucella that enable them to survive in the host. Here, we performed transposon-based random mutagenesis of B. neotomae and identified the arginine/ornithine binding protein, ArgT, as one of the crucial virulence determinants of Brucella. Deleting ArgT from B. neotomae or B. melitensis resulted in its attenuation in macrophages, which was restored upon complementation with an ArgT expression plasmid. We observed that macrophages infected with ΔArgT-B. neotomae produced elevated levels of NO due to the inability of these mutants to deplete the host intracellular arginine through their importer. Furthermore, defective survival of ΔArgT B. neotomae and B. melitensis was observed in the infected mice, which correlated with enhanced NO production in the mice. Our studies revealed that ArgT plays a vital role in preventing intracellular killing and contributes to the chronic persistence of B. neotomae/B. melitensis in the host. This study highlights the essential role of arginine in clearing intracellular infections and the subversion of this host defense mechanism by intracellular pathogens for their chronic persistence.

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精氨酸/鸟氨酸结合蛋白 ArgT 在新布鲁氏菌/梅毒布鲁氏菌中发挥着重要作用,可防止细胞内杀灭,并有助于在宿主体内长期存活。
布鲁氏菌属是一种细胞内细菌病原体,可引起传染性人畜共患病--布鲁氏菌病。布鲁氏菌属可感染多种动物,包括家畜、野生动物和海洋哺乳动物。与其他入侵性细菌病原体相比,目前关于布鲁氏菌在宿主体内存活的毒力因子的信息还很不全面。在这里,我们对布鲁氏菌进行了基于转座子的随机诱变,发现精氨酸/鸟氨酸结合蛋白 ArgT 是布鲁氏菌的关键毒力决定因子之一。从新布鲁氏菌或梅毒布鲁氏菌中删除 ArgT 会导致其在巨噬细胞中的作用减弱,而在与 ArgT 表达质粒互补后又会恢复。我们观察到,感染了 ΔArgT-B. neotomae 的巨噬细胞会产生较高水平的 NO,这是因为这些突变体无法通过它们的导入器消耗宿主细胞内的精氨酸。此外,在受感染的小鼠体内观察到 ΔArgT B. neotomae 和 B. melitensis 的存活缺陷,这与小鼠体内 NO 生成的增加有关。我们的研究揭示了 ArgT 在阻止细胞内杀灭中的重要作用,并有助于新黑头瘤鼻疽杆菌/黑头瘤鼻疽杆菌在宿主体内的慢性存活。这项研究强调了精氨酸在清除细胞内感染中的重要作用,以及细胞内病原体对这种宿主防御机制的颠覆,使其长期存在。
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来源期刊
Virulence
Virulence IMMUNOLOGY-MICROBIOLOGY
CiteScore
9.20
自引率
1.90%
发文量
123
审稿时长
6-12 weeks
期刊介绍: Virulence is a fully open access peer-reviewed journal. All articles will (if accepted) be available for anyone to read anywhere, at any time immediately on publication. Virulence is the first international peer-reviewed journal of its kind to focus exclusively on microbial pathogenicity, the infection process and host-pathogen interactions. To address the new infectious challenges, emerging infectious agents and antimicrobial resistance, there is a clear need for interdisciplinary research.
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