Silva Teane M A, Mol Juliana P S, Winter Maria G, Atluri Vidya, Xavier Mariana N, Pires Simone F, Paixão Tatiane A, Andrade Hélida M, Santos Renato L, Tsolis Renee M
Departamento de Clínica e Cirurgia Veterinária, Escola de Veterinária da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Department of Medical Microbiology and Immunology, University of California Davis, Davis, California, United States of America.
PLoS One. 2014 Dec 4;9(12):e114532. doi: 10.1371/journal.pone.0114532. eCollection 2014.
Brucella ovis is a major cause of reproductive failure in rams and it is one of the few well-described Brucella species that is not zoonotic. Previous work showed that a B. ovis mutant lacking a species-specific ABC transporter (ΔabcBA) was attenuated in mice and was unable to survive in macrophages. The aim of this study was to evaluate the role of this ABC transporter during intracellular survival of B. ovis. In HeLa cells, B. ovis WT was able to survive and replicate at later time point (48 hpi), whereas an ΔabcBA mutant was attenuated at 24 hpi. The reduced survival of the ΔabcBA mutant was associated with a decreased ability to exclude the lysosomal marker LAMP1 from its vacuolar membrane, suggesting a failure to establish a replicative niche. The ΔabcBA mutant showed a reduced abundance of the Type IV secretion system (T4SS) proteins VirB8 and VirB11 in both rich and acid media, when compared to WT B. ovis. However, mRNA levels of virB1, virB8, hutC, and vjbR were similar in both strains. These results support the notion that the ABC transporter encoded by abcEDCBA or its transported substrate acts at a post-transcriptional level to promote the optimal expression of the B. ovis T4SS within infected host cells.
绵羊布鲁氏菌是公羊繁殖失败的主要原因,它是少数几种已被充分描述的非人畜共患病布鲁氏菌之一。先前的研究表明,一种缺乏物种特异性ABC转运蛋白的绵羊布鲁氏菌突变体(ΔabcBA)在小鼠体内减毒,且无法在巨噬细胞中存活。本研究的目的是评估这种ABC转运蛋白在绵羊布鲁氏菌细胞内存活过程中的作用。在HeLa细胞中,绵羊布鲁氏菌野生型(WT)能够在较晚时间点(感染后48小时)存活并复制,而ΔabcBA突变体在感染后24小时就表现出减毒。ΔabcBA突变体存活率降低与从其液泡膜中排除溶酶体标记物LAMP1的能力下降有关,这表明无法建立复制龛。与野生型绵羊布鲁氏菌相比,ΔabcBA突变体在丰富培养基和酸性培养基中IV型分泌系统(T4SS)蛋白VirB8和VirB11的丰度均降低。然而,两种菌株中virB1、virB8、hutC和vjbR的mRNA水平相似。这些结果支持以下观点:由abcEDCBA编码的ABC转运蛋白或其转运底物在转录后水平发挥作用,以促进感染宿主细胞内绵羊布鲁氏菌T4SS的最佳表达。