Abstract:
Brucella spp. are Gram-negative bacteria that naturally infect a variety of domesticated and wild animals, often resulting in abortions and sterility. Humans exposed to these animals or animal products can also develop debilitating, flu-like disease. The brucellae are intracellular pathogens that reside predominantly within immune cells, typically macrophages, where they replicate in a specialized compartment. This capacity of Brucella to survive and replicate within macrophages is essential to their ability to cause disease. In recent years, several groups have identified and characterized small regulatory RNAs (sRNAs) as critical factors in the control of Brucella physiology within macrophages and overall disease virulence. sRNAs are generally < 300 nucleotides in length, and these independent sRNA transcripts are encoded either next to (i.e., cis-encoded) or at a distant location to (i.e., trans-encoded) the genes that they regulate. Trans-encoded sRNAs interact with the mRNA transcripts through short stretches of imperfect base pairing that often require the RNA chaperone Hfq to facilitate sRNA-mRNA interaction. In many instances, these sRNA-mRNA interactions inhibit gene expression, usually by occluding the ribosome-binding site (RBS) and/or by decreasing the stability of the mRNA, leading to degradation of the transcript. A number of sRNAs have been predicted and authenticated in Brucella strains, and a variety of approaches, techniques, and means of validation have been employed in these efforts. Nonetheless, some important issues and considerations regarding the study of sRNA regulation in Brucella need to be addressed. For example, the lack of uniform sRNA nomenclature in Brucella has led to difficulty in comparisons of sRNAs across the different Brucella species, and there exist multiple names in the literature for what are functionally the same sRNA. Moreover, even though bona fide sRNAs have been discovered in Brucella, scant functional information is known about the regulatory activities of these sRNAs, or the extent to which these sRNAs are required for the intracellular life and/or host colonization by the brucellae. Therefore, this review summarizes the historical context of Hfq and sRNAs in Brucella; our current understanding of Brucella sRNAs; and some future perspectives and considerations for the field of sRNA biology in the brucellae.
摘要:
布鲁氏菌属。是革兰氏阴性细菌,自然感染各种驯养和野生动物,经常导致流产和不育。暴露于这些动物或动物产品的人类也会变得衰弱,流感样疾病。布鲁氏菌是细胞内病原体,主要存在于免疫细胞内,通常是巨噬细胞,他们在一个专门的隔间里复制。布鲁氏菌在巨噬细胞内存活和复制的这种能力对于它们引起疾病的能力至关重要。近年来,几个小组已经鉴定并表征了小调节RNA(sRNA)作为控制巨噬细胞内布鲁氏菌生理和整体疾病毒力的关键因素。sRNA的长度通常<300个核苷酸,并且这些独立的sRNA转录物被编码在(即,顺式编码)或在远处的位置(即,反式编码)它们调节的基因。反式编码的sRNA通过不完全碱基配对的短延伸与mRNA转录物相互作用,这通常需要RNA伴侣Hfq来促进sRNA-mRNA相互作用。在许多情况下,这些sRNA-mRNA相互作用抑制基因表达,通常通过封闭核糖体结合位点(RBS)和/或通过降低mRNA的稳定性,导致抄本退化。已经在布鲁氏菌菌株中预测和鉴定了许多sRNAs,和各种方法,技术,并在这些努力中采用了验证手段。尽管如此,关于布鲁氏菌sRNA调控研究的一些重要问题和注意事项需要解决。例如,布鲁氏菌中缺乏统一的sRNA命名法导致难以比较不同布鲁氏菌种的sRNA,并且在文献中存在多个功能相同的sRNA的名称。此外,尽管在布鲁氏菌中发现了真正的sRNAs,关于这些sRNAs的调节活动的功能信息很少,或这些sRNA是布鲁氏菌的细胞内生命和/或宿主定殖所需的程度。因此,这篇综述总结了布鲁氏菌中Hfq和sRNA的历史背景;我们目前对布鲁氏菌sRNA的理解;以及布鲁氏菌sRNA生物学领域的一些未来观点和考虑。