Brucella melitensis Rev.1 is the live attenuated Elberg-originated vaccine strain of the facultative intracellular Brucella species, and is widely used to control brucellosis in small ruminants. However, Rev.1 may cause abortions in small ruminants that have been vaccinated during the last trimester of gestation, it is pathogenic to humans, and it induces antibodies directed at the O-polysaccharide (O-PS) of the smooth lipopolysaccharide, thus making it difficult to distinguish between vaccinated and infected animals. Rough Brucella strains, which lack O-PS and are considered less pathogenic, have been introduced to address these drawbacks; however, as Rev.1 confers a much better immunity than the rough mutants, it is still considered the reference vaccine for the prophylaxis of brucellosis in small ruminants. Therefore, developing an improved vaccine strain, which lacks the Rev.1 drawbacks, is a highly evaluated task, which requires a better understanding of the molecular mechanisms underlying the virulence attenuation of Rev.1 smooth strains and of natural Rev.1 rough strains, which are currently only partly understood. As the acidification of the Brucella-containing vacuole during the initial stages of infection is crucial for their survival, identifying the genes that contribute to their survival in an acidic environment versus a normal environment will greatly assist our understanding of the molecular pathogenic mechanisms and the attenuated virulence of the Rev.1 strain. Here, we compared the transcriptomes of the smooth and natural rough Rev.1 strains, each grown under either normal or acidic conditions. We found 12 key genes that are significantly downregulated in the Rev.1 rough strains under normal pH, as compared with Rev.1 smooth strains, and six highly important genes that are significantly upregulated in the smooth strains under acidic conditions, as compared with Rev.1 rough strains. All 18 differentially expressed genes are associated with bacterial virulence and survival and may explain the attenuated virulence of the rough Rev.1 strains versus smooth Rev.1 strains, thus providing new insights into the virulence attenuation mechanisms of Brucella. These highly important candidate genes may facilitate the design of new and improved brucellosis vaccines.

布鲁氏菌布鲁氏菌Rev.1是兼性细胞内布鲁氏菌属物种的减毒活的Elberg起源的疫苗株，已广泛用于控制小型反刍动物中的布鲁氏菌病。但是，Rev.1可能会导致在妊娠的最后三个月中接种了小反刍动物的流产，对人类具有致病性，并且会诱导针对光滑脂多糖的O-多糖（O-PS）的抗体，因此很难区分接种疫苗的动物和感染的动物。粗布鲁切拉引入了缺乏O-PS并被认为具有较低致病性的菌株以解决这些缺点；但是，由于Rev.1具有比粗糙突变体更好的免疫力，因此仍被认为是预防小反刍动物布鲁氏菌病的参考疫苗。因此，开发一种没有Rev.1缺陷的改良疫苗株是一项高度评​​价的任务，需要更好地了解Rev.1平滑菌株和天然Rev.1粗菌株毒力衰减的分子机制，目前仅部分了解。作为布鲁氏菌的酸化感染初期含有大量液泡对于它们的生存至关重要，鉴定出在酸性环境与正常环境下对它们的生存有贡献的基因将极大地帮助我们了解Rev.1的分子致病机理和减毒力。拉紧。在这里，我们比较了光滑和天然的Rev.1粗菌株的转录组，每一种菌株都在正常或酸性条件下生长。我们发现，在正常pH下，Rev.1粗菌株中的12个关键基因与Rev.1平滑菌株相比显着下调；在酸性条件下，与Rev.1相比，平滑菌株中的6个重要基因显着上调。 .1粗大应变。布鲁切拉（Brucella）。这些高度重要的候选基因可能有助于设计新的和改良的布鲁氏菌病疫苗。