Brucella abortus cyclic β-1,2-glucan mutants have reduced virulence in mice and are defective in intracellular replication in HeLa cells
Brucella abortus cyclic β-1,2-glucan mutants have reduced virulence in mice and are defective in intracellular replication in HeLa cells
复制标题
DOI：
10.1128/iai.69.7.4528-4535.2001
复制
发表时间：
2001-07-01
影响因子：
3.1
通讯作者：
Ugalde, RA
中科院分区：
文献类型：
--
作者：
Briones, G;De Iannino, NI;Ugalde, RA
空环β-1,2-葡聚糖合成酶突变体（腿突变体）是从流产布鲁氏菌强毒菌株2308和流产布鲁氏菌减毒疫苗菌株S19获得的。两种突变体都比亲本菌株对脱氧胆酸、十二烷基硫酸钠和两性试剂等表面活性剂表现出更高的敏感性，表明细胞表面发生了改变。尽管程度不同，但这两种突变体在小鼠中均表现出毒力降低，并且在 HeLa 细胞中表现出细胞内增殖缺陷。 4周后，B, abortus S19 cgs突变体从小鼠脾脏中完全清除，而2308突变体在12周后显示从脾脏中分离的布鲁氏菌数量减少了1.5个对数，这些结果表明，环β-1,2-葡聚糖在减毒B, abortus S19菌株的残余毒力中发挥着重要作用，尽管cgs突变体从小鼠脾脏中清除。与野生型亲本菌株（B，abortus 819）相比，该菌株更早地进入脾脏并产生较少的炎症反应，其针对强毒菌株B，abortus 2308的保护能力被完全保留。在注射流产布鲁氏菌 S19 或 cgs 突变体的小鼠中观察到诱导脾脏 γ 干扰素 mRNA 和抗免疫球蛋白 G2a (IgG2a) 亚型抗体的脂多糖 (LPS) 的水平相同。然而，cgs突变体诱导的IgG1亚型的抗LPS抗体滴度低于亲本819菌株观察到的滴度，因此表明cgs突变体诱导相对排他的Th1反应。
Null cyclic beta -1,2-glucan synthetase mutants legs mutants) were obtained from Brucella abortus virulent strain 2308 and from B. abortus attenuated vaccinal strain S19, Both mutants show greater sensitivity to surfactants like deoxycholic acid, sodium dodecyl sulfate, and Zwittergent than the parental strains, suggesting cell surface alterations. Although not to the same extent, both mutants display reduced virulence in mice and defective intracellular multiplication in HeLa cells. The B, abortus S19 cgs mutant was completely cleared from the spleens of mice after 4 weeks, while the 2308 mutant showed a 1.5-log reduction of the number of brucellae isolated from the spleens after 12 weeks, These results suggest that cyclic beta -1,2-glucan plays an important role in the residual virulence of the attenuated B, abortus S19 strain, Although the cgs mutant was cleared from the spleens earlier than the wild-type parental strain (B, abortus 819) and produced less inflammatory response, its ability to confer protection against the virulent strain B, abortus 2308 was fully retained. Equivalent levels of induction of spleen gamma interferon mRNA and anti-lipopolysaccharide (LPS) of immunoglobulin G2a (IgG2a) subtype antibodies were observed in mice injected with B. abortus S19 or the cgs mutant. However, the titer of anti-LPS antibodies of the IgG1 subtype induced by the cgs mutant was lower than that observed with the parental 819 strain, thus suggesting that the cgs mutant induces a relatively exclusive Th1 response.