Posadas Diana M, Martín Fernando A, Sabio y García Julia V, Spera Juan M, Delpino M Victoria, Baldi Pablo, Campos Eleonora, Cravero Silvio L, Zorreguieta Angeles
Fundación Instituto Leloir, Patricias Argentinas 435, C1405BWE Buenos Aires, Argentina.
Infect Immun. 2007 Jan;75(1):379-89. doi: 10.1128/IAI.01349-06. Epub 2006 Nov 6.
Brucella spp., like other pathogens, must cope with the environment of diverse host niches during the infection process. In doing this, pathogens evolved different type of transport systems to help them survive and disseminate within the host. Members of the TolC family have been shown to be involved in the export of chemically diverse molecules ranging from large protein toxins to small toxic compounds. The role of proteins from the TolC family in Brucella and other alpha-2-proteobacteria has been explored little. The gene encoding the unique member of the TolC family from Brucella suis (BepC) was cloned and expressed in an Escherichia coli mutant disrupted in the gene encoding TolC, which has the peculiarity of being involved in diverse transport functions. BepC fully complemented the resistance to drugs such as chloramphenicol and acriflavine but was incapable of restoring hemolysin secretion in the tolC mutant of E. coli. An insertional mutation in the bepC gene strongly affected the resistance phenotype of B. suis to bile salts and toxic chemicals such as ethidium bromide and rhodamine and significantly decreased the resistance to antibiotics such as erythromycin, ampicillin, tetracycline, and norfloxacin. Moreover, the B. suis bepC mutant was attenuated in the mouse model of infection. Taken together, these results suggest that BepC-dependent efflux processes of toxic compounds contribute to B. suis survival inside the host.
布鲁氏菌属与其他病原体一样,在感染过程中必须应对宿主不同生态位的环境。在此过程中,病原体进化出不同类型的转运系统,以帮助它们在宿主体内生存和传播。已证明TolC家族成员参与从大的蛋白质毒素到小的有毒化合物等化学性质各异的分子的输出。TolC家族蛋白在布鲁氏菌和其他α-2-变形杆菌中的作用鲜有研究。克隆了来自猪布鲁氏菌的TolC家族独特成员(BepC)的基因,并在编码TolC的基因被破坏的大肠杆菌突变体中表达,该突变体具有参与多种转运功能的特性。BepC完全恢复了对氯霉素和吖啶黄等药物的抗性,但无法恢复大肠杆菌tolC突变体中的溶血素分泌。bepC基因的插入突变强烈影响猪布鲁氏菌对胆盐和溴化乙锭、罗丹明等有毒化学物质的抗性表型,并显著降低对红霉素、氨苄青霉素、四环素和诺氟沙星等抗生素的抗性。此外,猪布鲁氏菌bepC突变体在感染小鼠模型中减毒。综上所述,这些结果表明,依赖BepC的有毒化合物外排过程有助于猪布鲁氏菌在宿主体内的存活。