Wagley Sariqa, Vanaporn Muthita, Rinchai Darawan, Conejero Laura, Lertmemongkolchai Ganjana, Bancroft Gregory J, Titball Richard W
College of Life and Environmental Sciences, University of Exeter, Exeter, Devon, EX4 4QD, UK.
Department of Microbiology and Immunology, Mahidol University, Rajvithi Road, Bangkok, 10400, Thailand.
Microb Pathog. 2017 Jun;107:175-180. doi: 10.1016/j.micpath.2017.03.015. Epub 2017 Mar 18.
The NRPS/PKS cluster encodes the enzymes necessary for glidobactin synthesis it is partially conserved in various members of the Burkholderia genus including B. pseudomallei. In this study we have shown that the insertional inactivation or deletion of glbC in this cluster in B. pseudomallei could reduce the ability of the bacterium to survive or grow in murine macrophages or in human neutrophils. Exogenously added proteasome inhibitors were able to chemically complement the mutation. The insertional inactivation or deletion of glbC increased virulence in an acute model of infection in Balb/c or C57BL/6 mice but virulence in a chronic model of infection was similar to that of the wild type. Our findings contrast with the previous finding that inactivation of the glb gene cluster in B. pseudomallei strain 1026b resulted in marked attenuation, and provides evidence of differential roles for some genes in virulence of different strains of B. pseudomallei.
NRPS/PKS基因簇编码了合成格利多菌素所需的酶，它在伯克霍尔德菌属的各种成员（包括假鼻疽伯克霍尔德菌）中部分保守。在本研究中，我们表明，假鼻疽伯克霍尔德菌中该基因簇中glbC的插入失活或缺失会降低该细菌在小鼠巨噬细胞或人类中性粒细胞中存活或生长的能力。外源添加的蛋白酶体抑制剂能够化学互补该突变。glbC的插入失活或缺失在Balb/c或C57BL/6小鼠的急性感染模型中增加了毒力，但在慢性感染模型中的毒力与野生型相似。我们的发现与之前的发现形成对比，之前发现假鼻疽伯克霍尔德菌1026b菌株中glb基因簇的失活导致明显减毒，并为假鼻疽伯克霍尔德菌不同菌株中某些基因在毒力中的不同作用提供了证据。
