Brinig Mary M, Register Karen B, Ackermann Mark R, Relman David A
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA.
Genome Biol. 2006;7(9):R81. doi: 10.1186/gb-2006-7-9-r81.
The respiratory pathogen Bordetella parapertussis is a valuable model in which to study the complex phenotype of host specificity because of its unique two-species host range. One subset of strains, including the sequenced representative, causes whooping cough in humans, while other strains infect only sheep. The disease process in sheep is not well understood, nor are the genetic and transcriptional differences that might provide the basis for host specificity among ovine and human strains.
We found 40 previously unknown genomic regions in an ovine strain of B. parapertussis using subtractive hybridization, including unique lipopolysaccharide genes. A microarray survey of the gene contents of 71 human and ovine strains revealed further differences, with 47 regions of difference distinguishing the host-restricted subgroups. In addition, sheep and human strains displayed distinct whole-genome transcript abundance profiles. We developed an animal model in which sheep were inoculated with a sheep strain, human strain, or mixture of the two. We found that the ovine strain persisted in the nasal cavity for 12 to 14 days, while the human strain colonized at lower levels and was no longer detected by 7 days post-inoculation. The ovine strain induced less granulocyte infiltration of the nasal mucosa.
Several factors may play a role in determining host range of B. parapertussis. Human- and ovine-associated strains have differences in content and sequence of genes encoding proteins that mediate host-pathogen contact, such as lipopolysaccharide and fimbriae, as well as variation in regulation of toxins, type III secretion genes, and other virulence-associated genes.
呼吸道病原体副百日咳博德特氏菌是研究宿主特异性复杂表型的一个有价值的模型,因为它具有独特的双物种宿主范围。其中一部分菌株,包括已测序的代表性菌株,可导致人类患百日咳,而其他菌株仅感染绵羊。绵羊的疾病过程尚未完全了解,导致绵羊和人类菌株宿主特异性差异的遗传和转录差异也不清楚。
我们利用消减杂交技术在一株副百日咳博德特氏菌绵羊菌株中发现了40个以前未知的基因组区域,包括独特的脂多糖基因。对71株人类和绵羊菌株的基因内容进行的微阵列调查揭示了更多差异,有47个差异区域区分了宿主限制亚组。此外,绵羊和人类菌株表现出不同的全基因组转录本丰度谱。我们建立了一个动物模型,给绵羊接种绵羊菌株、人类菌株或两者的混合物。我们发现绵羊菌株在鼻腔中持续存在12至14天,而人类菌株定殖水平较低,接种后7天就不再检测到。绵羊菌株诱导的鼻黏膜粒细胞浸润较少。
几个因素可能在决定副百日咳博德特氏菌的宿主范围中起作用。与人类和绵羊相关的菌株在编码介导宿主-病原体接触的蛋白质的基因内容和序列上存在差异,如脂多糖和菌毛,以及毒素、III型分泌基因和其他毒力相关基因的调控变化。