|Brinig, Mary - UNIV. OF STANFORD, CA|
|Ackermann, Mark - IOWA STATE UNIVERSITY|
|Relman, David - VA PALO ALTO HEALTH CARE|
Submitted to: Genome Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 1, 2006
Publication Date: September 6, 2006
Citation: Brinig, M.M., Register, K.B., Ackermann, M.R., Relman, D.A. 2006. Genomic features of Bordetella parapertussis clades with distinct host species specificity. Genome Biology. 7(9):81. Interpretive Summary: Bordetella parapertussis is a respiratory pathogen that only infects humans and sheep. Some strains cause whooping cough in humans while a distinct, second group is only associated with pneumonia in sheep. The genetic differences underlying these alternate host specificities are not known. In this study, several different methods (including subtractive hybridization, microarray-based comparative genomic hybridization, and transcript abundance profiling) were used to compare the entire genome of a human strain with a sheep strain. Forty previously unknown DNA sequences were identified only in the sheep strain. Additional comparisons between 28 human strains and 43 sheep strains revealed further differences, including variation in the sequence, number, and levels of expression of genes involved in attachment and other virulence-associated traits. Inoculation of sheep with either the natural ovine pathogen or a human strain revealed that the ovine strain elicited a less intense immune response and colonized the nasal turbinate more efficiently and for a longer period of time. These data indicate host specificity of B. parapertussis is associated with adaptation of structures involved in host-pathogen contact as well as alterations in the regulation of toxins and other virulence-associated genes. This information is useful for understanding the host specificity of Bordetella infection in other animals, including swine and poultry.
Technical Abstract: Bordetella parapertussis is a respiratory pathogen with a unique host range restricted to humans and sheep. B. parapertussis causes whooping cough in humans, and a strain isolated from a patient has been sequenced, but the disease process in sheep is not well-understood, nor are the genetic and transcriptional differences between the ovine and human strains. We found 40 previously-unknown sequences in an ovine strain of B. parapertussis using subtractive hybridization, including several unique LPS genes. A microarray survey of the genome contents of a large collection of human and ovine strains revealed further differences between the two groups, including variation in the sequence and number of genes encoding a fimbrial subunit, which may act as an adhesin and an antigen; as well as regions of difference that distinguished two subgroups of ovine strains. In addition to gene content divergence, whole-genome transcriptional profiles of the sheep and human strains were significantly different, indicating that regulatory mechanisms may play a major role in the host restriction of these strains. To study the host-pathogen dynamics in a natural infection setting, we inoculated adult sheep intranasally with a sheep strain, a human strain, or both, and monitored nasal colonization and respiratory pathology. We found that the ovine strain persisted in the nasal cavity for 12-14 days, while the human strain colonized at lower levels and was no longer detected by seven days post-inoculation. Histological examination of the respiratory organs showed that the ovine strain induced a lower level of granulocyte infiltration into the nasal mucosa. These studies provide insight into mechanisms of host restriction based on large-scale transcriptional changes, which may allow an adapted pathogen to persist in a host without evoking an immune response that would lead to clearance.