Independent loss of immunogenic proteins in Mycobacterium ulcerans suggests immune evasion

Huber, Charlotte A., Ruf, Marie-Thérèse, Pluschke, Gerd and Käser, Michael (2008) Independent loss of immunogenic proteins in Mycobacterium ulcerans suggests immune evasion. Clinical and Vaccine Immunology, 15 4: 598-606. doi:10.1128/CVI.00472-07


Author Huber, Charlotte A.
Ruf, Marie-Thérèse
Pluschke, Gerd
Käser, Michael
Title Independent loss of immunogenic proteins in Mycobacterium ulcerans suggests immune evasion
Journal name Clinical and Vaccine Immunology   Check publisher's open access policy
ISSN 1556-6811
1556-679X
Publication date 2008-04
Sub-type Article (original research)
DOI 10.1128/CVI.00472-07
Volume 15
Issue 4
Start page 598
End page 606
Total pages 9
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Formatted abstract
The highly immunogenic mycobacterial proteins ESAT-6, CFP-10, and HspX represent potential target antigens for the development of subunit vaccines and immunodiagnostic tests. Recently, the complete genome sequence revealed the absence of these coding sequences in Mycobacterium ulcerans, the causative agent of the emerging human disease Buruli ulcer. Genome reduction and the acquisition of a cytopathic and immunosuppressive macrolide toxin plasmid are regarded as crucial for the emergence of this pathogen from its environmental progenitor, Mycobacterium marinum. Earlier, we have shown the evolution of M. ulcerans into two distinct lineages. Here, we show that while the genome of M. marinum M contains two copies of the esxB-esxA gene cluster at different loci (designated MURD4 and MURD152), both copies are deleted from the genome of M. ulcerans strains belonging to the classical lineage. Members of the ancestral lineage instead retained some but disrupted most functional MURD4 or MURD152 copies, either by newly identified genomic insertion-deletion events or by conversions of functional genes to pseudogenes via point mutations. Thus, the esxA (ESAT-6), esxB (CFP-10), and hspX genes are located in hot-spot regions for genomic variation where functional disruption seems to be favored by selection pressure. Our detailed genomic analyses have identified a variety of independent genomic changes that have led to the loss of expression of functional ESAT-6, CFP-10, and HspX proteins. Loss of these immunodominant proteins helps the bacteria bypass the host's immunological response and may represent part of an ongoing adaptation of M. ulcerans to survival in host environments that are screened by immunological defense mechanisms
Keyword Variable Number
Phagosome Maturation
Functional-Analysis
Sequence Reveals
Secretion System
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Centre for Clinical Research Publications
 
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