Differences in Inflammation Patterns Induced by African and Asian Burkholderia pseudomallei Isolates in Mice
Tassili A F Weehuizen1,2, Emma Birnie3,2,1, Bart Ferwerda4,1,2
1Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, Amsterdam, The Netherlands.
Abstract:
AbstractBurkholderia pseudomallei is the causative agent of melioidosis, an emerging tropical disease of high mortality. Sub-Saharan Africa represents potential melioidosis "hotspots"; however, to date, only a few cases have been reported. Here in, we compared the inflammatory patterns induced by a B. pseudomallei strain recently isolated from a fatal Gabonese case with the Thai reference strain B. pseudomallei-1026b and Burkholderia thailandensis-E264. Ex vivo, no differences were observed in terms of cellular responsiveness between strains. However, when compared with the B. pseudomallei-1026b strain, the Gabonese isolate was significantly less virulent in terms of bacterial dissemination, inflammatory response, and organ damage in mice. Genomic comparison between strains showed differences in regions containing a fimbriae/adhesion virulence protein. In addition to a lack of microbiology facilities, differences in virulence of Burkholderia strains might contribute to the diverse global clinical occurrence of melioidosis.
Insights
This study compared Burkholderia pseudomallei strains, finding a Gabonese isolate less virulent than a Thai strain in mice. Differences in virulence may explain varied melioidosis occurrence globally.
Area of Science:
- Microbiology
- Infectious Diseases
- Genomics
Background:
- Melioidosis, caused by Burkholderia pseudomallei, is a high-mortality tropical disease.
- Sub-Saharan Africa is a potential hotspot for melioidosis, yet few cases are reported.
- Strain virulence may influence global disease distribution.
Purpose of the Study:
- To compare the inflammatory responses and virulence of a Gabonese B. pseudomallei isolate against reference strains.
- To investigate genomic differences potentially linked to virulence variations.
Main Methods:
- Ex vivo analysis of cellular responsiveness to different Burkholderia strains.
- In vivo virulence assessment in a mouse model (bacterial dissemination, inflammation, organ damage).
- Genomic comparison of B. pseudomallei strains.
Main Results:
- No significant ex vivo differences in cellular responsiveness were observed between strains.
- The Gabonese B. pseudomallei isolate exhibited significantly lower virulence in mice compared to the Thai reference strain.
- Genomic analysis revealed differences in virulence factor genes, including fimbriae/adhesion proteins.
Conclusions:
- Virulence variations among Burkholderia strains could contribute to the differing clinical incidence of melioidosis worldwide.
- Limited microbiology infrastructure may also impact reported melioidosis cases in regions like Sub-Saharan Africa.
