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Genetic control of weight loss during pneumonic Burkholderia pseudomallei infection
Felicia D Emery1, Jyothi Parvathareddy, Ashutosh K Pandey
1Department of Microbiology, Immunology & Biochemistry, The University of Tennessee Health Science Center, Memphis, TN, USA.
Abstract:
Burkholderia pseudomallei (Bp) is the causal agent of a high-morbidity/mortality disease syndrome known as melioidosis. This syndrome can range from acute fulminate disease to chronic, local, and disseminated infections that are often difficult to treat because Bp exhibits resistance to many antibiotics. Bp is a prime candidate for use in biologic warfare/terrorism and is classified as a Tier-1 select agent by HHS and APHIS. It is known that inbred mouse strains display a range of susceptibility to Bp and that the murine infection model is ideal for studying acute melioidosis. Here, we exploit a powerful mouse genetics resource that consists of a large family of BXD-type recombinant inbred strains, to perform genome-wide linkage analysis of the weight loss phenotype following pneumonic infection with Bp. We infected parental mice and 32 BXD strains with 50-100 CFU of Bp (strain 1026b) and monitored weight retention each day over an eleven-day time course. Using the computational tools in GeneNetwork, we performed genome-wide linkage analysis to identify an interval on chromosome 12 that appears to control the weight retention trait. We then analyzed and ranked positional candidate genes in this interval, several of which have intriguing connections with innate immunity, calcium homeostasis, lipid transport, host cell growth and development, and autophagy.
Insights
Researchers identified a specific chromosome region controlling weight loss in mice infected with Burkholderia pseudomallei, the cause of melioidosis. This finding aids understanding of host susceptibility to this dangerous pathogen.
Area of Science:
- Genetics
- Immunology
- Microbiology
Background:
- Melioidosis, caused by Burkholderia pseudomallei (Bp), is a serious infection with high mortality.
- Bp's antibiotic resistance complicates treatment, and its potential as a bioweapon classifies it as a Tier-1 select agent.
- Mouse models are crucial for studying melioidosis, with varying susceptibility observed across inbred strains.
Purpose of the Study:
- To identify genetic factors influencing weight loss in mice following pneumonic Burkholderia pseudomallei infection.
- To leverage the BXD recombinant inbred mouse strain resource for genome-wide linkage analysis.
Main Methods:
- Infection of parental and 32 BXD strains of mice with Burkholderia pseudomallei (strain 1026b).
- Daily monitoring of weight retention over an eleven-day period.
- Genome-wide linkage analysis using GeneNetwork computational tools to identify quantitative trait loci (QTLs).
Main Results:
- Identification of a significant quantitative trait locus (QTL) on chromosome 12 associated with weight retention.
- Analysis and ranking of positional candidate genes within the identified QTL.
- Several candidate genes showed potential links to innate immunity, calcium homeostasis, lipid transport, cell development, and autophagy.
Conclusions:
- A specific chromosomal region on mouse chromosome 12 significantly influences the host's response to Burkholderia pseudomallei infection, as measured by weight loss.
- Positional candidate genes within this region offer potential targets for understanding host genetic control of melioidosis susceptibility.
- Further research into these candidate genes could reveal mechanisms of innate immunity and host-pathogen interactions relevant to melioidosis.
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