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23 January 2009PloS Pathogens, edited by Infection Research
The fruit fly as an in vivo model to study polymicrobial infections
Many human infectious diseases are characterised by the presence of more than one bacterial species. Scientists developed a Drosophila melanogaster model to study the complex interactions in vivo, they report in the open-access journal PloS Pathogens.
The hereditary disease cystic fibrosis affects the exocrine glands of the lungs and other organs. Due to the thick mucus in airways patients develop a chronic bacterial colonisation of the usually sterile airways. Pseudomonas aeruginosa is considered the most relevant pathogen of this polymicobial community. Much is known about this bacterium but little about the other bacteria and their interactions.
Christopher Sibley and colleagues from the University of Calgary, Canada, used a Drosophila model to investigate these interactions. Using an insect to study complex human infections seems feasible because „regardless of the diverse host range, P. aeruginosa utilizes common virulence mechanisms and genes necessary for mammalian pathogenesis are also essential for pathogenicity in the fruit fly“, the researchers write.
They collected sputum samples from patients chronically infected with P. aeruginosa and cultivated non-P. aeruginosa strains. 40 of these isolates were fed to Drosophila alone and in combination with P. aeruginosa. Monitoring the fly survival rates the strains could be assigned to three different categories: Virulent strains able to kill flies, avirulent strains unable to kill flies, and synergistic organisms not pathogenic to flies alone but in combination with P. aeruginosa dramatically reducing fly survival.
To investigate if this synergistic effect may result from altered P. aeruginosa gene expression they used modified P. aeruginosa virulence factor reporter strains to monitor gene expression of 24 different virulence factors. Flies were infected with one of these strains alone or in combination with a synergistic Streptococcus species, showing that combined infection changed the activation profile of virulence factors. In another experiment the researchers showed that mixed infections also altered the innate immune response of the fly. „The Drosophila model of polymicrobial infections not only allows relevant microbe-microbe interaction to be easily discerned based on fly survival but also provides a framework to further discriminate these interactions by assaying both bacterial and host gene expression in vivo“, the authors conclude.
Read the full paper in PloS Pathogens
Sibley CD, Duan K, Fischer C, Parkins MD, Storey DG, et al. (2008) Discerning the Complexity of Community Interactions Using a Drosophila Model of Polymicrobial Infections. PLoS Pathog 4(10): e1000184. doi:10.1371/journal.ppat.1000184
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