Flies infected via feeding with a highly virulent strain of Pseudomonas aeruginosa typically die within 20 days. Infection results in mild intestinal tissue hyperplasia, manifested by a significant increase in the width of the posterior midgut compared to that of uninfected flies and an increase in the number of intestinal stem cells; both phenotypes are reversible upon bacteria clearance.
Infection with P. aeruginosa has been combined with several Drosophila cancer models to assess the impact of bacterial infection upon normal cells of the fly gut vs cells that have been potentiated by expression of a cancer-implicated gene variant. The most extensively characterized is in combination with the activated Ras85DV12 allele, expressed specifically in the gut; a dominant-negative form of Notch (N) and RNAi knockdown of the tumor suppressor gene discs large (dlg1) have also been assessed. Higher levels of intestinal hyperplasia are observed; affected intestines develop excess layers of cells with altered apicobasal polarity reminiscent of dysplasia.
When expressed in the adult hindgut (without bacterial infection), Ras85DV12 results in delamination of hindgut cells and some dissemination of cells away from the hindgut; this phenotype is exacerbated by sustained infection with P. aeruginosa. The enhanced phenotype is reversed upon bacteria clearance.
The role of JNK signaling in these responses has been assessed.
[updated Nov. 2019 by FlyBase; FBrf0222196]
In human, Pseudomonas aeruginosa has become an important cause of gram-negative infection, especially in patients with compromised host defense mechanisms. It is the most common pathogen isolated from patients who have been hospitalized longer than 1 week. Pseudomonas infections can be life-threatening. (https://emedicine.medscape.com/article/226748-overview)
High-scoring ortholog of human genes KRAS, HRAS, and NRAS (many to many; multiple paralogs and orthologs in both species). Dmel\Ras85D shares 78-86% identity and 86-92% similarity with KRAS, HRAS, and NRAS; for these three human genes, Ras85D is the highest-scoring ortholog in Drosophila.