Drosophila has been used extensively to model infection by Pseudomonas aeruginosa, a major cause of opportunistic human infection and one of the most common pathogens isolated from patients who have been hospitalized. Immunocompromised individuals are at particular risk; chronic lung infections of P. aeruginosa can develop in sufferers of cystic fibrosis. Antimicrobial resistance is common in P. aeruginosa, making it difficult to treat.
P. aeruginosa is inoculated into flies by abdominal prick or oral ingestion (methods described in FBrf0208654). Experiments using flies as the host have been used to characterize the function and interactions of P. aeruginosa genes. Among these, P. aeruginosa virulence genes have been investigated, however, it has been discovered that many of its virulence determinants are host-specific. Interactions between P. aeruginosa virulence factors and components of Drosophila innate immunity response have been characterized; components of the Toll signaling pathway play a role. A UAS construct carrying the GTPase-activating domain of the P. aeruginosa gene encoding the ExoS toxin (Paer\ExoS) has been introduced into flies.
Work in flies has contributed to characterization of P. aeruginosa quorum-sensing (QS) signaling molecules and biofilm formation; these processes pertain to long-term persistence in cystic fibrosis patients, resulting in chronic lung infection. The human gene for the enzyme paraoxonase 1, Hsap\PON1, has introduced into flies; PON1 degrades the acyl-homoserine lactones (AHLs) that serve as quorum-sensing signaling molecules, and may offer a mechanism for treatment.
[updated Mar. 2021 by FlyBase; FBrf0222196]
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)
Serious Pseudomonas infections usually occur in people in the hospital and/or with weakened immune systems. Infections of the blood, pneumonia, and infections following surgery can lead to severe illness and death. Healthy people can also develop mild illnesses with Pseudomonas aeruginosa, especially after exposure to water. Ear infections, especially in children, and more generalized skin rashes may occur after exposure to inadequately chlorinated hot tubs or swimming pools. Eye infections have occasionally been reported in persons using extended-wear contact lenses. (https://www.cdc.gov/hai/organisms/pseudomonas.html#types)
Pseudomonas infections are considered opportunistic infections, causing disease when a person's immune system is already impaired. Conditions that may increase the risk of infection include: burn wounds, receiving chemotherapy for cancer, cystic fibrosis, HIV or AIDS, presence of a foreign body, like a mechanical ventilator or catheter, undergoing an invasive procedure, like a surgery. Infections can be severe in people whose immune systems are already compromised. (https://www.healthline.com/health/pseudomonas-infections#risk-factors)
Pseudomonas aeruginosa has an extremely broad spectrum of virulence: in addition to being a major cause of opportunistic human infection, it has been shown to be virulent toward plants, insects, and C. elegans (FBrf0132363 and references cited therein).
Antimicrobial resistance is common in P. aeruginosa, making it difficult to treat; antimicrobial resistance is categorized as intrinsic, acquired, or adaptive (Azam and Khan, 2018; pubmed:30036575).
Using small signaling molecules called acyl-homoserine lactones (AHLs), populations of P. aeruginosa can coordinate phenotypic changes, including biofilm formation and virulence factor secretion. This concentration-dependent process is called quorum sensing (QS). Interference with QS has been identified as a potential source of new treatments for P. aeruginosa infection. (FBrf0210217 and references cited therein).
Changes resulting from quorum sensing, such as biofilm formation, reduce acute virulence and promote chronic infection.
Formation of biofilms enhance the ability to cause infections by protecting bacteria from host defenses and chemotherapy (Mulcahy et al., 2014; pubmed:24096885).
No gene orthologous to PON1 has been identified in Drosophila.
