Drosophila melanogaster as an organism model for studying cystic fibrosis and its major associated microbial infections

Abstract

Cystic fibrosis (CF) is a human genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene that encodes a chloride channel. The most severe clinical manifestation is associated with chronic pulmonary infections by pathogenic and opportunistic microbes. Drosophila melanogaster has become the invertebrate model of choice for modeling microbial infections and studying the induced innate immune response. Here, we review its contribution to the understanding of infections with six major pathogens associated with CF ( Staphylococcus aureus , Pseudomonas aeruginosa , Burkholderia cepacia , Mycobacterium abscessus , Streptococcus pneumoniae, and Aspergillus fumigatus ) together with the perspectives opened by the recent availability of two CF models in this model organism.

The utility of Drosophila melanogaster as a fungal infection model

“…Drosophila , affectionately dubbed the biology “work horse”, has been used in fundamental biology, inbreeding and heredity studies since the early 1900s ( 27 , 31 ) and has led to substantial contributions to our understanding of genetics, cellular biology, neurobiology and immunology ( 31 , 32 ). Of note, the discovery of Drosophila Toll receptor nearly 3 decades ago elucidated the function of the analogous mammalian Toll-like receptor (TLR) pathway, which is indispensable to innate immunity ( 20 ; Lemaitre, 21 , 26 ).…”

“…AMPs are small, positively charged peptides that interact with hydrophobic regions of microbial cells walls and cause cell wall degradation and microbial death and are secreted into the haemolymph by the fat body ( 45 , 46 ). In addition to AMPs, reactive oxygen species (ROS) are produced by Dual Oxidase (DUOX) and NADPH (Nox) at the epithelial cells ( 26 , 32 ). The humoral response also provides protection against viral attack through RNAi and autophagy processes ( 36 , 47 ).…”

“…The WHO classified Cryptococcus neoformans , A. fumigatus , C. albicans , and the recently emerged C. auris as “Critical” pathogens. A. fumigatus is a filamentous, airborne pathogen that causes invasive aspergillosis, in vulnerable populations, like cystic fibrosis patients ( 32 , 84 ). Drosophila has been used to study A. fumigatus pathogenesis since as far back as 2005 ( 85 , 86 ).…”