New tools to monitorPseudomonas aeruginosainfection and biofilmsin vivoinC. elegans

Abstract

AbstractAntimicrobial resistance is a growing health problem.Pseudomonas aeruginosais a pathogen of major concern because of its multidrug resistance and global threat, especially in health-care settings. The pathogenesis and drug resistance ofP. aeruginosadepends on its ability to form biofilms, making infections chronic and untreatable as the biofilm protects against antibiotics and host immunity. A major barrier to developing new antimicrobials is the lack ofin vivobiofilm models. Standard microbiological testing is usually performedin vitrousing planktonic bacteria, without representation of biofilms, reducing translatability. Here we develop tools to study both infection and biofilm formation byP. aeruginosa in vivoto accelerate development of strategies targeting infection and pathogenic biofilms. Using the nematodeCaenorhabditis elegansandP. aeruginosareporters combined within vivoimaging we show that fluorescentP. aeruginosareporters that form biofilmsin vitrocan be used to visualise tissue infection. Using automated tracking ofC. elegansmovement, we find that that the timing of this infection corresponds with a decline in health endpoints. In a mutant strain ofP. aeruginosalacking RhlR, a transcription factor that controls quorum sensing and biofilm formation, we find reduced capacity ofP. aeruginosato form biofilms, invade host tissues and negatively impact healthspan and survival. Our findings suggest that RhlR could be a new antimicrobial target to reduceP. aeruginosabiofilms and virulencein vivoandC. eleganscould be used to more effectively screen for new drugs to combat antimicrobial resistance.