Rise in frequency oflasRmutantPseudomonas aeruginosaamong keratitis isolates between 1993 and 2021

Abstract

ABSTRACTPseudomonas aeruginosacauses severe vision threatening keratitis. LasR is a transcription factor that regulates virulence associated genes in response to the quorum sensing molecule N-3-oxo-dodecanoyl-L-homoserine lactone.P. aeruginosaisolates withlasRmutations are characterized by an iridescent high sheen phenotype caused by a build-up of 2-heptyl-4-quinolone. A previous study indicated a high proportion (22 out of 101) ofP. aeruginosakeratitis isolates from India between 2010 and 2016 were sheen positive and had mutations in thelasRgene, and the sheen phenotype correlated with worse clinical outcomes for patients. In this study, a longitudinal collection ofP. aeruginosakeratitis isolates from Eastern North America were screened forlasRmutations by the sheen phenotype and sequencing of thelasRgene. A significant increase in the frequency of isolates with the sheen positive phenotype was observed in isolates between 1993 and 2021. Extracellular protease activity was lower among the sheen positive isolates and a definedlasRmutant. ClonedlasRalleles from the sheen positive isolates were loss of function or dominant negative and differed in sequence from previously reported ocularlasRmutant alleles. Insertion elements were present in a subset of independent isolates and may represent an endemic source from some of the isolates. Retrospective analysis of patient information suggested significantly better visual outcomes for patients with infected by sheen positive isolates. Together, these results indicate an increasing trend towardslasRmutations among keratitis isolates at a tertiary eye care hospital in the United States.