Pseudomonas aeruginosa lasR mutants are associated with cystic fibrosis lung disease progression

Abstract

Background: Pseudomonas aeruginosa with mutations in the transcriptional regulator LasR chronically infect the airways of people with cystic fibrosis (CF), yet the prevalence and clinical implications of lasR mutant infection are unknown.

Methods: In an exploratory study, we screened 166 P. aeruginosa isolates from 58 CF patients for LasR inactivation and mucoidy, and compared clinical characteristics among source patients.

Results: lasR mutation prevalence was comparable to that of mucoidy, the best-described CF-adapted phenotype, but affected patients were on average approximately 2 years younger. In a regression analysis, lung function decline with age was worse among patients with lasR mutant infection than in those without, similar to the effect of mucoidy.

Conclusions: Culture positivity for lasR mutant P. aeruginosa may serve as a marker of early CF adaptive change of prognostic significance. Furthermore, as LasR inactivation alters susceptibility to antibiotics, infection with lasR mutant P. aeruginosa may impact response to therapy.

Figure 1. Characteristic colony morphology identifies lasR mutant P. aeruginosa CF isolates

(a) LB agar-grown colonies of two clonally-related clinical isolates of P. aeruginosa from a single CF patient, one with an inactivating lasR mutation and the other with wild-type lasR, as indicated. The lasR mutant isolate displays phenotypes characteristic of lasR mutants, including surface iridescent, metallic sheen, which is particularly evident in this photograph (yellow arrow). (b) Another pair of LB agar-grown, clonally-related clinical P. aeruginosa isolates in which one isolate has an inactivating lasR mutation that demonstrates colony lysis and flattening (blue arrow). (c) An LB agar-grown P. aeruginosa isolate that is mucoid and has wild-type LasR protein function, for comparison with (d–e). (d) A mucoid P. aeruginosa isolate with an inactivating lasR mutation, exhibiting floating, iridescent material (yellow arrow). (e) Another mucoid isolate with inactivating lasR mutation in which colony lysis is particularly evident (blue arrow).