The Pseudomonas aeruginosa Two-Component Regulator AlgR Directly ActivatesrsmAExpression in a Phosphorylation-Independent Manner.
Pseudomonas aeruginosais an important pathogen of the immunocompromised, causing both acute and chronic infections. In cystic fibrosis (CF) patients,P. aeruginosacauses chronic disease. The impressive sensory network ofP. aeruginosaallows the bacterium to sense and respond to a variety of stimuli found in diverse environments. Transcriptional regulators, including alternative sigma factors and response regulators, integrate signals changing gene expression, allowingP. aeruginosato cause infection. The two-component transcriptional regulator AlgR is important inP. aeruginosapathogenesis in both acute and chronic infections. In chronic infections, AlgR and the alternative sigma factor AlgU activate the genes responsible for alginate production. Previous work demonstrated that AlgU controlsrsmAexpression. RsmA is a posttranscriptional regulator that is antagonized by two small RNAs, RsmY and RsmZ. In this work, we demonstrate that AlgR directly activatesrsmAexpression from the same promoter as AlgU. In addition, phosphorylation was not necessary for AlgR activation ofrsmAusingalgRandalgZmutant strains. AlgU and AlgR appear to affect the antagonizing small RNAsrsmYandrsmZindirectly. RsmA was active in amucA22mutant strain using leader fusions of two RsmA targets,tssA1andhcnAAlgU and AlgR were necessary for posttranscriptional regulation oftssA1andhcnAAltogether, our work demonstrates that the alginate regulators AlgU and AlgR are important in the control of the RsmA posttranscriptional regulatory system. These findings suggest that RsmA plays an unknown role in mucoid strains due to AlgU and AlgR activities.IMPORTANCEP. aeruginosainfections are difficult to treat and frequently cause significant mortality in CF patients. Understanding the mechanisms of persistence is important. Our work has demonstrated that the alginate regulatory system also significantly impacts the posttranscriptional regulator system RsmA/Y/Z. We demonstrate that AlgR directly activatesrsmAexpression, and this impacts the RsmA regulon. This leads to the possibility that the RsmA/Y/Z system plays a role in helpingP. aeruginosapersist during chronic infection. In addition, this furthers our understanding of the reach of the alginate regulators AlgU and AlgR.
Department of Health Sciences, East Tennessee State University, Johnson City, Tennessee, USA.
Sean D
SD
Stacey
Department of Health Sciences, East Tennessee State University, Johnson City, Tennessee, USA.
Danielle A
DA
Williams
Department of Health Sciences, East Tennessee State University, Johnson City, Tennessee, USA pritchettc@etsu.edu.
Christopher L
CL
Pritchett
AlgR; P. aeruginosa; Pseudomonas aeruginosa; RsmA; cystic fibrosis; mucA; mucoid; two-component regulatory systems