title: Antibiotic treatment of Pseudomonas aeruginosa biofilms stimulates expression of the magnesium transporter gene mgtE.
abstract: Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen with the capacity to cause serious disease, including chronic biofilm infections in the lungs of cystic fibrosis (CF) patients. These infections are treated with high concentrations of antibiotics. Virulence modulation is an important tool utilized by P. aeruginosa to propagate infection and biofilm formation in the CF airway. Many different virulence modulatory pathways and proteins have been identified, including the magnesium transporter protein MgtE. We have recently found that isogenic deletion of mgtE leads to increased cytotoxicity through effects on the type III secretion system. To explore the role of the CF lung environment in MgtE activity, we investigated mgtE transcriptional regulation following antibiotic treatment. Utilizing quantitative real-time-PCR, we have demonstrated an increase in mgtE transcript levels following antibiotic treatment with most of the 12 antibiotics tested. To begin to determine the regulatory network governing mgtE expression, we screened a transposon-mutant library of P. aeruginosa to look for mutants with potentially altered mgtE activity, using cytotoxicity as a readout. In this screen, we observed that AlgR, which regulates production of the biofilm polysaccharide alginate, alters MgtE-mediated cytotoxicity. This cross-talk between MgtE and AlgR suggests that AlgR is involved in linking external inducing signals (e.g. antibiotics) to mgtE transcription and downstream virulence and biofilm activities. Analysing such interactions may lead to a better understanding of how the CF lung environment shapes P. aeruginosa biofilm infections.
authors.affiliation: Department of Biology, Butler University, Indianapolis, IN 46208, USA.|Department of Biology, IUPUI, Indianapolis, IN 46202, USA.
authors.forename: Carly V
authors.initials: CV
authors.lastname: Redelman
authors.affiliation: Department of Biology, IUPUI, Indianapolis, IN 46202, USA.
authors.forename: Shubham
authors.initials: S
authors.lastname: Chakravarty
authors.affiliation: Department of Biology, IUPUI, Indianapolis, IN 46202, USA.
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Anderson
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017920:Antiporters / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival; D004251:DNA Transposable Elements; D004847:Epithelial Cells / Q000382:microbiology / Q000502:physiology; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D053263:Gene Regulatory Networks; D006801:Humans; D016254:Mutagenesis, Insertional; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: C110681:AlgR protein, Pseudomonas aeruginosa; D000900:Anti-Bacterial Agents; D017920:Antiporters; D001426:Bacterial Proteins; D004251:DNA Transposable Elements; C092192:MgtE protein, bacteria; D015534:Trans-Activators