title: The Pseudomonas aeruginosa magnesium transporter MgtE inhibits transcription of the type III secretion system.
abstract: Pseudomonas aeruginosa is an opportunistic pathogen that causes life-long pneumonia in individuals with cystic fibrosis (CF). These long-term infections are maintained by bacterial biofilm formation in the CF lung. We have recently developed a model of P. aeruginosa biofilm formation on cultured CF airway epithelial cells. Using this model, we discovered that mutation of a putative magnesium transporter gene, called mgtE, led to increased cytotoxicity of P. aeruginosa toward epithelial cells. This altered toxicity appeared to be dependent upon expression of the type III secretion system (T3SS). In this study, we found that mutation of mgtE results in increased T3SS gene transcription. Through epistasis analyses, we discovered that MgtE influences the ExsE-ExsC-ExsD-ExsA gene regulatory system of T3SS by either directly or indirectly inhibiting ExsA activity. While variations in calcium levels modulate T3SS gene expression in P. aeruginosa, we found that addition of exogenous magnesium did not inhibit T3SS activity. Furthermore, mgtE variants that were defective for magnesium transport could still complement the cytotoxicity effect. Thus, the magnesium transport function of MgtE does not fully explain the regulatory effects of MgtE on cytotoxicity. Overall, our results indicate that MgtE modulates expression of T3SS genes.
authors.affiliation: Department of Biology, Indiana University-Purdue University Indianapolis, 723 West Michigan St., SL 320, Indianapolis, IN 46202, USA. ga2@iupui.edu
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Anderson
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Yahr
authors.forename: Rustin R
authors.initials: RR
authors.lastname: Lovewell
authors.forename: George A
authors.initials: GA
authors.lastname: O'Toole
mesh_terms: D017920:Antiporters / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D006801:Humans; D026901:Membrane Transport Proteins / Q000096:biosynthesis*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D037521:Virulence Factors / Q000096:biosynthesis*
chemical_list: D017920:Antiporters; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; C092192:MgtE protein, bacteria; D012097:Repressor Proteins; D037521:Virulence Factors