title: Reciprocal control between a bacterium's regulatory system and the modification status of its lipopolysaccharide.
abstract: Gram-negative bacteria often modify their lipopolysaccharide (LPS), thereby increasing resistance to antimicrobial agents and avoidance of the host immune system. However, it is unclear how bacteria adjust the levels and activities of LPS-modifying enzymes in response to the modification status of their LPS. We now address this question by investigating the major regulator of LPS modifications in Salmonella enterica. We report that the PmrA/PmrB system controls expression of a membrane peptide that inhibits the activity of LpxT, an enzyme responsible for increasing the LPS negative charge. LpxT's inhibition and the PmrA-dependent incorporation of positively charged L-4-aminoarabinose into the LPS decrease Fe(3+) binding to the bacterial cell. Because Fe(3+) is an activating ligand for the sensor PmrB, transcription of PmrA-dependent LPS-modifying genes is reduced. This mechanism enables bacteria to sense their cell surface by its effect on the availability of an inducing signal for the system regulating cell-surface modifications.
authors.affiliation: Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Akinori
authors.initials: A
authors.lastname: Kato
authors.forename: H Deborah
authors.initials: HD
authors.lastname: Chen
authors.forename: Tammy
authors.initials: T
authors.lastname: Latifi
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Groisman
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001089:Arabinose / Q000031:analogs & derivatives / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D005290:Ferric Compounds / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D008070:Lipopolysaccharides / Q000378:metabolism*; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005290:Ferric Compounds; D008070:Lipopolysaccharides; C409039:PmrB protein, bacteria; D014157:Transcription Factors; C016982:aminoarabinose; C081902:pmrA protein, Bacteria; D001089:Arabinose; D017856:Phosphotransferases (Phosphate Group Acceptor)