title: An allele of an ancestral transcription factor dependent on a horizontally acquired gene product.
abstract: Changes in gene regulatory circuits often give rise to phenotypic differences among closely related organisms. In bacteria, these changes can result from alterations in the ancestral genome and/or be brought about by genes acquired by horizontal transfer. Here, we identify an allele of the ancestral transcription factor PmrA that requires the horizontally acquired pmrD gene product to promote gene expression. We determined that a single amino acid difference between the PmrA proteins from the human adapted Salmonella enterica serovar Paratyphi B and the broad host range S. enterica serovar Typhimurium rendered transcription of PmrA-activated genes dependent on the PmrD protein in the former but not the latter serovar. Bacteria harboring the serovar Typhimurium allele exhibited polymyxin B resistance under PmrA- or under PmrA- and PmrD-inducing conditions. By contrast, isogenic strains with the serovar Paratyphi B allele displayed PmrA-regulated polymyxin B resistance only when experiencing activating conditions for both PmrA and PmrD. We establish that the two PmrA orthologs display quantitative differences in several biochemical properties. Strains harboring the serovar Paratyphi B allele showed enhanced biofilm formation, a property that might promote serovar Paratyphi B's chronic infection of the gallbladder. Our findings illustrate how subtle differences in ancestral genes can impact the ability of horizontally acquired genes to confer new properties.
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri, United States of America.
authors.forename: H Deborah
authors.initials: HD
authors.lastname: Chen
authors.forename: Mollie W
authors.initials: MW
authors.lastname: Jewett
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Groisman
mesh_terms: D000483:Alleles; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D022761:Gene Transfer, Horizontal; D006801:Humans; D011112:Polymyxin B / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D019779:Salmonella enterica / Q000187:drug effects / Q000235:genetics; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; C087732:PmrD protein, Salmonella; C081902:pmrA protein, Bacteria; D011112:Polymyxin B