title: PrgU: a suppressor of sex pheromone toxicity in Enterococcus faecalis.
abstract: Upon sensing of the peptide pheromone cCF10, Enterococcus faecalis cells carrying pCF10 produce three surface adhesins (PrgA, PrgB or Aggregation Substance, PrgC) and the Prg/Pcf type IV secretion system and, in turn, conjugatively transfer the plasmid at high frequencies to recipient cells. Here, we report that cCF10 induction is highly toxic to cells sustaining a deletion of prgU, a small orf located immediately downstream of prgB on pCF10. Upon pheromone exposure, these cells overproduce the Prg adhesins and display impaired envelope integrity, as evidenced by antibiotic susceptibility, misplaced division septa and cell lysis. Compensatory mutations in regulatory loci controlling expression of pCF10-encoded prg/pcf genes, or constitutive PrgU overproduction, block production of the Prg adhesins and render cells insensitive to pheromone. Cells engineered to overproduce PrgB, even independently of other pCF10-encoded proteins, have severely compromised cell envelopes and strong growth defects. PrgU has an RNA-binding fold, and prgB-prgU gene pairs are widely distributed among E. faecalis isolates and other enterococcal and staphylococcal species. Together, our findings support a model in which PrgU proteins represent a novel class of RNA-binding regulators that act to mitigate toxicity accompanying overproduction of PrgB-like adhesins in E. faecalis and other clinically-important Gram-positive species.
authors: Department of Microbiology and Molecular Genetics, McGovern Medical School, 6431 Fannin St, Houston, Texas, 77030, USA.
authors: Minny
authors: M
authors: Bhatty
authors: Department of Microbiology and Molecular Genetics, McGovern Medical School, 6431 Fannin St, Houston, Texas, 77030, USA.
authors: Martha I
authors: MI
authors: Camacho
authors: Department of Microbiology and Molecular Genetics, McGovern Medical School, 6431 Fannin St, Houston, Texas, 77030, USA.
authors: Christian
authors: C
authors: Gonzalez-Rivera
authors: Department of Microbiology and Immunology, University of Minnesota Medical School, Microbiology Research Facility, 689 23rd Ave, S.E, Minneapolis, Minnesota, 55455, USA.
authors: Kristi L
authors: KL
authors: Frank
authors: Department of Microbiology and Immunology, University of Minnesota Medical School, Microbiology Research Facility, 689 23rd Ave, S.E, Minneapolis, Minnesota, 55455, USA.
authors: Jennifer L
authors: JL
authors: Dale
authors: Department of Microbiology and Immunology, University of Minnesota Medical School, Microbiology Research Facility, 689 23rd Ave, S.E, Minneapolis, Minnesota, 55455, USA.
authors: Dawn A
authors: DA
authors: Manias
authors: Department of Microbiology and Immunology, University of Minnesota Medical School, Microbiology Research Facility, 689 23rd Ave, S.E, Minneapolis, Minnesota, 55455, USA.
authors: Gary M
authors: GM
authors: Dunny
authors: Department of Microbiology and Molecular Genetics, McGovern Medical School, 6431 Fannin St, Houston, Texas, 77030, USA.
authors: Peter J
authors: PJ
authors: Christie
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D003227:Conjugation, Genetic / Q000235:genetics; D004269:DNA, Bacterial / Q000378:metabolism; D016983:Enterococcus; D013293:Enterococcus faecalis / Q000235:genetics* / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism*; D010675:Pheromones / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D012724:Sex Attractants / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D015815:Cell Adhesion Molecules; D004269:DNA, Bacterial; D008565:Membrane Proteins; D009842:Oligopeptides; D010675:Pheromones; D012724:Sex Attractants; C057280:peptide pheromone cCF10