title: DNA adenine methylase overproduction in Yersinia pseudotuberculosis alters YopE expression and secretion and host immune responses to infection.
abstract: Yersinia pseudotuberculosis mutants that overproduce the DNA adenine methylase (Dam) are highly attenuated, confer fully protective immune responses, and secrete several Yersinia virulence proteins (Yersinia outer proteins [Yops]) under conditions that are nonpermissive for secretion in wild-type strains. We examined here the effects of Dam overproduction on Yersinia virulence determinant expression and secretion, as well as the host immune response to Yersinia antigens. Western blot analysis with convalescent antisera identified several low-calcium-responsive antigens whose synthesis was affected by Dam overproduction. One of these antigens was shown to be the type III secretion effector protein, YopE, a cytotoxin involved in antiphagocytosis. Dam overproduction disrupted both the thermal and calcium regulation of YopE synthesis and relaxed the thermal but not the calcium dependence of YopE secretion. Altered expression and/or secretion of Yersinia proteins in Dam-overproducing strains may contribute to the decreased virulence and heightened immunity observed in vaccinated hosts and may provide a means by which to deliver heterologous antigens and/or immune modulators of the inflammatory response.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California 93106, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Julio
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Heithoff
authors.forename: Robert L
authors.initials: RL
authors.lastname: Sinsheimer
authors.forename: David A
authors.initials: DA
authors.lastname: Low
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mahan
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000032:analysis; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000382:microbiology / Q000473:pathology; D008643:Mesentery; D051379:Mice; D010581:Peyer's Patches / Q000382:microbiology / Q000473:pathology; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000096:biosynthesis / Q000276:immunology*; D015011:Yersinia pseudotuberculosis / Q000201:enzymology* / Q000276:immunology; D015012:Yersinia pseudotuberculosis Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; C063239:yopE protein, Yersinia; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific)