title: Inheritance of the lysozyme inhibitor Ivy was an important evolutionary step by Yersinia pestis to avoid the host innate immune response.
abstract: BACKGROUND
  Yersinia pestis (the plague bacillus) and its ancestor, Yersinia pseudotuberculosis (which causes self-limited bowel disease), encode putative homologues of the periplasmic lysozyme inhibitor Ivy and the membrane-bound lysozyme inhibitor MliC. The involvement of both inhibitors in virulence remains subject to debate.
  
  
  METHODS
  Mutants lacking ivy and/or mliC were generated. We evaluated the mutants' ability to counter lysozyme, grow in serum, and/or counter leukocytes; to produce disease in wild-type, neutropenic, or lysozyme-deficient rodents; and to induce host inflammation.
  
  
  RESULTS
  MliC was not required for lysozyme resistance and the development of plague. Deletion of ivy decreased Y. pestis' ability to counter lysozyme and polymorphonuclear neutrophils, but it did not affect the bacterium's ability to grow in serum or resist macrophages. Y. pestis lacking Ivy had attenuated virulence, unless animals were neutropenic or lysozyme deficient. The Ivy mutant induced inflammation to a degree similar to that of the parental strain. Last, Y. pseudotuberculosis did not require Ivy to counter lysozyme and for virulence.
  
  
  CONCLUSIONS
  Ivy is required to counter lysozyme during infection, but its role as a virulence factor is species dependent. Our study also shows that a gene that is not necessary for the virulence of an ancestral bacterium may become essential in the emergence of a new pathogen.
authors: Equipe Peste et Yersinia pestis, INSERM U1019, Paris, France.
authors: Anne
authors: A
authors: Derbise
authors: François
authors: F
authors: Pierre
authors: Maud
authors: M
authors: Merchez
authors: Elizabeth
authors: E
authors: Pradel
authors: Sabrina
authors: S
authors: Laouami
authors: Isabelle
authors: I
authors: Ricard
authors: Jean-Claude
authors: JC
authors: Sirard
authors: Jill
authors: J
authors: Fritz
authors: Nadine
authors: N
authors: Lemaître
authors: Henry
authors: H
authors: Akinbi
authors: Ivo G
authors: IG
authors: Boneca
authors: Florent
authors: F
authors: Sebbane
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001769:Blood / Q000276:immunology / Q000382:microbiology; D002417:Cattle; D002460:Cell Line; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development; D019143:Evolution, Molecular; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009113:Muramidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism / Q000382:microbiology; D019897:Periplasm / Q000737:chemistry; D010586:Phagocytes / Q000378:metabolism / Q000382:microbiology; D010930:Plague / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051381:Rats; D011914:Rats, Inbred BN; D012710:Serum Albumin, Bovine / Q000737:chemistry; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism; D015010:Yersinia pestis / Q000235:genetics / Q000472:pathogenicity*; D015011:Yersinia pseudotuberculosis / Q000235:genetics / Q000472:pathogenicity; D015012:Yersinia pseudotuberculosis Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; D012710:Serum Albumin, Bovine; D009113:Muramidase