title: Oligopeptidase B deficient mutants of Leishmania major.
abstract: Oligopeptidase B is a clan SC, family S9 serine peptidase found in gram positive bacteria, plants and trypanosomatids. Evidence suggests it is a virulence factor and thus therapeutic target in both Trypanosoma cruzi and T. brucei, but little is known about its function in Leishmania. In this study L. major OPB-deficient mutants (Δopb) were created. These grew normally as promastigotes, had a small deficiency in their ability to undergo differentiation to metacyclic promastigotes, were significantly less able to infect and survive within macrophages in vitro, but were virulent to mice. These data suggest that L. major OPB itself is not an important virulence factor, indicating functional differences between trypanosomes and Leishmania in their interaction with the mammalian host. The possibility that an OPB-like enzyme (designated OPB2) in L. major might compensate for the loss of OPB in Δopb was investigated via by mapping its sequence onto the 1.6Å structure of L. major OPB. This suggested that the residues involved in the S1 and S2 subsites of OPB2 are identical to OPB and hence the substrate specificity would be similar. Consequently there may be redundancy between the two enzymes.
authors.affiliation: Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, Scotland, UK.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Munday
authors.forename: Karen
authors.initials: K
authors.lastname: McLuskey
authors.forename: Elaine
authors.initials: E
authors.lastname: Brown
authors.forename: Graham H
authors.initials: GH
authors.lastname: Coombs
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Mottram
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D017353:Gene Deletion; D018320:Leishmania major / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000469:parasitology / Q000473:pathology; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000235:genetics; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000172:deficiency* / Q000235:genetics; D037521:Virulence Factors / Q000172:deficiency / Q000235:genetics
chemical_list: D015800:Protozoan Proteins; D037521:Virulence Factors; D012697:Serine Endopeptidases; C090703:oligopeptidase B