Oligopeptidase B deficient mutants of Leishmania major

Jane C. Munday, Karen McLuskey, Elaine Brown, Graham H Coombs, Jeremy C Mottram

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Oligopeptidase B is a clan SC, family S9 serine peptidase found in gram positive bacteria, plants and try-panosomatids. Evidence suggests it is a virulence factor and thus therapeutic target in both Trypanosome cruzi and T. brucei, but little is known about its function in Leishmania. In this study L major OPB-deficient mutants (Delta opb) 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 Delta opb was investigated via by mapping its sequence onto the 1.6 angstrom 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. (C) 2010 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)49-57
Number of pages9
JournalMolecular and Biochemical Parasitology
Volume175
Issue number1
DOIs
Publication statusPublished - Jan 2011

Fingerprint

oligopeptidase B
Leishmania major
Trypanosomiasis
Leishmania
Virulence Factors
Gram-Positive Bacteria
Enzymes
Substrate Specificity
Serine
Peptide Hydrolases
Macrophages
Therapeutics

Keywords

  • Leishmania
  • Peptidase
  • Virulence
  • Oligopeptidase

Cite this

Munday, Jane C. ; McLuskey, Karen ; Brown, Elaine ; Coombs, Graham H ; Mottram, Jeremy C. / Oligopeptidase B deficient mutants of Leishmania major. In: Molecular and Biochemical Parasitology. 2011 ; Vol. 175, No. 1. pp. 49-57.
@article{f1a4ba8bd5554ee489ff592a581ae0c4,
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 try-panosomatids. Evidence suggests it is a virulence factor and thus therapeutic target in both Trypanosome cruzi and T. brucei, but little is known about its function in Leishmania. In this study L major OPB-deficient mutants (Delta opb) 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 Delta opb was investigated via by mapping its sequence onto the 1.6 angstrom 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. (C) 2010 Elsevier B.V. All rights reserved.",
keywords = "Leishmania, Peptidase, Virulence, Oligopeptidase",
author = "Munday, {Jane C.} and Karen McLuskey and Elaine Brown and Coombs, {Graham H} and Mottram, {Jeremy C}",
note = "Copyright {\circledC} 2010 Elsevier B.V. All rights reserved.",
year = "2011",
month = "1",
doi = "10.1016/j.molbiopara.2010.09.003",
language = "English",
volume = "175",
pages = "49--57",
journal = "Molecular and Biochemical Parasitology",
issn = "0166-6851",
number = "1",

}

Oligopeptidase B deficient mutants of Leishmania major. / Munday, Jane C.; McLuskey, Karen; Brown, Elaine; Coombs, Graham H; Mottram, Jeremy C.

In: Molecular and Biochemical Parasitology, Vol. 175, No. 1, 01.2011, p. 49-57.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Oligopeptidase B deficient mutants of Leishmania major

AU - Munday, Jane C.

AU - McLuskey, Karen

AU - Brown, Elaine

AU - Coombs, Graham H

AU - Mottram, Jeremy C

N1 - Copyright © 2010 Elsevier B.V. All rights reserved.

PY - 2011/1

Y1 - 2011/1

N2 - Oligopeptidase B is a clan SC, family S9 serine peptidase found in gram positive bacteria, plants and try-panosomatids. Evidence suggests it is a virulence factor and thus therapeutic target in both Trypanosome cruzi and T. brucei, but little is known about its function in Leishmania. In this study L major OPB-deficient mutants (Delta opb) 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 Delta opb was investigated via by mapping its sequence onto the 1.6 angstrom 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. (C) 2010 Elsevier B.V. All rights reserved.

AB - Oligopeptidase B is a clan SC, family S9 serine peptidase found in gram positive bacteria, plants and try-panosomatids. Evidence suggests it is a virulence factor and thus therapeutic target in both Trypanosome cruzi and T. brucei, but little is known about its function in Leishmania. In this study L major OPB-deficient mutants (Delta opb) 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 Delta opb was investigated via by mapping its sequence onto the 1.6 angstrom 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. (C) 2010 Elsevier B.V. All rights reserved.

KW - Leishmania

KW - Peptidase

KW - Virulence

KW - Oligopeptidase

UR - http://www.scopus.com/inward/record.url?scp=78049435989&partnerID=8YFLogxK

U2 - 10.1016/j.molbiopara.2010.09.003

DO - 10.1016/j.molbiopara.2010.09.003

M3 - Article

VL - 175

SP - 49

EP - 57

JO - Molecular and Biochemical Parasitology

JF - Molecular and Biochemical Parasitology

SN - 0166-6851

IS - 1

ER -