The Leishmania major BBSome subunit BBS1 is essential for parasite virulence in the mammalian host

Price, H. P., Paape, D. , Hodgkinson, M. R., Farrant, K., Doehl, J., Stark, M. and Smith, D. F. (2013) The Leishmania major BBSome subunit BBS1 is essential for parasite virulence in the mammalian host. Molecular Microbiology, 90(3), pp. 597-611. (doi: 10.1111/mmi.12383) (PMID:23998526) (PMCID:PMC3916885)

Abstract

Bardet–Biedl syndrome (BBS) is a human genetic disorder with a spectrum of symptoms caused by primary cilium dysfunction. The disease is caused by mutations in one of at least 17 identified genes, of which seven encode subunits of the BBSome, a protein complex required for specific trafficking events to and from the primary cilium. The molecular mechanisms associated with BBSome function remain to be fully elucidated. Here, we generated null and complemented mutants of the BBSome subunit BBS1 in the protozoan parasite, Leishmania. In the absence of BBS1, extracellular parasites have no apparent defects in growth, flagellum assembly, motility or differentiation in vitro but there is accumulation of vacuole-like structures close to the flagellar pocket. Infectivity of these parasites for macrophages in vitro is reduced compared with wild-type controls but the null parasites retain the ability to differentiate to the intracellular amastigote stage. However, infectivity of BBS1 null parasites is severely compromised in a BALB/c mouse footpad model. We hypothesize that the absence of BBS1 in Leishmania leads to defects in specific trafficking events that affect parasite persistence in the host. This is the first report of an association between the BBSome complex and pathogen infectivity.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Paape, Dr Daniel
• Authors: Price, H. P., Paape, D., Hodgkinson, M. R., Farrant, K., Doehl, J., Stark, M., and Smith, D. F.
• Subjects: Q Science > Q Science (General)
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Molecular Microbiology
• Publisher: Wiley-Blackwell Publishing Ltd
• ISSN: 0950-382X
• ISSN (Online): 1365-2958
• Copyright Holders: Copyright © 2013 The Authors
• First Published: First published in Molecular Microbiology 90(3):597-611
• Publisher Policy: Reproduced under a Creative Commons License