The stage-regulated HASPB and SHERP proteins are essential for differentiation of the protozoan parasite Leishmania major in its sand fly vector, Phlebotomus papatasi

TY - JOUR

T1 - The stage-regulated HASPB and SHERP proteins are essential for differentiation of the protozoan parasite Leishmania major in its sand fly vector, Phlebotomus papatasi

AU - Sadlova, Jovana

AU - Price, Helen P.

AU - Smith, Barbara A.

AU - Votypka, Jan

AU - Volf, Petr

AU - Smith, Deborah F.

N1 - © 2010 Blackwell Publishing Ltd.

PY - 2010/12

Y1 - 2010/12

N2 - The stage-regulated HASPB and SHERP proteins of Leishmania major are predominantly expressed in cultured metacyclic parasites that are competent for macrophage uptake and survival. The role of these proteins in parasite development in the sand fly vector has not been explored, however. Here, we confirm that expression of HASPB is detected only in vector metacyclic stages, correlating with the expression of metacyclic-specific lipophosphoglycan and providing the first definitive protein marker for this infective sand fly stage. Similarly, SHERP is expressed in vector metacyclics but is also detected at low levels in the preceding short promastigote stage. Using genetically modified parasites lacking or complemented for the LmcDNA16 locus on chromosome 23 that contains the HASP and SHERP genes, we further show that the presence of this locus is essential for parasite differentiation to the metacyclic stage in Phlebotomus papatasi. While wild-type and complemented parasites transform normally in late-stage infections, generating metacyclic promastigotes and colonizing the sand fly stomodeal valve, null parasites accumulate at the earlier elongated nectomonad stage of development within the abdominal and thoracic midgut of the sand fly. Complementation with HASPB or SHERP alone suggests that HASPB is the dominant effector molecule in this process.

AB - The stage-regulated HASPB and SHERP proteins of Leishmania major are predominantly expressed in cultured metacyclic parasites that are competent for macrophage uptake and survival. The role of these proteins in parasite development in the sand fly vector has not been explored, however. Here, we confirm that expression of HASPB is detected only in vector metacyclic stages, correlating with the expression of metacyclic-specific lipophosphoglycan and providing the first definitive protein marker for this infective sand fly stage. Similarly, SHERP is expressed in vector metacyclics but is also detected at low levels in the preceding short promastigote stage. Using genetically modified parasites lacking or complemented for the LmcDNA16 locus on chromosome 23 that contains the HASP and SHERP genes, we further show that the presence of this locus is essential for parasite differentiation to the metacyclic stage in Phlebotomus papatasi. While wild-type and complemented parasites transform normally in late-stage infections, generating metacyclic promastigotes and colonizing the sand fly stomodeal valve, null parasites accumulate at the earlier elongated nectomonad stage of development within the abdominal and thoracic midgut of the sand fly. Complementation with HASPB or SHERP alone suggests that HASPB is the dominant effector molecule in this process.

KW - INFECTIVE STAGE

KW - GENE FAMILY

KW - METACYCLIC PROMASTIGOTES

KW - CUTANEOUS LEISHMANIASIS

KW - SURFACE-PROTEINS

KW - EXPRESSION

KW - LIPOPHOSPHOGLYCAN

KW - TRANSMISSION

KW - FLIES

KW - ANTIBODIES

UR - http://www.scopus.com/inward/record.url?scp=78149231890&partnerID=8YFLogxK

U2 - 10.1111/j.1462-5822.2010.01507.x

DO - 10.1111/j.1462-5822.2010.01507.x

M3 - Article

C2 - 20636473

SN - 1462-5814

VL - 12

SP - 1765

EP - 1779

JO - Cellular Microbiology

JF - Cellular Microbiology

IS - 12

ER -