The antiretroviral lectin cyanovirin-N targets well-known and novel targets on the surface of Entamoeba histolytica trophozoites.
Entamoeba histolytica, the protist that causes amebic dysentery and liver abscess, has a truncated Asn-linked glycan (N-glycan) precursor composed of seven sugars (Man(5)GlcNAc(2)). Here, we show that glycoproteins with unmodified N-glycans are aggregated and capped on the surface of E. histolytica trophozoites by the antiretroviral lectin cyanovirin-N and then replenished from large intracellular pools. Cyanovirin-N cocaps the Gal/GalNAc adherence lectin, as well as glycoproteins containing O-phosphodiester-linked glycans recognized by an anti-proteophosphoglycan monoclonal antibody. Cyanovirin-N inhibits phagocytosis by E. histolytica trophozoites of mucin-coated beads, a surrogate assay for amebic virulence. For technical reasons, we used the plant lectin concanavalin A rather than cyanovirin-N to enrich secreted and membrane proteins for mass spectrometric identification. E. histolytica glycoproteins with occupied N-glycan sites include Gal/GalNAc lectins, proteases, and 17 previously hypothetical proteins. The latter glycoproteins, as well as 50 previously hypothetical proteins enriched by concanavalin A, may be vaccine targets as they are abundant and unique. In summary, the antiretroviral lectin cyanovirin-N binds to well-known and novel targets on the surface of E. histolytica that are rapidly replenished from large intracellular pools.
Carpentieri
Andrea
A
Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, MA 02118, USA.
Ratner
Daniel M
DM
Ghosh
Sudip K
SK
Banerjee
Sulagna
S
Bushkin
G Guy
GG
Cui
Jike
J
Lubrano
Michael
M
Steffen
Martin
M
Costello
Catherine E
CE
O'Keefe
Barry
B
Robbins
Phillips W
PW
Samuelson
John
J
D000563:Amebicides / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D044966:Anti-Retroviral Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000494:pharmacology*; D002352:Carrier Proteins / Q000494:pharmacology*; D004404:Dysentery, Amebic / Q000209:etiology / Q000469:parasitology; D004748:Entamoeba histolytica / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008101:Liver Abscess, Amebic / Q000209:etiology / Q000469:parasitology; D037241:Mannose-Binding Lectins / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010587:Phagocytosis / Q000187:drug effects; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D053058:Trophozoites / Q000187:drug effects / Q000378:metabolism; D014774:Virulence / Q000187:drug effects
D000563:Amebicides; D044966:Anti-Retroviral Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D006023:Glycoproteins; D037241:Mannose-Binding Lectins; D015800:Protozoan Proteins; C107733:cyanovirin N