Tropheryma whipplei glycosylation in the pathophysiologic profile of Whipple's disease.
BACKGROUND
Tropheryma whipplei is a bacterium commonly found in people with Whipple's disease, a rare systemic chronic infection. In the present study, we hypothesized that bacterium glycosylation may impair the immune response.


METHODS
Bacterial extracts were analyzed by glycostaining, and reactive proteins, identified by matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectometry, were purified to generate antibodies that could be used in immunofluorescence studies. The reactivity of serum samples obtained from patients and asymptomatic carriers was tested against native or deglycosylated bacteria, for which the fate in macrophages was also investigated.


RESULTS
To our knowledge, we evidenced, for the first time in T. whipplei, a 110-kDa glycoprotein containing sialic acid. This protein, identified as an Wnt1-inducible signaling pathway (WiSP) protein, is associated with periodic acid-Schiff (PAS) staining in infected intramacrophage biofilm. Consistent with the lack of enzymes required for the glycosylation pathway in this bacterium, the glycoproteins disappear during in vitro axenic subcultures, whereas human transcriptome analysis reveals the up-regulation of corresponding genes within infected macrophages. Proteic antigens are not recognized by the serum samples obtained from patients compared with those obtained from nonsick carriers, and T. whipplei that exhibits a low glycosylation profile does not efficiently multiply in macrophages in vitro.


CONCLUSIONS
T. whipplei glycosylation is likely to impair antibody-mediated immune recognition in patients. Such an intracellular antigen masking system in bacteria has not previously been described.
Bonhomme
Cyrille J
CJ
Unite des Rickettsies, Centre National de la Recherche Scientifique 6236, Universite de la Mediterranee, Marseille, France.
Renesto
Patricia
P
Desnues
Benoît
B
Ghigo
Eric
E
Lepidi
Hubert
H
Fourquet
Patrick
P
Fenollar
Florence
F
Henrissat
Bernard
B
Mege
Jean-Louis
JL
Raoult
Didier
D
D018441:Biofilms; D050260:Carbohydrate Metabolism; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D011499:Protein Processing, Post-Translational; D054851:Tropheryma / Q000378:metabolism*; D008061:Whipple Disease / Q000276:immunology / Q000382:microbiology*
D006023:Glycoproteins