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closeReferee Comments: Referee 1
Posted by PLOS_ONE_Group on 04 Jun 2007 at 22:57 GMT
Reviewer 1's Review
“The title of the manuscript indicates a role of the DBL domain of Pf332 in rosetting of late stages parasites. In addition, the authors show inhibition of merozoite invasion using anti DBL-nonDBL antibodies.
Despite the revision, there is still no convincing evidence to claim that this molecule is exposed in late stages and is able to form rosettes. The DBL domain is protease resistant at high doses (1 mg/ml), which makes it rather unlikely to be surface exposed. It would be important for the authors to show that the DBL-transfected CHO cell rosetting is also protease resistant.
Rosette-formation should be documented using images of late stage cultures and statistical values for number of rosettes per infected erythrocyte given. Ideally, this should be done under shear stress using flow adhesion chambers to demonstrate this adhesion phenotype under physiologically relevant conditions.
Even if the rosetting part is not yet convincing, the work is of interest and it may be sufficient to re-orientate the manuscript in a different way using an alternative title such as: "A novel erythrocyte DBL binding domain in the Pf332 molecule of P. falciparum". This would leave the option that the biological function of erythrocyte adhesion is after erythrocyte rupture. Thus, describing the data in a more neutral way and being less dogmatic about the role of the DBL domain in rosetting of late stages (unless better data can be provided) may solve the problem. A speculative schematic model may be presented in the discussion section.”
N.B. These are the general comments made by the reviewer when reviewing this paper in light of which the manuscript was revised. Specific points addressed during revision of the paper are not shown.