Insight into a conserved lifestyle: Protein-carbohydrate adhesion strategies of vector-borne pathogens

Extensive evidence for the role of protein-carbohydrate recognition mechanisms in vector host-pathogen interactions has been unveiled, but growth in this field has been hampered by the lack of molecular tools to study the interface between these two classes of molecules. In addition, other factors have also delayed progress in this field: for example, the general perception that prokaryotic proteins cannot be glycosylated or the assumption that all carbohydrate modifications are similar to those that have been described for mammals. Finally, under-appreciation of the function of glycans beyond cell sorting, protein folding, and simple "decoration" has also contributed to the slowness of progress. To date, the bulk of the research effort in studying protein-carbohydrate interactions between vector-borne pathogens and their host cells remains focused on the vertebrate life stages. Although the protein-carbohydrate recognition theme is, in general, conserved, there is clear evidence of modifications or variations to this theme. The literature suggests that distinct pathogen adhesion domains most likely play different roles depending on the nature of the host cell: vertebrate or invertebrate. Therefore, it may not be appropriate to extrapolate between the two groups of organisms. Despite the variations to the overall theme, one recognition event is clearly conserved across the different vector-borne pathogens. The convergent evolution of several unrelated microbial-pathogen molecules (e.g., CTRP, bacterial lipoproteins, and viral E glycoproteins) with affinity for host cell glycoconjugate polyanion carbohydrates, such as heparan sulfate, is unmistakable. This may in part result from the indistinct requirements for "consensus" heparin binding motifs of proteins. Clusters of six to eight alternating basic amino acid residues have been shown to be the requisite factors for recognition of sulfated polysaccharides (2, 20). Pathogen recognition of glycan receptors represents the first, critical step of a very complex series of events leading to host cell invasion. The evidence suggests that molecular recognition is likely reciprocal, where low-affinity primary attachment to one set of glycoconjugates is strengthened by other coligands and coreceptors from both the pathogen and its host. Inhibiting this initial step by use of conventional methods as well as more novel approaches, such as oligosaccharide mimics or antiglycan antibodies, could result in a reduction in disease transmission. For example, antiglycan antibodies that are taken up by a mosquito along with an parasite infective blood meal can mask parasite glycan receptors that are critical for attachment (27). Clearly, one of the difficulties lies in developing a multivalent inhibitor that can effectively overcome the Velcro-like attachment. While this is no easy task, it is likely that glycobiological analyses will make significant contributions toward resolving the mechanisms of attachment of vector-borne pathogens to their invertebrate hosts.