Purpose of review
Here, we review recent progress made on the genetic characterization of
Giardia duodenalis
assemblages and their relationship with virulence. We also discuss the implications of virulence factors in the pathogenesis of giardiasis, and advances in the development of vaccines and drugs based on knowledge of virulence markers.
Recent findings
The use of transcriptomic and proteomic technologies as well as whole genome sequencing (WGS) from single cysts has allowed the assembly of the draft genome sequences for assemblages C and D of
G. duodenalis
. These findings, along with the published genomes for assemblages A, B, and E, have allowed comparative genomic investigations. In addition, the use of these methodologies for the characterization of the secretomes of trophozoite-epithelial cell interactions for assemblages A/B has led to the identification of virulence markers including energy metabolism enzymes, proteinases, high-cysteine membrane proteins (HCMPs), and variant surface proteins (VSPs). Recently, some drugs and vaccines, targeting virulence factors have been developed, offering possible alternatives to current treatment and prevention options against giardiasis.
Summary
Among the nine recognized species of
Giardia
,
G. duodenalis
stands out because of its broad spectrum of hosts and its socio-economic importance. This species comprises eight genetic assemblages (A to H), of which A and B are zoonotic, and the other assemblages have narrow host specificities. Assemblages A and B may be considered as the most virulent ones, but the existence of asymptomatic carriers and considerable genetic variability within and among these assemblages hampers the definition of common virulence factors. The attachment of
Giardia
trophozoites to epithelial cells and structural cytoskeleton components of the adhesive disk, such as giardins or tubulins, is proposed to play key roles, but toxins have not yet been precisely defined. However, recent transcriptomic and proteomic analyses of the secretomes of trophozoites representing assemblages A and B and interacting with particular epithelial cell lines have defined a series of virulence factors, including glycolytic (e.g., enolase) and arginolytic (e.g., arginine deiminase) enzymes, cysteine proteases (e.g., giardipain-1) and VSPs (e.g., VSP9B10A). Other factors, such as HCMPs and tenascins, have been consistently found to be excreted/secreted, but their role(s) in the pathogenesis of giardiasis has not yet been elucidated. Interestingly, recent investigations of single cysts representing assemblages C and D using advanced sequencing and informatic methods have suggested that the transcription/expression profiles of virulence factors vary both within and between assemblages, thus assemblage-specific molecules might allow adaptation to the microenviron...
