Abstract
Bacterial vaginosis is a genital tract infection, thought to be caused by transformation of a lactobacillus-rich flora to a dysbiotic microbiota enriched in mixed anaerobes. The most prominent of these is Gardnerella vaginalis (GV), an anaerobic pathogen that produces sialidase enzyme to cleave terminal sialic acid residues from human glycans. Notably, high sialidase activity is associated with preterm birth and low birthweight. We explored the potential of the sialidase inhibitor Zanamavir against GV whole cell sialidase activity using methyl–umbelliferyl neuraminic acid (MU-NANA) cleavage assays, with Zanamavir causing a 30% reduction in whole cell GV sialidase activity (p < 0.05). Furthermore, cellular invasion assays using HeLa cervical epithelial cells, infected with GV, demonstrated that Zanamivir elicited a 50% reduction in cell association and invasion (p < 0.05). Our data thus highlight that pharmacological sialidase inhibitors are able to modify BV-associated sialidase activity and influence host–pathogen interactions and may represent novel therapeutic adjuncts.
Highlights
Bacterial vaginosis (BV) is a prevalent condition characterised by vaginal irritation and malodour
Sialidase assays examined if bacterial sialidase activity could be directly inhibited by the sialidase inhibitor Zanamivir, marketed as R elenza®
We established that Zanamivir reduces two facets of the virulence of the BV-associated pathogen G. vaginalis, namely, its sialidase activity and ability to invade Human cells
Summary
Bacterial vaginosis (BV) is a prevalent condition characterised by vaginal irritation and malodour. One prominent trait of the dysbiotic microbiota in BV is production of high levels of sialidase enzymes produced by bacteria that act to release sialic acid, the terminal glycan on many glycoproteins in secretions and on mucosal cell surfaces- including vaginal mucous (Severi et al 2007; Stafford et al 2011; Lewis et al 2012; Hardy et al 2017). This sialic acid is used by pathogens as a mechanism of adherence to cellular and inert surfaces, as a source of nutrition and modifies the normal mucus barrier and immune response (Amith et al 2009, 2010; Stafford et al 2011; Lewis et al 2012, 2013; Vick et al 2014). Evidence suggests BV in conjunction with high sialidase activity is predictive of PTB and low birthweight, while BV alone is not (Cauci et al 2005)
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