Microbiome Composition Regulates Cathepsin Expression in Vaginal Fluid Across BV Diagnoses and Community State Types

Area of Science:

• Microbiology
• Biochemistry
• Reproductive Health

Background:

• Bacterial vaginosis (BV) is linked to vaginal microbiome disruption and extracellular matrix (ECM) remodeling.
• The role of host proteases, specifically cathepsins, in BV-associated ECM remodeling is not well understood.
• Understanding cathepsin involvement may reveal mechanisms underlying BV and its reproductive health implications.

Purpose of the Study:

• To investigate differences in the expression and activity of cathepsins K, L, S, and V in relation to BV diagnosis and vaginal community state types (CSTs).
• To test the hypothesis that BV and associated CSTs exhibit increased expression and activity of collagen and elastin-degrading cathepsins.

Main Methods:

• Vaginal fluid samples were analyzed for BV diagnosis and CST classification.
• Cathepsin expression (inactive and active forms) was assessed using Western blotting.
• Proteolytic activity was measured via multiplex cathepsin zymography.
• Statistical analyses, including principal component analysis and linear regression, explored associations between cathepsin activity, microbial diversity, and CST.

Main Results:

• Procathepsin K expression was elevated in BV-positive and CST IV samples; total cathepsin L expression increased in Nugent-intermediate samples.
• Cathepsins S and V showed varied expression patterns in inactive/active forms across Nugent-intermediate and CST III samples.
• Overall cathepsin activity, including cathepsins K and V, did not significantly differ between BV diagnoses or CSTs, indicating individual-level variation.

Conclusions:

• Cathepsin expression and maturation are influenced by vaginal microbiome composition, suggesting microbiome-mediated regulation of post-translational processing.
• Cathepsin activity appears to be regulated individually, rather than being solely determined by BV diagnosis or CST.
• These findings connect vaginal microbiome dynamics to ECM remodeling and highlight potential links to adverse reproductive outcomes.