Document Type

Honors Thesis

Major

Biochemistry

Advisor(s)

Julie Gosse

Committee Members

Melissa Maginnis, Christopher Mares, Sally Molloy, Melody Neely

Graduation Year

May 2020

Publication Date

2025

Abstract

Triclosan (TCS) is an antimicrobial agent that was banned by the FDA from hand soaps in 2016, hospital soaps in 2017, and hand sanitizers in 2019; however, TCS can still be found in various products. The Gosse lab previously observed that TCS inhibits mast cell and mitochondrial function. Mast cells are a ubiquitous immune cell type that depend on Ca2+ influx into the cytosol for proper function. The Gosse lab previously showed that TCS depolarizes the mitochondrial membrane, disrupts mitochondrial structure, and inhibits Ca2+ dynamics in mast cells, and here we show that TCS also inhibits Ca2+ in human Jurkat T-cells. However, the molecular mechanism behind the Ca2+ dampening has yet to be elucidated. Inhibition of the plasma membrane electrochemical potential (PMP) can inhibit mast cell function. However, we also show in both mast cells and T-cells, using the genetically encoded voltage indicators (GEVIs) ArcLight (pH sensitive) and ASAP2 (pH insensitive), that TCS does not disrupt PMP, but rather induces acidification of the cytosol, at consumer-relevant, non-cytotoxic, doses. Additionally, this acidification effect was confirmed using a genetically encoded pH-sensitive reporter (pHlourin). Acidification of the cytosol has previously been linked to Ca2+ influx inhibition, thus providing a mechanistic explanation of triclosan’s disruption of Ca2+ influx and, thus, of immune cell function.

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