Zinc Exposure Promotes Commensal-to-Pathogen Transition in <i>Pseudomonas aeruginosa</i> Leading to Mucosal Inflammation and Illness in Mice
The opportunistic pathogen <i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>) is associated gastrointestinal (GI) inflammation and illness; however, factors motivating commensal-to-pathogen transition are unclear. Excessive zinc intake from supplements is common in humans....
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/24/13321 |
| Summary: | The opportunistic pathogen <i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>) is associated gastrointestinal (GI) inflammation and illness; however, factors motivating commensal-to-pathogen transition are unclear. Excessive zinc intake from supplements is common in humans. Due to the fact that zinc exposure enhances <i>P. aeruginosa</i> colonization in vitro, we hypothesized zinc exposure broadly activates virulence mechanisms, leading to inflammation and illness. <i>P. aeruginosa</i> was treated with excess zinc and growth, expression and secretion of key virulence factors, and biofilm production were determined. Effects on invasion, barrier function, and cytotoxicity were evaluated in Caco-2 cells co-cultured with <i>P. aeruginosa</i> pre-treated with zinc. Effects on colonization, mucosal pathology, inflammation, and illness were evaluated in mice infected with <i>P. aeruginosa</i> pre-treated with zinc. We found the expression and secretion of key virulence factors involved in quorum sensing (QS), motility (type IV pili, flagella), biosurfactants (rhamnolipids), toxins (exotoxin A), zinc homeostasis (CzcR), and biofilm production, were all significantly increased. Zinc exposure significantly increased <i>P. aeruginosa</i> invasion, permeability and cytotoxicity in Caco-2 cells, and enhanced colonization, inflammation, mucosal damage, and illness in mice. Excess zinc exposure has broad effects on key virulence mechanisms promoting commensal-to-pathogen transition of <i>P. aeruginosa</i> and illness in mice, suggesting excess zinc intake may have adverse effects on GI health in humans. |
|---|---|
| ISSN: | 1661-6596 1422-0067 |