A multi-domain snail metallothionein increases cadmium resistance and fitness in Caenorhabditis elegans

Abstract

Metallothioneins (MTs) are a family of mostly low-molecular weight, cysteine-rich proteins capable of specific metal-ion binding that are involved in metal detoxification and homeostasis, as well as in stress response. In contrast to most other animal species which possess two-domain (bidominial) MTs, some gastropod species have evolved Cd²⁺-selective multidomain MTs (md-MTs) consisting of several concatenated β3 domains and a single C-terminal β1 domain. Each domain contains three-metal ion clusters and binds three metal ions. The terrestrial snail Alinda biplicata possesses, among other MT isoforms, an md-MT with nine β3 domains and a C-terminal β1 domain (termed 10md-MT), capable of binding up to 30 Cd²⁺ ions per protein molecule. In the present study, the Alinda biplicata 10md-MT gene and a truncated version consisting of one β3 domain and a single C-terminal β1 domain (2d-MT) were introduced into a Caenorhabditis elegans knock-out strain lacking a native MT gene (mtl-1). The two snail MT constructs consistently increased Cd²⁺ resistance, and partially improved morphological, life history and physiological fitness traits in the nematode model host Caenorhabditis elegans. This highlights how the engineering of transgenic Caenorhabditis elegans strains expressing snail MTs provides an enhancement of the innate metal detoxification mechanism and in doing so provides a platform for enhanced mechanistic toxicology.