Cross-Kingdom Comparative Transcriptomics Reveals Conserved Genetic Modules in Response to Cadmium Stress

It is known that organisms have developed various mechanisms to cope with cadmium (Cd) stress, while we still lack a system-level understanding of the functional isomorphy among them. In the present study, a cross-kingdom comparison was conducted among Escherichia coli, Saccharomyces cerevisiae, and Chlamydomonas reinhardtii, through toxicological tests, comparative transcriptomics, as well as conventional functional genomics. An equivalent level of Cd stress was determined via inhibition tests. Through transcriptome comparison, the three organisms exhibited differential gene expression under the same Cd stress relative to the corresponding no-treatment control. Results from functional enrichment analysis of differentially expressed genes (DEGs) showed that four metabolic pathways responsible for combating Cd stress were commonly regulated in the three organisms, including antioxidant reactions, sulfur metabolism, cell wall remodeling, and metal transport. In vivo expression patterns of 43 DEGs from the four pathways were further examined using quantitative PCR and resulted in a relatively comparable dynamic of gene expression patterns with transcriptome sequencing (RNA-seq). Cross-kingdom comparison of typical Cd stress-responding proteins resulted in the detection of 12 groups of homologous proteins in the three species. A class of potential metal transporters were subjected to cross-transformation to test their functional complementation. An ABC transporter gene in E. coli, possibly homologous to the yeast ycf1, was heterologously expressed in S. cerevisiae, resulting in enhanced Cd tolerance. Overall, our findings indicated that conserved genetic modules against Cd toxicity were commonly regulated among distantly related microbial species, which will be helpful for utilizing them in modifying microbial traits for bioremediation. IMPORTANCE Research is establishing a systems biology view of biological response to Cd stress. It is meaningful to explore whether there is regulatory isomorphy among distantly related organisms. A transcriptomic comparison was done among model microbes, leading to the identification of a conserved cellular model pinpointing the generic strategies utilized by microbes for combating Cd stress. A novel E. coli transporter gene substantially increased yeast's Cd tolerance. Knowledge on systems understanding of the cellular response to metals provides the basis for developing bioengineering remediation technology.