Impact of Heavy Metal and Resistance Genes on Antimicrobial Resistance: Ecological and Public Health Implications

Abstract

Heavy metals (HMs) are widespread pollutants that can exert selection pressure on microbial populations due to their toxicity and persistence, leading to the evolution of heavy metal resistance genes (HMRGs). These genes are part of the resistome, and their spread often occurs via mobile genetic elements that allow co-selection with antibiotic and biocide resistance genes. Such processes have an impact on microbial biodiversity, biogeochemical cycling and public health in agriculture, industry and urban areas. The selection pressure exerted by HM promotes the spread of multidrug-resistant strains and thus increases ecological and health risks. This review discusses the interaction between HMRGs and genetic determinants such as virulence genes that influence biofilm formation, cellular homeostasis and oxidative stress. It also discusses the dual role of HMRGs in promoting ecological functions such as bioremediation while potentially limiting them by reducing microbial diversity. Understanding such interactions contributes significantly to targeting different systems to overcome the challenges associated with antimicrobial resistance (AMR).

Keywords: co-selection of resistance; heavy metal resistance; heavy metal resistome.

Figure 1

Heavy metals resistance systems for prokaryotes and eukaryotes. (A) The resistance systems to As, Cr, Pb and Hg correspond to both Gram-negative and Gram-positive organisms and reside in the ars, chr, pbr and mer operons, respectively, while the system for Cu includes the cue, cus, pco and cop operons. The resistance systems exclusively for Gram-negative bacteria to Zn include the znu and zur operons, in addition to the ZnT proteins and the czc system, which is shared with Co and Cd. (B) For Gram-positive bacteria, the systems for Cu and Cd exclusively include homologs of cop and the cad operon, respectively. (C) Eukaryotic systems include fungal membrane proteins resistant to As, Cr, Pb, Cd and Zn and vacuolar transporters for Cd, Zn and As, as well as reactive compounds in the cytoplasm and functional groups in the cell wall of fungi and microalgae that react with HMs. Figure created from BioRender.

Figure 2

Development and dissemination of HMRGs in natural and anthropogenic environments, influenced by the environmental chemical speciation of the HMs and by the presence of other sources of pollution (wastewater, solid waste, atmospheric emissions from combustion or energy consumption and agrochemicals). Three main factors are recognized: a human factor, which includes human populations and anthropogenic environments such as agricultural, industrial areas and clinical centers; an animal factor, which includes wild and farmed organisms and an environmental factor, made up of natural resources and microbial reservoirs, such as human and animal microbiota, and the microbiomes of soil and water bodies. It is in these reservoirs where HMRGs mainly reside and where AMR is promoted. Figure created from WPS Slides.