Plasmid Genomes Reveal the Distribution, Abundance, and Organization of Mercury-Related Genes and Their Co-Distribution with Antibiotic Resistant Genes in Gammaproteobacteria

Abstract

Mercury (Hg) pollution poses human health and environmental risks worldwide, as it can have toxic effects and causes selective pressure that facilitates the spread of antibiotic resistant genes (ARGs) among microbes. More and more studies have revealed that numerous Hg-related genes (HRGs) can help to resist and transform Hg. In the present study, we systematically analyzed the HRG distribution, abundance, organization, and their co-distribution with ARGs, using 18,731 publicly available plasmid genomes isolated from a Gammaproteobacteria host. Our results revealed that there were many Hg-resistant (mer) operon genes but they were not extensively distributed across plasmids, with only 9.20% of plasmids harboring HRGs. Additionally, no hgcAB genes (which methylate Hg to create methylmercury) were identified in any of the analyzed plasmids. The host source significantly influenced the number of HRGs harbored by plasmids; plasmids isolated from humans and animals harbored a significantly smaller number of HRGs than plasmids isolated from the wastewater and sludge. HRG clusters displayed an extremely high organizational diversity (88 HRG cluster types), though incidences of more than half of the HRG cluster types was <5. This indicates the frequent rearrangement among HRGs in plasmids. The 1368 plasmids harboring both HRGs and ARGs, were dominated by Klebsiella, followed by Escherichia, Salmonella, and Enterobacter. The tightness of the HRG and ARG co-distribution in plasmids was affected by the host sources but not by pathogenicity. HRGs were more likely to co-occur with specific ARG classes (sulfonamide, macrolide-lincosamide-streptogramin, and aminoglycoside resistance genes). Collectively, our results reveal the distribution characteristics of HRGs in plasmids, and they have important implications for further understanding the environmental risks caused by the spread of ARGs through the plasmid-mediated co-transfer of ARGs and HRGs.