Abstract
BackgroundThe protean chemical properties of mercury have long made it attractive for diverse applications, but its toxicity requires great care in its use, disposal, and recycling. Mercury occurs in multiple chemical forms, and the molecular basis for the distinct toxicity of its various forms is only partly understood. Global transcriptomics applied over time can reveal how a cell recognizes a toxicant and what cellular subsystems it marshals to repair and recover from the damage. The longitudinal effects on the transcriptome of exponential phase E. coli were compared during sub-acute exposure to mercuric chloride (HgCl2) or to phenylmercuric acetate (PMA) using RNA-Seq.ResultsDifferential gene expression revealed common and distinct responses to the mercurials throughout recovery. Cultures exhibited growth stasis immediately after each mercurial exposure but returned to normal growth more quickly after PMA exposure than after HgCl2 exposure. Correspondingly, PMA rapidly elicited up-regulation of a large number of genes which continued for 30 min, whereas fewer genes were up-regulated early after HgCl2 exposure only some of which overlapped with PMA up-regulated genes. By 60 min gene expression in PMA-exposed cells was almost indistinguishable from unexposed cells, but HgCl2 exposed cells still had many differentially expressed genes. Relative expression of energy production and most metabolite uptake pathways declined with both compounds, but nearly all stress response systems were up-regulated by one or the other mercurial during recovery.ConclusionsSub-acute exposure influenced expression of ~45% of all genes with many distinct responses for each compound, reflecting differential biochemical damage by each mercurial and the corresponding resources available for repair. This study is the first global, high-resolution view of the transcriptional responses to any common toxicant in a prokaryotic model system from exposure to recovery of active growth. The responses provoked by these two mercurials in this model bacterium also provide insights about how higher organisms may respond to these ubiquitous metal toxicants.
Highlights
The protean chemical properties of mercury have long made it attractive for diverse applications, but its toxicity requires great care in its use, disposal, and recycling
Bound Hg in cells exposed either to Mercuric chloride (HgCl2) or to phenylmercuric acetate (PMA) declined from ~50% of total Hg added to culture at 10 min to ~20% at 30 min, after which Hg loss from PMA-exposed cells continued to decline to 11% of input at 60 min
We have no simple explanation for this unexpected difference in cell-bound Hg in late exponential phase cultures, it does echo our finding that cultures acutely exposed to 40 μM or 80 μM PMA or HgCl2 bound 24% or 208% more Hg(II) than PhHg, respectively [23]
Summary
The protean chemical properties of mercury have long made it attractive for diverse applications, but its toxicity requires great care in its use, disposal, and recycling. Mercury occurs in multiple chemical forms, and the molecular basis for the distinct toxicity of its various forms is only partly understood. The longitudinal effects on the transcriptome of exponential phase E. coli were compared during sub-acute exposure to mercuric chloride (HgCl2) or to phenylmercuric acetate (PMA) using RNA-Seq. The common metallic element mercury (Hg) has no beneficial biological function and its chemical similarities to essential transition metals such as zinc, copper, and iron make it highly toxic to all living systems. Global mercury emissions range from 6500 to 8500 Mg annually with estimates of half [1, 2] and even two-thirds [3] being anthropogenic and the rest from volcanism. Mercury occurs naturally as the insoluble HgS ore (cinnabar), as inorganic complexes of Hg+2, Hg+1, or (Hg2)2+ of varying solubility depending on available ligands, and as organomercurials generated by microbial and anthropogenic processes. Organomercurials, like phenylmercury, methylmercury, and merthiolate (ethylmercury) have historically been used in medical, industrial and agricultural
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