Mixed heavy metal stress induces global iron starvation response

Abstract

Multiple heavy metal contamination is an increasingly common global problem. Heavy metals have the potential to disrupt microbially mediated biogeochemical cycling. However, systems-level studies on the effects of combinations of heavy metals on bacteria are lacking. For this study, we focused on the Oak Ridge Reservation (ORR; Oak Ridge, TN, USA) subsurface which is contaminated with several heavy metals and high concentrations of nitrate. Using a native Bacillus cereus isolate that represents a dominant species at this site, we assessed the combined impact of eight metal contaminants, all at site-relevant concentrations, on cell processes through an integrated multi-omics approach that included discovery proteomics, targeted metabolomics, and targeted gene-expression profiling. The combination of eight metals impacted cell physiology in a manner that could not have been predicted from summing phenotypic responses to the individual metals. Exposure to the metal mixture elicited a global iron starvation response not observed during individual metal exposures. This disruption of iron homeostasis resulted in decreased activity of the iron-cofactor-containing nitrate and nitrite reductases, both of which are important in biological nitrate removal at the site. We propose that the combinatorial effects of simultaneous exposure to multiple heavy metals is an underappreciated yet significant form of cell stress in the environment with the potential to disrupt global nutrient cycles and to impede bioremediation efforts at mixed waste sites. Our work underscores the need to shift from single- to multi-metal studies for assessing and predicting the impacts of complex contaminants on microbial systems.

Mixed Waste Contamination Selects for a Mobile Genetic Element Population Enriched in Multiple Heavy Metal Resistance Genes

“…AcrAB is a multidrug efflux protein with broad specify that has been implicated in the transport of other compounds related to metal homeostasis such as siderophores 64 . Previously, we found that iron homeostasis is significantly dysregulated in the multi-metal contaminated environments like the ORR subsurface 65 . In contrast, ampC (resistance to penams and cephalosporins) and sunT (resistance to lantibiotics) are enriched in MGEs from low [U] samples.…”

Wildfire Ashes from the Wildland-Urban Interface Alter Vibrio vulnificus Growth and Gene Expression

“…vulnificus, the experimental exposure conditions reflected a slight decrease in concentrations over time, which can be attributed to bacterial metal uptake or metal sorption to other particulates, or a combination of both mechanisms (Figure S3). Bacterial exposure to heavy metals can modulate their growth, physiology, cellular viability, and even biofilm formation. , A recent study has shown that simultaneous exposure to multiple heavy metals can result in a lower bacterial growth rate and growth yield as compared to individual metal exposures and result in a stress response different from the individual metal responses . Studies examining the impacts of mixed metal exposure on Vibrio are limited, but studies where Vibrio isolates have been exposed to individual metals showed tolerance to Cr (0.4−3.2 g L −1 ), Cu (0.5−3.2 g L −1 ), and other heavy metals. − A previous study where Vibrio fischeri was exposed to Zn, Cu, and Cd showed that mixed metal exposures could have synergistic or antagonistic effects on the growth depending on the combined metals …”

“…Bacterial exposure to heavy metals can modulate their growth, physiology, cellular viability, and even biofilm formation. , A recent study has shown that simultaneous exposure to multiple heavy metals can result in a lower bacterial growth rate and growth yield as compared to individual metal exposures and result in a stress response different from the individual metal responses . Studies examining the impacts of mixed metal exposure on Vibrio are limited, but studies where Vibrio isolates have been exposed to individual metals showed tolerance to Cr (0.4−3.2 g L −1 ), Cu (0.5−3.2 g L −1 ), and other heavy metals. − A previous study where Vibrio fischeri was exposed to Zn, Cu, and Cd showed that mixed metal exposures could have synergistic or antagonistic effects on the growth depending on the combined metals …”

Genomic and environmental controls onCastellaniellabiogeography in an anthropogenically disturbed subsurface

“…S3) . Recently, we found that mixed metal exposure may significantly disrupt intracellular iron homeostasis, potentially increasing Fe demand in organisms at sites like the ORR (Goff et al ., 2023). We observed negligible correlations between [Cu], [Cd], [U], [nitrate], and pH and the relative planktonic abundances of the two ASVs in the groundwater.…”

“…There is emerging evidence to suggest that metals in combination interact synergistically or in an antagonistic manner within bacterial systems (Goff et al ., 2023, Pormohammad et al ., 2023). As the ORR subsurface is contaminated by complex and heterogenous mixtures of metals, we focused on microbial resistance to the metal composition present in the FW104 well (Table S1), as FW104 has the highest recorded Castellaniella relative abundance of all ORR sampling sites (Fig.…”