Mutations are an important origin of antibiotic resistance in bacteria. While there is increasing evidence showing promoted resistance mutations by environmental stresses, no retrospective research has yet been conducted on this phenomenon and its mechanisms. Herein, we summarized the phenomena of stress-elevated resistance mutations in bacteria, generalized the regulatory mechanisms and discussed the environmental and human health implications. It is shown that both chemical pollutants, such as antibiotics and other pharmaceuticals, biocides, metals, nanoparticles and disinfection byproducts, and non-chemical stressors, such as ultraviolet radiation, electrical stimulation and starvation, are capable of elevating resistance mutations in bacteria. Notably, resistance mutations are more likely to occur under sublethal or subinhibitory levels of these stresses, suggesting a considerable environmental concern. Further, mechanisms for stress-induced mutations are summarized in several points, namely oxidative stress, SOS response, DNA replication and repair systems, RpoS regulon and biofilm formation, all of which are readily provoked by common environmental stresses. Given bacteria in the environment are confronted with a variety of unfavorable conditions, we propose that the stress-elevated resistance mutations are a universal phenomenon in the environment and represent a nonnegligible risk factor for ecosystems and human health. The present review identifies a need for taking into account the pollutants’ ability to elevate resistance mutations when assessing their environmental and human health risks and highlights the necessity of including resistance mutations as a target to prevent antibiotic resistance evolution.

This study focused on the possible chemo-preventive effects of insect peptide CopA3 on normal human colon cells against the inflammation induced by the toxic environmental pollutant aflatoxin B1 (AFB1). In the study, we used CCD 841 CoN normal human colon cells to investigate the cytotoxic effect induced by AFB1 and elucidated the negative impact of AFB1 exposure on the cell cycle progression. Further, we also carried out the in-vivo experiment, where male BALB/c mice were administrated with AFB1 to induce inflammation associated cancer like phenotype and the dietary effect of CopA3 was evaluated on the early stages of AFB1-induced hepatotoxicity and inflammation in colon tissues. At the initiation stage, CopA3 was given along with water, which significantly decreased the inflammation in the liver and colon of AFB1 exposed mice model. Mice that received CopA3 alone showed enhanced activity of several antioxidant enzymes. In the post treatment stage, the CopA3 dosage remarkably increased the Ki-67 protein expression, indicating the enhancement in cell proliferation event and increased the number of apoptotic cells in colonic crypts, suggesting the capability of CopA3 treatment towards the epithelial cell turnover. Thus, CopA3 treatment shows its potential to inhibit the development of the early stages of AFB1-induced colon inflammation and hepatotoxicity in mice by inhibiting the DNA synthesis of the damaged and inflammatory cell and induced apoptosis for the clearance of damaged cells. Collectively, the results of this study suggest that CopA3 treatment may play a protective role against the mycotoxin induced inflammation.

The Pearl River Estuary (PRE) is the largest estuary in southern China and under high metal stress. In the present study, we employed an integrated method of transcriptomics and proteomics to investigate the ecotoxicological effects of trace metals on the Hong Kong oyster Crassostrea hongkongensis. Three oyster populations with distinct spatial distributions of metals were sampled, including the Control (Station QA, the lowest metal levels), the High Cd (Station JZ, the highest Cd), and the High Zn–Cu–Cr–Ni (Station LFS, with the highest levels of zinc, copper, chromium, and nickel). Dominant metals in oysters were differentiated by principal component analysis (PCA), and theirgene and protein profiles were studied using RNA-seq and iTRAQ techniques. Of the 2250 proteins identified at both protein and RNA levels, 70 proteins exhibited differential expressions in response to metal stress in oysters from the two contaminated stations. There were 8 proteins altered at both stations, with the potential effects on mitochondria and endoplasmic reticulum by Ag. The genotoxicity, including impaired DNA replication and transcription, was specifically observed in the High Cd oysters with the dominating influence of Cd. The structural components (cytoskeleton and chromosome-associated proteins) were impaired by the over-accumulated Cu, Zn, Cr, and Ni at Station LFS. However, enhanced tRNA biogenesis and exosome activity might help the oysters to alleviate the toxicities resulting from their exposure to these metals. Our study provided comprehensive information on the molecular changes in oysters at both protein and RNA levels in responding to multi-levels of trace metal stress.

Concerns about the environmental and human health implications of TiO₂ nanoparticles (nTiO₂) are growing with their increased use in consumer and industrial products. Investigations of the underlying molecular mechanisms of nTiO₂ tolerance in organisms will assist in countering nTiO₂ toxicity. In this study, the countermeasures exhibited by the slime mold Physarum polycephalum macroplasmodium against nTiO₂ toxicity were investigated from a physiological, transcriptional, and metabolic perspective. The results suggested that the countermeasures against nTiO₂ exposure include gene-associated metabolic rearrangements in cellular pathways involved in amino acid, carbohydrate, and nucleic acid metabolism. Gene-associated nonmetabolic rearrangements involve processes such as DNA repair, DNA replication, and the cell cycle, and occur mainly when macroplasmodia are exposed to inhibitory doses of nTiO₂. Interestingly, the growth of macroplasmodia and mammal cells was significantly restored by supplementation with a combination of responsive metabolites identified by metabolome analysis. Taken together, we report a novel model organism for the study of nTiO₂ tolerance and provide insights into countermeasures taken by macroplasmodia in response to nTiO₂ toxicity. Furthermore, we also present an approach to mitigate the effects of nTiO₂ toxicity in cells by metabolic intervention.

Fipronil, a phenyl-pyrazole insecticide, has a wide range of uses, from agriculture to veterinary medicine. Due to its large-scale applications, the risk of environmental and occupational exposure and bioaccumulation raises concerns. Moreover, relatively little is known about the intracellular mechanisms of fipronil in trophoblasts and the endometrium involved in implantation. Here, we demonstrated that fipronil reduced the viability of porcine trophectoderm and luminal epithelial cells. Fipronil induced cell cycle arrest at the sub-G1 phase and apoptotic cell death through DNA fragmentation and inhibition of DNA replication. These reactions were accompanied by homeostatic changes, including mitochondrial depolarization and cytosolic calcium depletion. In addition, we found that exposure to fipronil compromised the migration and implantation ability of pTr and pLE cells. Moreover, alterations in PI3K-AKT and MAPK-ERK1/2 signal transduction were observed in fipronil-treated pTr and pLE cells. Finally, the antiproliferative and apoptotic effects of fipronil were also demonstrated in 3D cell culture conditions. In summary, our results suggest that fipronil impairs implantation potentials in fetal trophectoderm and maternal endometrial cells during early pregnancy.

People living a subsistence lifestyle in the Arctic are highly exposed to persistent organic pollutants, including polychlorinated biphenyls (PCBs). Formerly Used Defense (FUD) sites are point sources of PCB pollution; the Arctic contains thousands of FUD sites, many co-located with indigenous villages. We investigated PCB profiles and biological effects in freshwater fish (Alaska blackfish [Dallia pectoralis] and ninespine stickleback [Pungitius pungitius]) living upstream and downstream of the Northeast Cape FUD site on St. Lawrence Island in the Bering Sea. Despite extensive site remediation, fish remained contaminated with PCBs. Vitellogenin concentrations in males indicated exposure to estrogenic contaminants, and some fish were hypothyroid. Downstream fish showed altered DNA methylation in gonads and altered gene expression related to DNA replication, response to DNA damage, and cell signaling. This study demonstrates that, even after site remediation, contaminants from Cold War FUD sites in remote regions of the Arctic remain a potential health threat to local residents – in this case, Yupik people who had no influence over site selection and use by the United States military.

Silver nanoparticles (AgNPs) are widely used because of their excellent antibacterial properties. They are, however, easily discharged into the water environment, causing potential adverse environmental effects. Meta-transcriptomic analyses are helpful to study the transcriptional response of prokaryotic and eukaryotic aquatic microorganisms to AgNPs. In the present study, microcosms were used to investigate the toxicity of AgNPs to a natural aquatic microbial community. It was found that a 7-day exposure to 10 μg L⁻¹ silver nanoparticles (AgNPs) dramatically affected the structure of the microbial community. Aquatic micro eukaryota (including eukaryotic algae, fungi, and zooplankton) and bacteria (i.e., heterotrophic bacteria and cyanobacteria) responded differently to the AgNPs stress. Meta-transcriptomic analyses demonstrated that eukaryota could use multiple cellular strategies to cope with AgNPs stress, such as enhancing nitrogen and sulfur metabolism, over-expressing genes related to translation, amino acids biosynthesis, and promoting bacterial-eukaryotic algae interactions. By contrast, bacteria were negatively affected by AgNPs with less signs of detoxification than in case of eukaryota; various pathways related to energy metabolism, DNA replication and genetic repair were seriously inhibited by AgNPs. As a result, eukaryotic algae (mainly Chlorophyta) dominated over cyanobacteria in the AgNPs treated microcosms over the 7-d exposure. The present study helps to understand the effects of AgNPs on aquatic microorganisms and provides insights into the contrasting AgNPs toxicity in eukaryota and bacteria.

In our earlier work, Tigriopus japonicus were subjected to different mercuric chloride treatments (0–50 μg/L in the seawater) for five generations (F0–F4), and they were subsequently resumed under clean environments for one generation, i.e., F5. Accumulative effects were hypothesized to participate in mercury (Hg) multigenerational toxicity, however phenotypic plasticity could be responsible for metal resistance in this copepod against the long term exposure. Here, we specifically investigated the proteome profiles in the F0, F2, and F5 copepods of the control and 50 μg/L metal treatment, respectively, so as to elucidate the action mechanisms for Hg toxicity/tolerance in T. japonicus under the long term exposure. Functional enrichment analysis showed that a quite different proteomic response was observed in F5 compared with F0 and F2. Namely, the vast majority of enrichments were correlated with the down-regulated proteins in F0 and F2, whereas the enrichments for F5 were mostly attributable to the up-regulated proteins, suggesting that different mechanisms are responsible for Hg toxicity and tolerance (i.e., phenotypic plasticity). Hg toxicity prohibited many proteins in F0 and F2 which are related to several critical processes/pathways, e.g., protein translation, macromolecule metabolic process, DNA replication, cell cycle, cuticle organization, vitellogenesis, etc. In F5, many up-regulated proteins were enriched into compensatory systems, such as carbohydrate metabolism, myosin reorganizations, and stress-related defense pathway. Notably, glycolysis (an oxygen-independent pathway) was enhanced for energy allocation into metal detoxification and tolerance. Taken together, proteomics provides novel mechanistic insights into phenotypic plasticity used by T. japonicus when challenged with cumulative effects due to Hg multigenerational toxicity.

Microorganisms are essential for modifying arsenic morphology, mobility, and toxicity. Still, knowledge of the microorganisms responsible for arsenic metabolism in specific arsenic-contaminated fields, such as metallurgical plants is limited. We sampled on-field soils from three depths at 70 day intervals to explore the distribution and transformation of arsenic in the soil. Arsenic-metabolizing microorganisms were identified from the mapped gene sequences. Arsenic metabolism pathways were constructed with metagenomics and AsChip analysis (a high-throughput qPCR chip for arsenic metabolism genes). It has been shown in the result that 350 genera of arsenic-metabolizing microorganisms carrying 17 arsenic metabolism genes in field soils were identified, as relevant to arsenic reduction, arsenic methylation, arsenic respiration, and arsenic oxidation, respectively. Arsenic reduction genes were the only genes shared by the 10 high-ranking arsenic-metabolizing microorganisms. Arsenic reduction genes (arsABCDRT and acr3) accounted for 73.47%–78.11% of all arsenic metabolism genes. Such genes dominated arsenic metabolism, mediating the reduction of 14.11%–19.86% of As(V) to As(III) in 0–100 cm soils. Arsenic reduction disrupts microbial energy metabolism, DNA replication and repair and membrane transport. Arsenic reduction led to a significant decrease in the abundance of 17 arsenic metabolism genes (p < 0.0001). The critical role of arsenic-reducing microorganisms in the migration and transformation of arsenic in metallurgical field soils, was emphasized with such results. These results were of pronounced significance for understanding the transformation behavior of arsenic and the precise regulation of arsenic in field soil.

Zeolite-supported nanoscale zero-valent iron (Z-NZVI) has great potential for metal(loid) removal, but its encapsulation mechanisms and ecological risks in real soil systems are not completely clear. We conducted long-term incubation experiments to gain new insights into the interactions between metal(loid)s (Cd, Pb, As) and Z-NZVI in naturally contaminated farmland soils, as well as the alteration of indigenous bacterial communities during soil remediation. With the pH-adjusting and adsorption capacities, 30 g kg⁻¹ Z-NZVI amendment significantly decreased the available metal(loid) concentrations by 10.2–96.8% and transformed them into strongly-bound fractions in acidic and alkaline soils after 180 d. An innovative magnetic separation of Z-NZVI from soils followed by XRD and XPS characterizations revealed that B-type ternary complexation, heterogeneous coprecipitation, and/or concurrent redox reactions of metal(loid)s, especially the formation of Cd₃(AsO₄)₂, PbFe₂(AsO₄)₂(OH)₂, and As⁰, occurred only under specific soil conditions. Sequencing of 16S rDNA using Illumina MiSeq platform indicated that temporary shifts in iron-resistant/sensitive, pH-sensitive, denitrifying, and metal-resistant bacteria after Z-NZVI addition were ultimately eliminated because soil characteristics drove the re-establishment of indigenous bacterial community. Meanwhile, Z-NZVI recovered the basic activities of bacterial DNA replication and denitrification functions in soils. These results confirm that Z-NZVI is promising for the long-term remediation of metal(loid)s contaminated farmland soil without significant ecotoxicity.