Metals are overlooked in the evolution of antibiotic resistance

Abstract

● Metals are increasingly important risk factors for the evolution of antibiotic resistance in environments.

The rapid development of antibiotic resistance is occurring at a global scale. We therefore stride into the post-antibiotic era and have to battle antibiotic resistance in the Anthropocene. Metals are widely used and their pollution is widespread worldwide. More importantly, metal-induced co-selection greatly expands the environmental resistomes and increases the health risk of antibiotic resistance in environments. Here, we reviewed the metal-induced co-selection and their increasingly important roles in the development of antibiotic resistance. In particular, we highlight the metal-rich environments that maintain reservoirs for high-risk antibiotic resistance genes with horizontally transferable potentials. We also call for considerations and further investigations of other co-selective agents and the efficacy of metal-based interventions to better manage and combat the global antibiotic resistance crisis within the One Health framework.

Graphical abstract

Keywords

antibiotic resistance / metals / co-selection / mobile genetic elements / One Health

References

[1] Babakhani, S., Oloomi, M., 2018. Transposons: the agents of antibiotic resistance in bacteria. Journal of Basic Microbiology58, 905–917.

[2] Baker-Austin, C., Wright, M.S., Stepanauskas, R., McArthur, J.V., 2006. Co-selection of antibiotic and metal resistance. Trends in Microbiology14, 176–182.

[3] Berg, J., Tom-Petersen, A., Nybroe, O., 2005. Copper amendment of agricultural soil selects for bacterial antibiotic resistance in the field. Letters in Applied Microbiology40, 146–151.

[4] Cantón, R., Ruiz-Garbajosa, P., 2011. Co-resistance: an opportunity for the bacteria and resistance genes. Current Opinion in Pharmacology11, 477–485.

[5] Ding, J., Zhu, D., Wang, Y., Wang, H.T., Liang, A.P., Sun, H.W., Chen, Q.L., Lassen, S.B., Lv, M., Chen, Q.L., 2021. Exposure to heavy metal and antibiotic enriches antibiotic resistant genes on the tire particles in soil. Science of the Total Environment792, 148417.

[6] Du, D.J., Wang-Kan, X., Neuberger, A., van Veen, H.W., Pos, K.M., Piddock, L.J.V., Luisi, B.F., 2018. Multidrug efflux pumps: structure, function and regulation. Nature Reviews Microbiology16, 523–539.

[7] Frei, A., Verderosa, A.D., Elliott, A.G., Zuegg, J., Blaskovich, M.A.T., 2023. Metals to combat antimicrobial resistance. Nature Reviews Chemistry7, 202–224.

[8] Frost, L.S., Leplae, R., Summers, A.O., Toussaint, A., 2005. Mobile genetic elements: the agents of open source evolution. Nature Reviews Microbiology3, 722–732.

[9] Gillings, M.R., 2014. Integrons: past, present, and future. Microbiology and Molecular Biology Reviews78, 257–277.

[10] Gillings, M.R., Gaze, W.H., Pruden, A., Smalla, K., Tiedje, J.M., Zhu, Y.G., 2015. Using the class 1 integron-integrase gene as a proxy for anthropogenic pollution. The ISME Journal9, 1269–1279.

[11] Gupta, S., Graham, D.W., Sreekrishnan, T.R., Ahammad, S.Z., 2022. Effects of heavy metals pollution on the co-selection of metal and antibiotic resistance in urban rivers in UK and India. Environmental Pollution306, 119326.

[12] Hao, X.L., Zhu, J.J., Rensing, C., Liu, Y., Gao, S.H., Chen, W.L., Huang, Q.Y.; Liu, Y.R., 2021. Recent advances in exploring the heavy metal(loid) resistant microbiome. Computational and Structural Biotechnology Journal19, 94–109.

[13] Kang, W., Zhang, Y.J., Shi, X., He, J.Z., Hu, H.W., 2018. Short-term copper exposure as a selection pressure for antibiotic resistance and metal resistance in an agricultural soil. Environmental Science and Pollution Research25, 29314–29324.

[14] Knapp, C.W., Callan, A.C., Aitken, B., Shearn, R., Koenders, A., Hinwood, A., 2017. Relationship between antibiotic resistance genes and metals in residential soil samples from Western Australia. Environmental Science and Pollution Research24, 2484–2494.

[15] Knapp, C.W., McCluskey, S.M., Singh, B.K., Campbell, C.D., Hudson, G., Graham, D.W., 2011. Antibiotic resistance gene abundances correlate with metal and geochemical conditions in archived Scottish soils. PLoS One6, e27300.

[16] Knöppel, A., Näsvall, J., Andersson, D.I., 2017. Evolution of antibiotic resistance without antibiotic exposure. Antimicrobial Agents and Chemotherapy61, e01495–17.

[17] Kwon, J.H., Powderly, W.G., 2021. The post-antibiotic era is here. Science373, 471–471.

[18] Larsson, D.G.J., Flach, C.F., 2022. Antibiotic resistance in the environment. Nature Reviews Microbiology20, 257–269.

[19] Lemire, J.A., Harrison, J.J., Turner, R.J., 2013. Antimicrobial activity of metals: mechanisms, molecular targets and applications. Nature Reviews Microbiology11, 371–384.

[20] Li, B., Yang, Y., Ma, L.P., Ju, F., Guo, F., Tiedje, J.M., Zhang, T., 2015. Metagenomic and network analysis reveal wide distribution and co-occurrence of environmental antibiotic resistance genes. The ISME Journal9, 2490–2502.

[21] Li, L.G., Xia, Y., Zhang, T., 2017. Co-occurrence of antibiotic and metal resistance genes revealed in complete genome collection. The ISME Journal11, 651–662.

[22] Mahbub, K.R., King, W.L., Siboni, N., Nguyen, V.K., Rahman, M.M., Megharaj, M., Seymour, J.R., Franks, A.E., Labbate, M., 2020. Long-lasting effect of mercury contamination on the soil microbiota and its co-selection of antibiotic resistance. Environmental Pollution265, 115057.

[23] Mazhar, S.H., Li, X.J., Rashid, A., Su, J.M., Xu, J.Q., Brejnrod, A.D., Su, J.Q., Wu, Y.J., Zhu, Y.G., Zhou, S.G., Feng, R.W., Rensing, C., 2021. Co-selection of antibiotic resistance genes, and mobile genetic elements in the presence of heavy metals in poultry farm environments. Science of the Total Environment755, 142702.

[24] Nriagu, J.O., 1996. A history of global metal pollution. Science272, 223–223.

[25] Pal, C., Bengtsson-Palme, J., Kristiansson, E., Larsson, D.G.J., 2015. Co-occurrence of resistance genes to antibiotics, biocides and metals reveals novel insights into their co-selection potential. BMC Genomics16, 964.

[26] Poole, K., 2017. At the nexus of antibiotics and metals: the impact of Cu and Zn on antibiotic activity and resistance. Trends in Microbiology25, 820–832.

[27] Pu, Q., Fan, X.T., Sun, A.Q., Pan, T., Li, H., Bo Lassen, S., An, X.L., Su, J.Q., 2021. Co-effect of cadmium and iron oxide nanoparticles on plasmid-mediated conjugative transfer of antibiotic resistance genes. Environment International152, 106453.

[28] Roberto, A.A., Van Gray, J.B., Engohang-Ndong, J., Leff, L.G., 2019. Distribution and co-occurrence of antibiotic and metal resistance genes in biofilms of an anthropogenically impacted stream. Science of the Total Environment688, 437–449.

[29] Seiler, C., Berendonk, T.U., 2012. Heavy metal driven co-selection of antibiotic resistance in soil and water bodies impacted by agriculture and aquaculture. Frontiers in Microbiology3, 399.

[30] Shi, L.D., Xu, Q.J., Liu, J.Y., Han, Z.X., Zhu, Y.G., Zhao, H.P., 2021. Will a non-antibiotic metalloid enhance the spread of antibiotic resistance genes: the selenate story. Environmental Science & Technology55, 1004–1014.

[31] Song, J.X., Rensing, C., Holm, P.E., Virta, M., Brandt, K.K., 2017. Comparison of metals and tetracycline as selective agents for development of tetracycline resistant bacterial communities in agricultural soil. Environmental Science & Technology51, 3040–3047.

[32] Stepanauskas, R., Glenn, T.C., Jagoe, C.H., Tuckfield, R.C., Lindell, A.H., King, C.J., McArthur, J.V., 2006. Coselection for microbial resistance to metals and antibiotics in freshwater microcosms. Environmental Microbiology8, 1510–1514.

[33] van Boeckel, T.P., Gandra, S., Ashok, A., Caudron, Q., Grenfell, B.T., Levin, S.A., Laxminarayan, R., 2014. Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. The Lancet Infectious Diseases14, 742–750.

[34] Wang, F.F., Liu, G.P., Zhang, F., Li, Z.M., Yang, X.L., Yang, C.D., Shen, J.L., He, J.Z., Li, B.L., Zeng, J.G., 2022. Natural selenium stress influences the changes of antibiotic resistome in seleniferous forest soils. Environmental Microbiome17, 26.

[35] Wang, X.M., Lan, B.R., Fei, H.X., Wang, S.Y., Zhu, G.B., 2021. Heavy metal could drive co-selection of antibiotic resistance in terrestrial subsurface soils. Journal of Hazardous Materials411, 124848.

[36] WHO, 2015. WHO Model Lists of Essential Medicines [Online]. available at the WHO website.

[37] Yazdankhah, S., Rudi, K., Bernhoft, A., 2014. Zinc and copper in animal feed - development of resistance and co-resistance to antimicrobial agents in bacteria of animal origin. Microbial Ecology in Health and Disease 25.

[38] Zhang, Z.Y., Zhang, Q., Wang, T.Z., Xu, N.H., Lu, T., Hong, W.J., Penuelas, J., Gillings, M., Wang, M.X., Gao, W.W., Qian, H.F., 2022. Assessment of global health risk of antibiotic resistance genes. Nature Communications13, 1553.

[39] Zhao, Y., Cocerva, T., Cox, S., Tardif, S., Su, J.Q., Zhu, Y.G., Brandt, K.K., 2019. Evidence for co-selection of antibiotic resistance genes and mobile genetic elements in metal polluted urban soils. Science of the Total Environment656, 512–520.

[40] Zhao, Y., Hu, H.W., Su, J.Q., Hao, X.L., Guo, H.M., Liu, Y.R., Zhu, Y.G., 2021. Influence of legacy mercury on antibiotic resistomes: evidence from agricultural soils with different cropping systems. Environmental Science & Technology55, 13913–13922.

[41] Zhao, Y., Su, J.Q., An, X.L., Huang, F.Y., Rensing, C., Brandt, K.K., Zhu, Y.G., 2018. Feed additives shift gut microbiota and enrich antibiotic resistance in swine gut. Science of the Total Environment621, 1224–1232.

[42] Zhou, B.R., Wang, C., Zhao, Q., Wang, Y., Huo, M.J., Wang, J.D., Wang, S.L., 2016. Prevalence and dissemination of antibiotic resistance genes and coselection of heavy metals in Chinese dairy farms. Journal of Hazardous Materials320, 10–17.

[43] Zhu, Y.G., Johnson, T.A., Su, J.Q., Qiao, M., Guo, G.X., Stedtfeld, R.D., Hashsham, S.A., Tiedje, J.M., 2013. Diverse and abundant antibiotic resistance genes in Chinese swine farms. Proceedings of the National Academy of Sciences of the United States of America110, 3435–3440.

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