During the last two decades, the number of difficult-to-treat infections on account of multidrug-resistant and extended spectrum β-lactamase-(ESBL)-producing Enterobacterales has rised to a remarkable degree, which has resulted in an increased usage of the antibiotics carbapenems and colistin (Peyclit et al., 2019). As last-resort antibiotic therapies, carbapenems play a crucial part in the treatment of these infections whereas for carbapenem-resistant Enterobacterales (CRE) infections, colistin is the last-resort antibiotic (Oliveira et al., 2020). Carbapenems and colistin are categorized as critically important drugs and so the emergence of resistance to these antibiotics is a serious public health concern (WHO, 2019). In 2015, in China, a plasmid-mediated colistin resistance gene, mcr-1, was first identified in E. coli isolated from a pig (Liu et al., 2016). Shortly after, the gene was reported among numerous bacterial species in different ecological niches in more than 70 countries on 5 continents (Nang et al., 2019). In China, the widespread dissemination of mcr-1 has been attributed to selective pressure generated by colistin used in animal husbandry, which promotes the spread of mcr-1-carrying plasmids (Shen et al., 2016). Therefore, the use of colistin as a feed additive was banned from May 1, 2017, in China, reducing its annual use by more than 8000 tons (Walsh and Wu, 2016). Nevertheless, misuse and overuse of colistin still occurs.

Colistin- and carbapenem-resistant Escherichia coli (CCREC) co-producing mcr-1 and carbapenem resistance genes (such as blaNDM-genes) have been increasingly reported among isolates from animals, humans, and the environment (Bilal et al., 2021; Feng et al., 2021; Nukui et al., 2019; Wang et al., 2021). Infections caused by such strains are also increasing (Bao et al., 2022; Bilal et al., 2021; Hameed et al., 2021; Lin et al., 2020; Yan et al., 2021). These infections constitute a major therapeutic challenge. As CCREC are often multidrug-resistant besides, no standardized treatment strategies are available.

Wastewater treatment plants (WWTPs) link human activities and the environment and can act as reservoirs and sources from which antibiotic resistance emergence (Guo et al., 2017; Wright, 2019). As WWTPs collect and treat municipal, domestic, hospital, and slaughterhouse wastewater, concentrated populations of microbes from diverse sources coupled with diverse selection pressures exerted from compounds in waste from different origins (e.g., antibiotic pollution from hospital waste) create favorable conditions for the transfer of antibiotic resistance genes (ARGs) and proliferation of antibiotic-resistant bacteria (ARB) (Magiorakos et al., 2012). WWTPs reduce the number of bacteria, but do not eliminate them entirely, so ARGs, ARB, and potential pathogens may disseminate into the environment via the outlet water or sludge, and subsequently contact with bacteria in the environment, poultry and humans (Beattie et al., 2020; Nguyen et al., 2021).

Therefore, it is crucial to monitor WWTPs for the detection of colistin- and carbapenem-resistant Escherichia coli. The objective of this study was to explore the occurrence of CCREC in sewage and sludge samples from seven functional units of a large WWTP in Eastern China, during the different seasons of 2018, and characterize isolates of CCREC in terms of antimicrobial susceptibility, ARGs, virulence genes and sequence type. Additionally, the mobile genetic elements on which the CCREC carry their colistin- and carbapenem resistance genes were also the focus of our study.