The global rise and spread of antibiotic resistance greatly challenge the treatment of bacterial infections. Wastewater treatment plants (WWTPs) harbor and discharge antibiotic resistance genes (ARGs) as environmental contaminants. However, the knowledge gap on the host identity, activity, and functionality of ARGs limits transmission and health risk assessment of the WWTP resistome. Hereby, a genome-centric quantitative metatranscriptomic approach was exploited to realize high-resolution qualitative and quantitative analyses of bacterial hosts of ARGs (i.e., multiresistance, pathogenicity, activity, and niches) in the 12 urban WWTPs. We found that ∼45% of 248 recovered genomes expressed ARGs against multiple classes of antibiotics, among which bacitracin and aminoglycoside resistance genes in Proteobacteria were the most prevalent scenario. Both potential pathogens and indigenous denitrifying bacteria were transcriptionally active hosts of ARGs. The almost unchanged relative expression levels of ARGs in the most resistant populations (66.9%) and the surviving ARG hosts including globally emerging pathogens (e.g., Aliarcobacter cryaerophilus) in treated WWTP effluent prioritize future examination on the health risks related to resistance propagation and human exposure in the receiving environment.

The antibiotic resistance crisis underlies globally increasing failures in treating deadly bacterial infections, largely due to the selection of antibiotic resistance genes (ARG) collection, known as the resistome, in human gut microbiota. So far, little is known about the relationship between gut antibiotic resistome and host metabolic disorders such as type 2 diabetes (T2D). Here, metagenomic landscape of gut antibiotic resistome is profiled in a large multiomics human cohort (n = 1210). There is a significant overall shift in gut antibiotic resistome structure among healthy, prediabetes, and T2D groups. It is found that larger ARG diversity is associated with a higher risk of T2D. The novel diabetes ARG score is positively associated with glycemic traits. Longitudinal validation analysis confirms that the ARG score is associated with T2D progression, characterized by the change of insulin resistance. Collectively, the data describe the profiles of gut antibiotic resistome and support its close relationship with T2D progression.

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Viruses influence biogeochemical cycles in oceans, freshwater, soil, and human gut through infection and by modulating virocell metabolism through virus-encoded auxiliary metabolic genes (vAMGs). However, the geographical distribution, potential metabolic function, and engineering significance of vAMGs in wastewater treatment plants (WWTPs) remain to be explored. Here, 752 single-contig viral genomes with high confidence, 510 of which belonged to Caudovirales, were recovered from the activated sludge metagenomes of 32 geographically distributed WWTPs. A total of 101 vAMGs involved in various metabolic pathways were identified, the most common of which were the queuosine biosynthesis genes folE, queD, and queE and the sulfur metabolism gene cysH. Phylogenetic analysis and virus–host relationship prediction revealed the probable evolutionary histories of vAMGs involved in carbon (acpP and prsA), nitrogen (amoC), sulfur (cysH), and phosphate (phoH) metabolism, which potentially mediate microbial carbon and nutrient cycling. Notably, 11 of the 38 (28.3%) vAMGs identified in the metagenomes with corresponding metatranscriptomes were transcriptionally expressed, implying an active functional state. This meta-analysis provides the first broad catalog of vAMGs in municipal WWTPs and how they may assist in the basic physiological reactions of their microbial hosts or nutrient cycling in the WWTPs, and therefore, may have important effects on the engineering of wastewater treatment processes.