Mobilome-driven segregation of the resistome in biological wastewater treatment

Abstract

Biological wastewater treatment plants (BWWTP) are considered to be hotspots for the evolution and subsequent spread of antimicrobial resistance (AMR). Mobile genetic elements (MGEs) promote the mobilization and dissemination of antimicrobial resistance genes (ARGs) and are thereby critical mediators of AMR within the BWWTP microbial community. At present, it is unclear whether specific AMR categories are differentially disseminated via bacteriophages (phages) or plasmids. To understand the segregation of AMR in relation to MGEs, we analyzed meta-omic (metagenomic, metatranscriptomic and metaproteomic) data systematically collected over 1.5 years from a BWWTP. Our results showed a core group of 15 AMR categories which were found across all timepoints. Some of these AMR categories were disseminated exclusively (bacitracin) or primarily (aminoglycoside, MLS and sulfonamide) via plasmids or phages (fosfomycin and peptide), whereas others were disseminated equally by both. Combined and timepoint-specific analyses of gene, transcript and protein abundances further demonstrated that aminoglycoside, bacitracin and sulfonamide resistance genes were expressed more by plasmids, in contrast to fosfomycin and peptide AMR expression by phages, thereby validating our genomic findings. In the analyzed communities, the dominant taxon Candidatus Microthrix parvicella was a major contributor to several AMR categories whereby its plasmids primarily mediated aminoglycoside resistance. Importantly, we also found AMR associated with ESKAPEE pathogens within the BWWTP, and here MGEs also contributed differentially to the dissemination of the corresponding ARGs. Collectively our findings pave the way toward understanding the segmentation of AMR within MGEs, thereby shedding new light on resistome populations and their mediators, essential elements that are of immediate relevance to human health.

Reservoirs of antimicrobial resistance in the context of One Health

“…Furthermore, sewage from both the hospital and the general population is ultimately transported to wastewater treatment plants that therefore provide a vast reservoir for AMR [44] . Importantly, the transmission of ARGs via MGEs was further highlighted recently by de Nies et al who reported the segregation of ARG categories between plasmids and phages in wastewater treatment plants [45] . Recent evidence suggests that anthropogenic forcing of environments has led to increased AMR in the environment, such as Antarctica, that was previously recognized as pristine [46] .…”

Insight into antimicrobial resistance at a new beef cattle feedlot in western Canada

“…Thus, while the presence of floR (a phenicol exporter) and estT (a macrolide esterase) can be rationalized by the use of both classes of antibiotics during the study period, the current global status of the mobile resistome should not be ignored. ARGs are found throughout the biosphere with water systems, in particular, biological wastewater treatment facilities impacting their patterns of dissemination in mobile genetic elements of bacteria ( 24 ).…”

Genome-centric analyses of 165 metagenomes show that mobile genetic elements are crucial for the transmission of antimicrobial resistance genes to pathogens in activated sludge and wastewater

“…6A ), suggesting that these ARGs were transmitted through VGT (inheritance from parent to offspring). A study identified a mobile resistome in WW, where most of the ARGs were associated with chromosomes ( 35 ), and only small proportions (10.8%) were found on plasmids, highlighting the involvement of other genetic elements in the spread of ARGs. Shi et al revealed the potential of VGT through the proliferation of ARG hosts and showed that more ARGs are located on chromosomes than on plasmids ( 58 ).…”

“…MAGs may help identify MGEs in hosts, such as plasmids. Identification of plasmids in a given host can be challenging because plasmids are self-replicating ( 35 ) and can be hosted by more than one species ( 34 , 36 ). Notably, plasmids are known to be significant vectors for gene transfer in many bacterial populations than any other mobile genetic elements ( 34 , 37 ).…”