New perspectives on mobile genetic elements: a paradigm shift for managing the antibiotic resistance crisis

Mobile genetic elements (MGEs) are primary facilitators in the global spread of antibiotic resistance. Here, we present novel ecological and evolutionary perspectives to understand and manage these elements: as selfish entities that exhibit biological individuality, as pollutants that replicate and as invasive species that thrive under human impact. Importantly, each viewpoint suggests new means to control their activity and spread. When seen as biological individuals, MGEs can be regarded as therapeutic targets in their own right. We highlight promising conjugation-inhibiting compounds that could be administered alongside antibiotic treatment. Viewed as pollutants, sewage treatment methods could be modified to efficiently remove antimicrobials and the resistance genes that they select. Finally, by recognizing the invasive characteristics of MGEs, we might apply strategies developed for the management of invasive species. These include environmental restoration to reduce antimicrobial selection, early detection to help inform appropriate antibiotic usage, and biocontrol strategies that target MGEs, constituting precision antimicrobials. These actions, which embody the One Health approach, target different characteristics of MGEs that are pertinent at the cellular, community, landscape and global levels. The strategies could act on multiple fronts and, together, might provide a more fruitful means to combat the global resistance crisis. This article is part of the theme issue ‘The secret lives of microbial mobile genetic elements’.

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Extended spectrum β-lactamase and carbapenemase genes are substantially and sequentially reduced during conveyance and treatment of urban sewage

10.1101/2020.11.12.379032 ◽

2020 ◽

Author(s):

Liguan Li ◽

Joseph Nesme ◽

Marcos Quintela-Baluja ◽

Sabela Balboa ◽

Syed Hashsham ◽

...

Keyword(s):

Antibiotic Resistance ◽

Sewage Treatment ◽

Resistance Management ◽

Antibiotic Resistance Genes ◽

Mobile Genetic Elements ◽

Water Systems ◽

Urban Water ◽

Genetic Elements ◽

Urban Sewage ◽

Extended Spectrum

AbstractIntegrated and quantitative observations of antibiotic resistance genes (ARGs) in urban water systems (UWSs) are lacking. We sampled three UWSs for clinically important extended spectrum β-lactamase (ESBL) and carbapenemase (CP) genes, mobile genetic elements and microbial communities. Sewage – especially from hospitals – carried substantial loads of ESBL and CP genes (106 – 107 per person equivalent), but those loads progressively declined along the UWS, resulting in minimal emissions (101 – 104 copies per person equivalent). Removal was primarily during sewage conveyance (65% ± 36%) rather than within sewage treatment (34% ± 23%). The ARGs clustered in groups based on their persistence; less persistent groups were associated to putative host taxa (especially Enterobacteriaceae and Moraxellaceae), while more persistent groups appear horizontally transferred as they correlated with mobile genetic elements. This first documentation of a substantial ARG reduction during sewage conveyance provides opportunities for antibiotic resistance management and a caution for sewage-based ARG surveillance.

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Biochar and Hyperthermophiles as Additives Accelerate the Removal of Antibiotic Resistance Genes and Mobile Genetic Elements during Composting

Materials ◽

10.3390/ma14185428 ◽

2021 ◽

Vol 14 (18) ◽

pp. 5428

Author(s):

Yanli Fu ◽

Aisheng Zhang ◽

Tengfei Guo ◽

Ying Zhu ◽

Yanqiu Shao

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

High Throughput Sequencing ◽

Sewage Treatment ◽

Antibiotic Resistance Genes ◽

Mobile Genetic Elements ◽

Integrase Gene ◽

Genetic Elements ◽

Real Time Quantitative Pcr ◽

Class 1

Sewage treatment plants are known as repositories of antibiotic resistance genes (ARGs). Adding biochar and inoculating with exogenous microbial agents are common ways to improve the quality of compost. However, little is known about the effects of these exogenous additives on the fate of ARGs during composting and the related mechanisms. In this study, municipal sludge was taken as the research object to study the ARG-removal effects of four composting methods: ordinary compost (CT), compost with hyperthermophiles (HT), compost with hyperthermophiles and 2.0% biochar (HT2C) and compost with hyperthermophiles and 5.0% biochar (HT5C). Real-time quantitative PCR (qPCR) and 16S rRNA high-throughput sequencing were conducted to analyze the ARGs, MGEs and bacterial community. After composting, the abundance of ARGs in CT was reduced by 72.7%, while HT, HT2C and HT5C were reduced by 80.7%, 84.3% and 84.8%, respectively. Treatments with different proportions of biochar added (HT2C, HT5C) had no significant effect on the abundance of ARGs. Network analysis showed that Firmicutes and Nitrospirae were positively associated with most ARGs and may be potential hosts for them. In addition, redundancy analysis further showed that the class 1 integrase gene (intI1), pH and organic carbon had a greater effect on ARGs. Our findings suggested that the combination of hyperthermophiles and biochar during the composting process was an effective way to control ARGs and mobile genetic elements (MGEs), thus inhibiting the spread and diffusion of ARGs in the environment and improving the efficiency of treating human and animal diseases.

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Shotgun metagenomic analysis reveals the prevalence of antibiotic resistance genes and mobile genetic elements in full scale hospital wastewater treatment plants

Journal of Environmental Management ◽

10.1016/j.jenvman.2021.113270 ◽

2021 ◽

Vol 296 ◽

pp. 113270

Author(s):

Ranjith Kumar Manoharan ◽

Sathiyaraj Srinivasan ◽

Gnanendra Shanmugam ◽

Young-Ho Ahn

Keyword(s):

Antibiotic Resistance ◽

Wastewater Treatment ◽

Resistance Genes ◽

Wastewater Treatment Plants ◽

Antibiotic Resistance Genes ◽

Mobile Genetic Elements ◽

Full Scale ◽

Metagenomic Analysis ◽

Hospital Wastewater ◽

Genetic Elements

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Genetic analysis of a PER-2-producing Shewanella sp. strain harbouring a variety of mobile genetic elements and antibiotic resistance determinants

Journal of Global Antimicrobial Resistance ◽

10.1016/j.jgar.2017.06.005 ◽

2017 ◽

Vol 11 ◽

pp. 81-86 ◽

Cited By ~ 6

Author(s):

Marisa Almuzara ◽

Sabrina Montaña ◽

Terese Lazzaro ◽

Sylvia Uong ◽

Gisela Parmeciano Di Noto ◽

...

Keyword(s):

Antibiotic Resistance ◽

Genetic Analysis ◽

Mobile Genetic Elements ◽

Genetic Elements ◽

Resistance Determinants

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Identification of antibiotic resistance genes and associated mobile genetic elements in permafrost

Science China Life Sciences ◽

10.1007/s11427-020-1926-0 ◽

2021 ◽

Author(s):

Jian Cao ◽

Fei Liu ◽

Shuli Liu ◽

Jun Wang ◽

Baoli Zhu ◽

...

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Mobile Genetic Elements ◽

Genetic Elements

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Black Queen Evolution and Trophic Interactions Determine Plasmid Survival after the Disruption of the Conjugation Network

mSystems ◽

10.1128/msystems.00104-18 ◽

2018 ◽

Vol 3 (5) ◽

Cited By ~ 6

Author(s):

Johannes Cairns ◽

Katariina Koskinen ◽

Reetta Penttinen ◽

Tommi Patinen ◽

Anna Hartikainen ◽

...

Keyword(s):

Antibiotic Resistance ◽

Bacterial Communities ◽

Resistance Mechanism ◽

Real Life ◽

Ecological Factors ◽

Mobile Genetic Elements ◽

Resistance Mechanisms ◽

Antibiotics Resistance ◽

Bacterial Populations ◽

Genetic Elements

ABSTRACTMobile genetic elements such as conjugative plasmids are responsible for antibiotic resistance phenotypes in many bacterial pathogens. The ability to conjugate, the presence of antibiotics, and ecological interactions all have a notable role in the persistence of plasmids in bacterial populations. Here, we set out to investigate the contribution of these factors when the conjugation network was disturbed by a plasmid-dependent bacteriophage. Phage alone effectively caused the population to lose plasmids, thus rendering them susceptible to antibiotics. Leakiness of the antibiotic resistance mechanism allowing Black Queen evolution (i.e. a “race to the bottom”) was a more significant factor than the antibiotic concentration (lethal vs sublethal) in determining plasmid prevalence. Interestingly, plasmid loss was also prevented by protozoan predation. These results show that outcomes of attempts to resensitize bacterial communities by disrupting the conjugation network are highly dependent on ecological factors and resistance mechanisms.IMPORTANCEBacterial antibiotic resistance is often a part of mobile genetic elements that move from one bacterium to another. By interfering with the horizontal movement and the maintenance of these elements, it is possible to remove the resistance from the population. Here, we show that a so-called plasmid-dependent bacteriophage causes the initially resistant bacterial population to become susceptible to antibiotics. However, this effect is efficiently countered when the system also contains a predator that feeds on bacteria. Moreover, when the environment contains antibiotics, the survival of resistance is dependent on the resistance mechanism. When bacteria can help their contemporaries to degrade antibiotics, resistance is maintained by only a fraction of the community. On the other hand, when bacteria cannot help others, then all bacteria remain resistant. The concentration of the antibiotic played a less notable role than the antibiotic used. This report shows that the survival of antibiotic resistance in bacterial communities represents a complex process where many factors present in real-life systems define whether or not resistance is actually lost.

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