The ESKAPE mobilome contributes to the spread of antimicrobial resistance and CRISPR-mediated conflict between mobile genetic elements

Mobile genetic elements (MGEs) mediate the shuffling of genes among organisms. They contribute to the spread of virulence and antibiotic resistance genes in human pathogens, including the particularly problematic group of ESKAPE pathogens, such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp. Here, we performed the first systematic analysis of MGEs, including plasmids, prophages, and integrative and conjugative/mobilizable elements (ICEs/IMEs), in the ESKAPE pathogens. We characterized over 1700 complete ESKAPE genomes and found that different MGE types are asymmetrically distributed across these pathogens. While some MGEs are capable of exchanging DNA beyond the genus (and phylum) barrier, horizontal gene transfer (HGT) is mainly restricted by phylum or genus. We further observed that most genes on MGEs have unknown functions and show intricate distribution patterns. Moreover, AMR genes and anti-CRISPRs are overrepresented in the ESKAPE mobilome. Our results also underscored species-specific trends shaping the number of MGEs, AMR, and virulence genes across pairs of conspecific ESKAPE genomes with and without CRISPR-Cas systems. Finally, we found that CRISPR targets vary according to MGE type: while plasmid CRISPRs almost exclusively target other plasmids, ICEs/IME CRISPRs preferentially target ICEs/IMEs and prophages. Overall, our study highlights the general importance of the ESKAPE mobilome in contributing to the spread of AMR and mediating conflict among MGEs.

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The shared resistome of human and pig microbiota is mobilized by distinct genetic elements

Applied and Environmental Microbiology ◽

10.1128/aem.01910-20 ◽

2020 ◽

Author(s):

Chao Wang ◽

Yuqin Song ◽

Na Tang ◽

Gang Zhang ◽

Sébastien Olivier Leclercq ◽

...

Keyword(s):

Antibiotic Resistance ◽

Intestinal Microbiota ◽

Resistance Genes ◽

Pathogenic Bacteria ◽

Antibiotic Resistance Genes ◽

Mobile Genetic Elements ◽

Human Pathogens ◽

Genetic Elements ◽

Metagenomics Data ◽

Genetic Context

The extensive use of antibiotics in hospitals and in the animal breeding industry has promoted antibiotic resistance in bacteria, which resulted in the emergence of a large number of antibiotic resistance genes in the intestinal tract of human and farmed animals. Genetic exchange of resistance genes between the two ecosystems is now well documented for pathogenic bacteria, but the repertoire of shared resistance genes in the commensal bacterial community and by which genetic modules they are disseminated are still unclear. By analyzing metagenomics data of human and pig intestinal samples both collected in Shenzhen, China, a set of 27 highly prevalent antibiotic resistance genes was found to be shared between human and pig intestinal microbiota. The mobile genetic context for 11 of these core antibiotic resistance genes could be identified by mining their carrying scaffolds constructed from the two datasets, leading to the detection of seven integrative and conjugative/mobilizable elements and two IS-related transposons. The comparison of the relative abundances between these detected mobile genetic elements and their associated antibiotic resistance genes revealed that for many genes, the estimated contribution of the mobile elements to the gene abundance differs strikingly depending on the host. These findings indicate that although some antibiotic resistance genes are ubiquitous across microbiota of human and pig populations, they probably relied on different genetic elements for their dissemination within each population. IMPORTANCE There is growing concern that antibiotic resistance genes could spread from the husbandry environment to human pathogens through dissemination mediated by mobile genetic elements. In this study, we investigated the contribution of mobile genetic elements to the abundance of highly prevalent antibiotic resistance genes found in commensal bacteria of both human and pig intestinal microbiota originating from the same region. Our results reveal that for most of these antibiotic resistance genes, the abundance is not explained by the same mobile genetic element in each host, suggesting that the human and pig microbial communities promoted a different set of mobile genetic carriers for the same antibiotic resistance genes. These results deepen our understanding of the dissemination of antibiotic resistance genes among and between human and pig gut microbiota.

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CRISPR-Cas is associated with fewer antibiotic resistance genes in bacterial pathogens

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2020.0464 ◽

2021 ◽

Vol 377 (1842) ◽

Author(s):

Elizabeth Pursey ◽

Tatiana Dimitriu ◽

Fernanda L. Paganelli ◽

Edze R. Westra ◽

Stineke van Houte

Keyword(s):

Antibiotic Resistance ◽

System Analysis ◽

Bacterial Pathogens ◽

Genetic Material ◽

Antibiotic Resistance Genes ◽

Mobile Genetic Elements ◽

Multidrug Resistant ◽

Human Pathogens ◽

Genetic Elements ◽

Defence System

The acquisition of antibiotic resistance (ABR) genes via horizontal gene transfer (HGT) is a key driver of the rise in multidrug resistance amongst bacterial pathogens. Bacterial defence systems per definition restrict the influx of foreign genetic material, and may therefore limit the acquisition of ABR. CRISPR-Cas adaptive immune systems are one of the most prevalent defences in bacteria, found in roughly half of bacterial genomes, but it has remained unclear if and how much they contribute to restricting the spread of ABR. We analysed approximately 40 000 whole genomes comprising the full RefSeq dataset for 11 species of clinically important genera of human pathogens, including Enterococcus , Staphylococcus , Acinetobacter and Pseudomonas . We modelled the association between CRISPR-Cas and indicators of HGT, and found that pathogens with a CRISPR-Cas system were less likely to carry ABR genes than those lacking this defence system. Analysis of the mobile genetic elements (MGEs) targeted by CRISPR-Cas supports a model where this host defence system blocks important vectors of ABR. These results suggest a potential ‘immunocompromised’ state for multidrug-resistant strains that may be exploited in tailored interventions that rely on MGEs, such as phages or phagemids, to treat infections caused by bacterial pathogens. This article is part of the theme issue ‘The secret lives of microbial mobile genetic elements’.

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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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Mobile Genetic Elements Drive the Antibiotic Resistome Alteration in Freshwater Shrimp Aquaculture

Water ◽

10.3390/w13111461 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1461

Author(s):

Hao Fang ◽

Nan Ye ◽

Kailong Huang ◽

Junnan Yu ◽

Shuai Zhang

Keyword(s):

Bacterial Communities ◽

High Throughput Sequencing ◽

Procambarus Clarkii ◽

Variation Partitioning ◽

Antibiotic Resistance Genes ◽

Mobile Genetic Elements ◽

Shrimp Aquaculture ◽

Sediment Samples ◽

Genetic Elements ◽

Freshwater Aquaculture

Shrimp aquaculture environments are a natural reservoir of multiple antibiotic resistance genes (ARGs) due to the overuse of antibiotics. Nowadays, the prevalence of these kinds of emerging contaminants in shrimp aquaculture environments is still unclear. In this study, high-throughput sequencing techniques were used to analyze the distribution of ARGs and mobile genetic elements (MGEs), bacterial communities, and their correlations in water and sediment samples in two types of typical shrimp (Procambarus clarkii and Macrobrachium rosenbergii) freshwater aquaculture environments. A total of 318 ARG subtypes within 19 ARG types were detected in all the samples. The biodiversity and relative abundance of ARGs in sediment samples showed much higher levels compared to water samples from all ponds in the study area. Bacitracin (17.44–82.82%) and multidrug (8.57–49.70%) were dominant ARG types in P. clarkii ponds, while sulfonamide (26.33–39.59%) and bacitracin (12.75–37.11%) were dominant ARG types in M. rosenbergii ponds. Network analysis underlined the complex co-occurrence patterns between bacterial communities and ARGs. Proteobacteria, Cyanobacteria, and Actinobacteria exhibited a high abundance in all samples, in which C39 (OTU25355) and Hydrogenophaga (OTU162961) played important roles in the dissemination of and variation in ARGs based on their strong connections between ARGs and bacterial communities. Furthermore, pathogens (e.g., Aeromonadaceae (OTU195200) and Microbacteriaceae (OTU16033)), which were potential hosts for various ARGs, may accelerate the propagation of ARGs and be harmful to human health via horizontal gene transfer mediated by MGEs. Variation partitioning analysis further confirmed that MGEs were the most crucial contributor (74.76%) driving the resistome alteration. This study may help us to understand the non-ignorable correlations among ARGs, bacterial diversity, and MGEs in the shrimp freshwater aquaculture environments.

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