What is a resistance gene? Ranking risk in resistomes

Martínez, José Luis; Coque, Teresa M.; Baquero, Fernando

doi:10.1038/nrmicro3399

Cited by 789 publications

(614 citation statements)

References 79 publications

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“…The distances of both the nearest ARGs and MRGs from the MGEs were much closer in bacteria from pathogen species and human habitat, reflecting the previous reported substantial capacity to develop resistance genes on MGEs in human pathogens (Perry and Wright, 2013;Gillings et al, 2015;Wales and Davies, 2015). Indeed, equipped on the proper transfer machinery, the efficient vehicles in gene shuffling, resistance gene dissemination can markedly be enhanced, benefiting the bacterial communities under environmental stress (Martinez et al, 2015;Soucy et al, 2015). Characterized by long exposure to selective pressure from antimicrobial and non-antimicrobial agents in human habitat, massive genetic exchanges have conferred efficient defense system to specific bacterial lineages (Jernberg et al, 2010;Juhas, 2015).…”

Section: Transfer Potential Of Args and Mrgssupporting

confidence: 55%

“…Therefore, by examining ARG-MRG coupling profile, we were prompted to ascertain whether there is a significant genome grouping pattern by ecologies. Co-occurrence of antibiotic and metal resistance genes L-G Li et al A significant genome cluster by habitats was observed (P-value o0.001, ANOISM; Supplementary Figure S8), suggesting that although interhabitat resistance gene transfer has frequently been detected (Martinez et al, 2015), these events have not homogenized the ARG-MRG coupling pattern among human, soil and water habitats. Instead, other ecological features among habitats might have a more substantial effect in shaping the resistome.…”

Section: Co-occurrence Between Args and Mrgsmentioning

confidence: 99%

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Co-occurrence of antibiotic and metal resistance genes revealed in complete genome collection

2016

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The high frequency of antibiotic resistance is a global public health concern. More seriously, widespread metal pressure in the environment may facilitate the proliferation of antibiotic resistance via coselection of antibiotic resistance genes (ARGs) and metal resistance genes (MRGs). Given the lack of comprehensive understanding of the ARG and MRG coselection, in this study both abundance relationship and genetic linkage between ARGs and MRGs were rigorously investigated by performing a genomic analysis of a large complete genome collection. Many more ARGs were enriched in human-associated bacteria compared with those subjected to less anthropogenic interference. The signatures of ARG and MRG co-occurrence were much more frequent and the distance linkages between ARGs and MRGs were much more intimate in human pathogens than those less human-associated bacteria. Moreover, the co-occurrence structures in the habitat divisions were significantly different, which could be attributed to their distinct gene transfer potentials. More exogenous ARGs and MRGs on the genomes of human pathogens indicated the importance of recent resistance acquisition in resistome development of human commensal flora. Overall, the study emphasizes the potential risk associated with ARG and MRG coselection of both environmental and medical relevance.

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Section: Transfer Potential Of Args and Mrgssupporting

confidence: 55%

Section: Co-occurrence Between Args and Mrgsmentioning

confidence: 99%

Co-occurrence of antibiotic and metal resistance genes revealed in complete genome collection

2016

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“…However, the less contribution of HGT through MGEs should not be overlooked, it should be emphasized instead, because the spread of ARGs through HGT had much higher risks than evolution of bacterial community (Martínez et al, 2015). The less contribution of MGEs might just indicate that the HGT through MGEs was not enough to obscure the significant correlation between evolution of ARGs and changes of bacterial community composition during sludge bio-drying.…”

Section: The Variation Of the Contributors To The Evolution Of Argsmentioning

confidence: 99%

Sludge bio-drying: Effective to reduce both antibiotic resistance genes and mobile genetic elements

et al. 2016

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a b s t r a c tSewage sludge is considered as one of major contributors to the increased environmental burden of ARGs. Sludge bio-drying was increasingly adopted due to its faster sludge reduction compared with composting. The fate of ARGs during full-scale sludge bio-drying was investigated to determine whether it could effectively reduce ARGs, and the contributions of bacterial community, horizontal gene transfer (HGT) through mobile genetic elements (MGEs) and co-selection from heavy metals to ARGs profiles were discussed in detail. Two piles with different aeration strategies (Pile I, the improved and Pile II, the control) were operated to elucidate effects of aeration strategy on ARGs profiles. Results showed that sludge bio-drying could effectively reduce both most of targeted ARGs (0.4e3.1 logs) and MGEs (0.8e3.3 logs) by the improved aeration strategy, which also enhanced both the sludge bio-drying performance and ARGs reduction. The enrichment of ARGs including ermF, tetX and sulII could be well explained by the evolution of bioavailable heavy metals, not HGT through MGEs, and their potential host bacteria mainly existed in Bacteroidetes. Although changes of bacterial community contributed the most to ARGs profiles, HGT through MGEs should be paid more attention especially in the thermophilic stage of sludge bio-drying.

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“…In recent years, the antibiotic resistome from both environmental and host-associated microbiomes has been explored (either function-or sequence-based), leading to the discovery of numerous ARGs (8,(12)(13)(14)(15). However, the risk of these identified ARGs has been considered to be overestimated because most studies have failed to differentiate between intrinsic ARGs and mobile ARGs (16). The mobile ARGs that are frequently as-sociated with mobile genetic elements (MGEs) and disseminated by HGT have been considered to have the highest risk of developing resistance among the antibiotic resistome (16).…”

mentioning

confidence: 99%

“…However, the risk of these identified ARGs has been considered to be overestimated because most studies have failed to differentiate between intrinsic ARGs and mobile ARGs (16). The mobile ARGs that are frequently as-sociated with mobile genetic elements (MGEs) and disseminated by HGT have been considered to have the highest risk of developing resistance among the antibiotic resistome (16).…”

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confidence: 99%

The Bacterial Mobile Resistome Transfer Network Connecting the Animal and Human Microbiomes

Yang

et al. 2016

Appl Environ Microbiol

278

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Horizontally acquired antibiotic resistance genes (ARGs) in bacteria are highly mobile and have been ranked as principal risk resistance determinants. However, the transfer network of the mobile resistome and the forces driving mobile ARG transfer are largely unknown. Here, we present the whole profile of the mobile resistome in 23,425 bacterial genomes and explore the effects of phylogeny and ecology on the recent transfer (>99% nucleotide identity) of mobile ARGs. We found that mobile ARGs are mainly present in four bacterial phyla and are significantly enriched in Proteobacteria. The recent mobile ARG transfer network, which comprises 703 bacterial species and 16,859 species pairs, is shaped by the bacterial phylogeny, while an ecological barrier also exists, especially when interrogating bacteria colonizing different human body sites. Phylogeny is still a driving force for the transfer of mobile ARGs between farm animals and the human gut, and, interestingly, the mobile ARGs that are shared between the human and animal gut microbiomes are also harbored by diverse human pathogens. Taking these results together, we suggest that phylogeny and ecology are complementary in shaping the bacterial mobile resistome and exert synergistic effects on the development of antibiotic resistance in human pathogens. IMPORTANCEThe development of antibiotic resistance threatens our modern medical achievements. The dissemination of antibiotic resistance can be largely attributed to the transfer of bacterial mobile antibiotic resistance genes (ARGs). Revealing the transfer network of these genes in bacteria and the forces driving the gene flow is of great importance for controlling and predicting the emergence of antibiotic resistance in the clinic. Here, by analyzing tens of thousands of bacterial genomes and millions of human and animal gut bacterial genes, we reveal that the transfer of mobile ARGs is mainly controlled by bacterial phylogeny but under ecological constraints. We also found that dozens of ARGs are transferred between the human and animal gut and human pathogens. This work demonstrates the whole profile of mobile ARGs and their transfer network in bacteria and provides further insight into the evolution and spread of antibiotic resistance in nature.A ntibiotic resistance is a growing global threat to human public health, and the continuing emergence of drug-resistant bacteria has led to the potential for a postantibiotic era (1). Bacteria have evolved a dynamic array of antimicrobial resistance mechanisms to withstand antibiotic attacks, such as altering drug target(s), synthesizing drug-inactivating enzymes, changing cell membrane permeability, and exporting drugs via efflux pumps (2). A large number of antibiotic resistance genes (ARGs) involved in these resistance mechanisms have been discovered and are collected in various ARG databases, including ARG-ANOTT (3), CARD (4), ResFinder (5), and ARDB (6). Because antibiotic resistance can be endogenous or exogenous, ARGs are generally classified as intrins...

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What is a resistance gene? Ranking risk in resistomes

Cited by 789 publications

References 79 publications

Co-occurrence of antibiotic and metal resistance genes revealed in complete genome collection

Co-occurrence of antibiotic and metal resistance genes revealed in complete genome collection

Sludge bio-drying: Effective to reduce both antibiotic resistance genes and mobile genetic elements

The Bacterial Mobile Resistome Transfer Network Connecting the Animal and Human Microbiomes

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