Assessment of global health risk of antibiotic resistance genes

Zhang, Zhenyan; Zhang, Qi; Wang, Tingzhang; Xu, Nuohan; Lu, Tao; Hong, Wenjie; Peñuelas, Josep; Gillings, Michael R.; Wang, Meixia; Gao, Wenwen; Qian, Haifeng

doi:10.1038/s41467-022-29283-8

Cited by 359 publications

(173 citation statements)

References 58 publications

Supporting

Mentioning

168

Contrasting

Unclassified

Order By: Relevance

“…MGEs carry non-essential genes that can provide their bacterial host with adaptive traits and alter their fitness, such as antimicrobial resistance (AMR) and virulence genes [18,19]. These elements apply a myriad of ecological and evolutionary strategies to promote their own replication and transmission, which allow them to persist even in the absence of positive selection for the beneficial genes they carry [20,21].…”

Section: Introductionmentioning

confidence: 99%

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

Botelho

Cazares

Schulenburg

2022

Preprint

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Botelho

Cazares

Schulenburg

2022

Preprint

View full text Add to dashboard Cite

show abstract

“…ARGs risk assessment and their hosts beyond "ESKAPE" pathogens ARGs health risk assessments were evaluated by four risk categories according to the omics-based framework from Rank I (the highest risk) to Rank IV (the lowest risk) based on risk indicators including human accessibility or human-associated-enrichment, gene mobility, and human pathogenicity [23,27]. It should be noted that the same ARG could be assessed in different health risk when the hosts are different, for example,10 tetL genes of tetracycline, belonging to the risk I to risk IV as well as unassessed categories (e.g., 2, 2, 1, and 5 genes belonged to risk I, risk III, risk IV, and unassessed categories, respectively), were identi ed, because 2 and 3 genes located in ESKAPE and non-ESKAPE pathogen bacteria, respectively, and the rest of 5 genes can not be assessed (Table S6).…”

Section: Discussionmentioning

confidence: 99%

“…3B). In particular, MDR harbored more than 70 subtypes multidrug resistance genes exhibiting diverse phenotypic in this study and might pose a health risk [27] (Table S5). More importantly, both rmicutes and proteobacteria could contribute to ARGs in this study (Fig.…”

Section: Analysis Of Args and Their Hostsmentioning

confidence: 95%

Antimicrobial resistance genes of fermented red pepper (FRP) related food in a large-scale environment: distribution pattern and risk assessment

Zhao

Dong

et al. 2022

Preprint

View full text Add to dashboard Cite

Background Antibiotic resistance genes (ARGs) are rapidly increasing numbers of difficult-to-treat infections and have been taken as a severe global health threat, which is estimated that the number of approximately 700,000 annual deaths and will exceed 10 million deaths per year by 2050 due to ARGs. Recently, ARGs involved in fermented foods have been taken more attention due to the spread of ARGs throughout the food chain. As well known, fermented red pepper (FRP) foods have been consumed widely as their unique flavor and health beneficial effects. However, knowledge gaps are still in the risk assessment of FRPs and their dissemination patterns on a large scale, which limited the development of effective methods to control and monitor the ARGs in fermented food. Here, a combination of read- and assembly-based whole genome sequencing methods as well as amplicon sequences analysis was used to investigate and reveal the ARGs dissemination patterns and risk assessment in FRPs related foods on a large-scale metagenomic data. Results 65.38% of FRP samples contained high-risk ARGs need to be concerned. Multidrug resistant (MDR) was the highest abundant type. On average, tetL and tetracycline resistance protein account for 81.8%, followed by multidrug (7.5%), beta-lactam (5.5%), colistin (1.5%), aminoglycoside (1.1%), and macrolide-lincosamide-streptogramin (1.1%) in the highest risk level, and the corresponding host range crossed from genus to bacteria indicating high mobility. Bacillus, Enterobacter, and Pantoea were the predominant host of carrying ARGs, which involved three major classes of resistance mechanism, that is, antibiotic efflux, antibiotic inactivation, and antibiotic target alteration. In addition, various ARGs and virulence factors with significant positive or negative relationships have been revealed. Conclusion Our findings demonstrated various ARGs were present in FRPs and high-risk ARGs such as tetL, tetracycline resistance protein, multidrug, beta-lactam, colistin, aminoglycoside, and macrolide-lincosamide-streptogramin has high mobility from genus to bacteria, which were significantly positively or negatively related to virulence factors. These results not only pave a way for understanding distribution patterns of ARGs in FRP foods on a large scale but also provide valuable knowledge to monitor and mitigate the ARGs.

show abstract

“…The emergence of resistance to antibiotics is the most challenging issue in the treatment of bacterial infections (Uddin et al, 2021). Antibiotic-resistant infections are widespread across the globe (Ventola, 2015; Zhang et al, 2022). Most bacteria might contain some form of antibiotic-resistant genes such as resistance plasmids or efflux pumps that might remain functionally silent until sufficiently challenged with selection pressure (Nikaido, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…The CARD web interface (https://card.mcmaster.ca/analyze/rgi) can quickly identify putative antibiotic-resistant genes based on numerous approaches such as BLAST, sequence alignment, regular expressions (RegEx), hidden Markov models (HMMs), and/or position-specific SNPs (Hendriksen et al, 2019). Each rickettsiae genome sequence was submitted to CARD’s resistance gene identifier (RGI) tool to generate annotation based on perfect, strict, and loose paradigm, and complete gene match criteria for the identification of putative antibiotic-resistant genes (Her et al, 2021; Kent et al, 2020; Zhang et al, 2022).…”

Section: Methodsmentioning

confidence: 99%

Prevalence and heterogeneity of antibiotic-resistant genes inOrientia tsutsugamushiand other rickettsial genomes

Rao

Ghate

Shastry

et al. 2022

Preprint

View full text Add to dashboard Cite

Despite a million infections every year and an estimated one billion people at risk, scrub typhus is regarded as a neglected tropical disease. The causative bacterium Orientia tsutsugamushi, a member of rickettsiae, seems to be intrinsically resistant to several classes of antibiotics. The emergence of antibiotic-resistant scrub typhus is likely to become a global public health concern. Yet, it is unknown as to how common antibiotic-resistant genes are in O. tsutsugamushi, and how variable these loci are among the genomes of rickettsiae. By using the comprehensive antibiotic resistance database, we explored 79 complete genomes from 24 species of rickettsiae for putative antibiotic-resistant loci. There were 244 unique antibiotic-resistant genes in rickettsiae. Both the total and unique antibiotic-resistant genes in O. tsutsugamushi were significantly less compared to other members of rickettsiae. However, antibiotic-resistant genes in O. tsutsugamushi genomes were more unique and highly variable. Many genes such as resistant versions of evgS, and vanS A/G were present in numerous copies. These results will have important implications in the context of antibiotic-resistant scrub typhus.

show abstract

Assessment of global health risk of antibiotic resistance genes

Cited by 359 publications

References 58 publications

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

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

Antimicrobial resistance genes of fermented red pepper (FRP) related food in a large-scale environment: distribution pattern and risk assessment

Prevalence and heterogeneity of antibiotic-resistant genes inOrientia tsutsugamushiand other rickettsial genomes

Contact Info

Product

Resources

About