Antimicrobial resistance (resistome) analysis

The development and spread of microbial antibiotic resistance causes previously reliable antibiotics to fail, posing serious global health concerns. Microbial communities respond to antibiotics not only by changing their composition, but also by acquiring and disseminating antibiotic resistance genes (ARGs). The resistome is the set of ARGs in a microbial community. 

Antimicrobial resistance is a serious global health problem that threatens our ability to effectively treat infections and is leading to increased morbidity, mortality, and healthcare costs. 

Microbial communities are heavily influenced by antibiotics. Microbiome compositions, both relative and absolute abundances, not only change, but species also respond to antibiotic treatments by acquiring and disseminating antibiotic resistance genes (ARGs). The emergence of antibiotic-resistant bacteria are rendering antimicrobial drugs ineffective in treating infections. This poses a significant threat to public health. 

Developing new antibiotics to combat these challenges is a complex and arduous task.  

We provide clients with detailed resistome analysis to enable insights on the antimicrobial resistance associated with new or already approved antimicrobial treatments or specific diseases. 

Our approach

We annotate our Clinical Microbiomics Human Microbiome Reference (HMR) for ARGs using the Comprehensive Antibiotic Resistance Database (CARD)¹, which is a manually curated and constantly updated collection of resistance genes, products, and associated phenotypes. 

We assign catalog genes to a CARD model by using the CARD Resistance Gene Identifier software (using DIAMOND as search method). First, our HMR catalog genes are translated into proteins and subsequently aligned to CARD ARG models. To avoid false ARG detections, we only include perfect matches to protein homolog models 

This technique allows detection of ARGs conferring resistance to the 21 most commonly used classes of antibiotics: Aminocyclitol, Aminoglycoside, Beta-lactam, Diaminopyrimidine, Fluoroquinolone, Fosfomycin, fusidic acids, Glycopeptide, Iminophenazine, Isoniazide, Lincosamide, Macrolide, Oxazolidinone, Phenicol, Pleuromutilin, Polymyxin, Rifamycin, Streptogramin, Sulfonamide, Tetracycline, and Multidrug efflux pumps (MEPs). 

ARG relative abundance is extracted from gene relative abundance, and we provide resistome analysis at the level of ARG richness, total ARG abundance, or ARG level. We aggregate the relative abundance of ARGs conferring resistance to each type of antibiotic to provide a resistome analysis at the level of antibiotic class. Furthermore, we summarize ARG relative abundance per resistance threat (e.g extended spectrum beta-lactam, carbapenem resistance, or vancomycin resistance). Finally, we mark which ARGs associated with disease or treatment have been seen in plasmids and/or pathogens to pinpoint the most threatening ARGs. 

Contact us to learn more about the applicability of resistome analysis to your study and further details about our methodology. 

References

¹ Alcock BP, Raphenya AR, Lau TTY, et al. CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database. Nucleic Acids Res. 2020 Jan 8;48(D1):D517-D525. doi: 10.1093/nar/gkz935.

 

Have a look at some of our published work involving resistome analyses:
Pallejá, A., Mikkelsen, K.H., Forslund, S.K. et al. Recovery of gut microbiota of healthy adults following antibiotic exposure. Nature Microbiology 3, 1255–1265 (2018). https://doi.org/10.1038/s41564-018-0257-9
Nielsen KL, Olsen MH, Pallejá A, et al. Microbiome Compositions and Resistome Levels after Antibiotic Treatment of Critically Ill Patients: An Observational Cohort Study. Microorganisms 12, 2542 (2021). doi: 10.3390/microorganisms9122542

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