CD Genomics Blog

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When bacteria, fungi, viruses, and parasites change over time and no longer respond to antibiotics, antimicrobial resistance (AMR) occurs. This makes an emerging issue related to the development and usage of antibiotics. Traditional microbial screening methods for AMR can be very laborious and time-consuming. However, the use of next-generation sequencing (NGS), especially whole-genome sequencing (WGS), can efficiently determine the presence of certain ARGs in microorganisms, discover novel ARGs, determine mobile genetic elements that promote ARG transfer to other microorganisms, and evaluate the safety of bacteria. Knowledge about ARGs can help us understand how antibiotics work and how bacteria fight back. This knowledge contributes to a variety of practical applications, such as diagnostic testing, development of new antibiotics, management and modification of existing antibiotics, and discovery of factors that promote the emergence and replacement of pathogenic microorganisms.

NGS can offer different types of information that can acts as a guide to whether the infection is bacterial or viral; the type of bacteria, allowing the use of narrow-spectrum antimicrobials; the presence of genetic determinants of resistance; and, the predicted susceptibility of the isolate to antimicrobials. Additionally, the same diagnostics framework can provide information on many crucial aspects such as epidemiological typing for outbreak investigation, virulence factors of clinical relevance, and organism species. NGS technology offers mechanistic information about the resistance. Conventionally, phenotypic tests are used to provide information regarding resistance or susceptibility to antimicrobials. With its increasing affordability, NGS can complement phenotypic tests and reveal the molecular basis for this resistance/ susceptibility. The collected information can help identify the instances leading to resistance acquisition. Moreover, novel resistance mechanisms can be characterized by NGS when they arise, through sequencing of phenotypically resistant standard isolates.

In 2016, one of the last-resort antibiotics, colistin, had a form of resistance discovered that could be readily transferred to other bacteria. Annually, 25,000 deaths are reported due to the spread of multiple-drug resistant bacteria in Europe alone, a toll that is expected to increase. As a part of the management strategy, scientists and policy-makers formulated an NGS-based antibiotic resistance genes screening. NGS allows nucleic acids sequences to be generated much more cheaply and quickly than previously performed. NGS with the help of bioinformatics is a game-changer in the study of genomics and microbiology. It could provide a lot of information when applied to the antimicrobial resistance prediction of an unknown isolate or within an environmental sample.

In another study, NGS technology was able to identify the drug and species susceptibility profile of Mycobacterium tuberculosis with 93% accuracy while cutting the cost by 7% compared to routine clinical workflows. NGS results were also obtained faster than routine diagnosis. In outbreak scenarios, quick identification of the infecting pathogen is a key to outbreak containment. A study by Snitkin et al. achieved in 48 hours actionable reports, using NGS, of an unfolding vancomycin-resistant Enterococcus faecium outbreak. Rapid pathogen detection through NGS facilitates quicker intervention strategies, such as decolonization, patient isolation, or contact precautions. NGS also allows for possibly curtailing the spread and infection rates of high-risk organisms in healthcare settings. For example, NGS can be implemented to determine whether the same bacterial strain has spread causing an outbreak in a geographically distinct health care facility.

References:

  1. Tuan VP, Narith D, Tshibangu-Kabamba E, et al. A next-generation sequencing-based approach to identify genetic determinants of antibiotic resistance in Cambodian Helicobacter pylori clinical isolates. Journal of clinical medicine. 2019, 8(6).
  2. Angers A, Petrillo M, Patak A, et al. The role and implementation of nextgeneration sequencing technologies in the coordinated action plan against antimicrobial resistance. Publications Office of the European Union. 2017.
  3. Motro Y, Moran-Gilad J. Next-generation sequencing applications in clinical bacteriology. Biomolecular detection and quantification. 2017, 14.

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